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  <title type="text">PLoS Pathogens: New Articles</title>
  
  <author>
    <name>PLoS</name>
    <uri>http://www.plospathogens.org/</uri>
    <email>webmaster@plos.org</email>
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  <subtitle>Publishing science</subtitle>
  <id>info:doi/10.1371/feed.ppat</id>
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  <updated>2010-03-21T05:03:23Z</updated>
  <feedburner:info uri="plospathogens/newarticles" /><atom10:link xmlns:atom10="http://www.w3.org/2005/Atom" rel="hub" href="http://pubsubhubbub.appspot.com/" /><atom10:link xmlns:atom10="http://www.w3.org/2005/Atom" rel="self" type="application/atom+xml" href="http://pathogens.plosjournals.org/perlserv/?request=get-rss&amp;issn=1553-7374&amp;type=new-articles" /><feedburner:feedFlare href="http://add.my.yahoo.com/rss?url=http%3A%2F%2Fpathogens.plosjournals.org%2Fperlserv%2F%3Frequest%3Dget-rss%26issn%3D1553-7374%26type%3Dnew-articles" src="http://us.i1.yimg.com/us.yimg.com/i/us/my/addtomyyahoo4.gif">Subscribe with My Yahoo!</feedburner:feedFlare><feedburner:feedFlare href="http://www.newsgator.com/ngs/subscriber/subext.aspx?url=http%3A%2F%2Fpathogens.plosjournals.org%2Fperlserv%2F%3Frequest%3Dget-rss%26issn%3D1553-7374%26type%3Dnew-articles" src="http://www.newsgator.com/images/ngsub1.gif">Subscribe with NewsGator</feedburner:feedFlare><feedburner:feedFlare href="http://feeds.my.aol.com/add.jsp?url=http%3A%2F%2Fpathogens.plosjournals.org%2Fperlserv%2F%3Frequest%3Dget-rss%26issn%3D1553-7374%26type%3Dnew-articles" src="http://o.aolcdn.com/favorites.my.aol.com/webmaster/ffclient/webroot/locale/en-US/images/myAOLButtonSmall.gif">Subscribe with My AOL</feedburner:feedFlare><feedburner:feedFlare href="http://www.bloglines.com/sub/http://pathogens.plosjournals.org/perlserv/?request=get-rss&amp;issn=1553-7374&amp;type=new-articles" src="http://www.bloglines.com/images/sub_modern11.gif">Subscribe with Bloglines</feedburner:feedFlare><feedburner:feedFlare href="http://www.netvibes.com/subscribe.php?url=http%3A%2F%2Fpathogens.plosjournals.org%2Fperlserv%2F%3Frequest%3Dget-rss%26issn%3D1553-7374%26type%3Dnew-articles" src="http://www.netvibes.com/img/add2netvibes.gif">Subscribe with Netvibes</feedburner:feedFlare><feedburner:feedFlare href="http://fusion.google.com/add?feedurl=http%3A%2F%2Fpathogens.plosjournals.org%2Fperlserv%2F%3Frequest%3Dget-rss%26issn%3D1553-7374%26type%3Dnew-articles" src="http://buttons.googlesyndication.com/fusion/add.gif">Subscribe with Google</feedburner:feedFlare><feedburner:feedFlare href="http://www.pageflakes.com/subscribe.aspx?url=http%3A%2F%2Fpathogens.plosjournals.org%2Fperlserv%2F%3Frequest%3Dget-rss%26issn%3D1553-7374%26type%3Dnew-articles" src="http://www.pageflakes.com/ImageFile.ashx?instanceId=Static_4&amp;fileName=ATP_blu_91x17.gif">Subscribe with Pageflakes</feedburner:feedFlare><entry>
    <title>A Capsid-Encoded PPxY-Motif Facilitates Adenovirus Entry</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/HZftCgVX-W4/info%3Adoi%2F10.1371%2Fjournal.ppat.1000808" title="A Capsid-Encoded PPxY-Motif Facilitates Adenovirus Entry" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000808&amp;representation=XML" title="(XML) A Capsid-Encoded PPxY-Motif Facilitates Adenovirus Entry" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000808&amp;representation=PDF" title="(PDF) A Capsid-Encoded PPxY-Motif Facilitates Adenovirus Entry" />
    <author>
      <name>Harald Wodrich et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000808</id>
    <updated>2010-03-19T07:00:00Z</updated>
    <published>2010-03-19T07:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Viruses exploit cellular functions during entry and exit of cells. To redirect cellular functions for their own purpose, viruses encode high-affinity binding sites for key-cellular factors. One such domain is the PPxY motif, which is present in structural proteins of several, mainly enveloped viruses. This motif binds to ubiquitin ligases of the Nedd4 family and recruits their function to sites of virus budding from cells. Here we show that adenoviruses also encode a PPxY motif in the internal structural protein VI and that the PPxY motif has an unprecedented function in virus entry. Adenoviruses with mutations in the protein VI PPxY motif undergo normal endosomal uptake and membrane penetration but have reduced infectivity, altered intracellular targeting and lack efficient gene-delivery. We also find that protein VI is ubiquitylated by Nedd4 ligases in a PPxY dependent manner following partial capsid disassembly and displays rapid intracellular movement. Depletion of Nedd4 ligases also alters virus movement within cells during entry and reduces viral infectivity. Given that PPxY motifs are important for virus exit our findings might have uncovered an additional function for PPxY motifs in virus entry, potentially expanding the significance of PPxY motifs and functionally related domains for viral replication.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/HZftCgVX-W4" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000808</feedburner:origLink></entry>
  <entry>
    <title>The Essentials of Protein Import in the Degenerate Mitochondrion of Entamoeba histolytica</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/asfl65El2_s/info%3Adoi%2F10.1371%2Fjournal.ppat.1000812" title="The Essentials of Protein Import in the Degenerate Mitochondrion of Entamoeba histolytica" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000812&amp;representation=PDF" title="(PDF) The Essentials of Protein Import in the Degenerate Mitochondrion of Entamoeba histolytica" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000812&amp;representation=XML" title="(XML) The Essentials of Protein Import in the Degenerate Mitochondrion of Entamoeba histolytica" />
    <author>
      <name>Pavel Dolezal et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000812</id>
    <updated>2010-03-19T07:00:00Z</updated>
    <published>2010-03-19T07:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;All eukaryotic organisms have mitochondria, organelles cordoned by a double membrane, which are descendants of an ancestral bacterial endosymbiont. Nowadays, mitochondria are fully integrated into the context of diverse cellular processes and serve in providing energy, iron-containing prosthetic groups and some of the cellular building blocks like lipids and amino acids. In multi-cellular organisms, mitochondria play an additional vital role in cell signaling pathways and programmed cell death. In some unicellular eukaryotes which inhabit oxygen poor environments, intriguing mitochondrial adaptations have taken place resulting in the creation of specialized compartments known as mitosomes and hydrogenosomes. Several important human pathogens like &lt;i&gt;Entamoeba histolytica&lt;/i&gt;, &lt;i&gt;Giardia intestinalis&lt;/i&gt;, &lt;i&gt;Trichomonas vaginalis&lt;/i&gt; and microsporidia contain these organelles and in many cases the function and biogenesis of these organelles remain unknown. In this paper, we investigated the protein import pathways into the mitosomes of &lt;i&gt;E. histolytica&lt;/i&gt;, which represent one of the simplest mitochondria-related compartment discovered yet. In accordance with the limited organellar proteome, we show that only core components of mitochondria-related protein import machines are present in &lt;i&gt;E. histolytica&lt;/i&gt; to serve for the import of a small set of substrate proteins.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/asfl65El2_s" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000812</feedburner:origLink></entry>
  <entry>
    <title>Human Cytomegalovirus Protein pUL117 Targets the Mini-Chromosome Maintenance Complex and Suppresses Cellular DNA Synthesis</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/9FoXSEzgjlQ/info%3Adoi%2F10.1371%2Fjournal.ppat.1000814" title="Human Cytomegalovirus Protein pUL117 Targets the Mini-Chromosome Maintenance Complex and Suppresses Cellular DNA Synthesis" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000814&amp;representation=PDF" title="(PDF) Human Cytomegalovirus Protein pUL117 Targets the Mini-Chromosome Maintenance Complex and Suppresses Cellular DNA Synthesis" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000814&amp;representation=XML" title="(XML) Human Cytomegalovirus Protein pUL117 Targets the Mini-Chromosome Maintenance Complex and Suppresses Cellular DNA Synthesis" />
    <author>
      <name>Zhikang Qian et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000814</id>
    <updated>2010-03-19T07:00:00Z</updated>
    <published>2010-03-19T07:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Inhibition of host DNA synthesis is pivotal for many viruses to establish productive infection and cause disease. Human cytomegalovirus (HCMV) is the top viral cause of birth defects in newborns and leads to life-threatening diseases in individuals with compromised immunity. HCMV blocks host DNA synthesis and creates a cellular environment to replicate its own genome. We report here that pUL117, a novel viral protein that we recently identified, is required for HCMV to block host DNA synthesis. Mechanistically, pUL117 is necessary and sufficient to reduce the accumulation of the mini-chromosome maintenance (MCM) complex, a replicative helicase that unwinds the origin and initiates cellular DNA replication. During HCMV infection pUL117 may also have a direct role in preventing MCM loading onto chromatin. Importantly, knockdown of MCM proteins restored the ability of pUL117-deficient virus to block cellular DNA synthesis. Thus, targeting MCM function is a mechanism for pUL117 to help block cellular DNA synthesis during HCMV infection. Several proteins encoded by other viruses have also been reported to subvert MCM function by distinct mechanisms and inhibit host DNA synthesis when over-expressed in host cells. Therefore, MCM has emerged as a conserved target for viruses to prevent host DNA synthesis. Our results illustrate a novel strategy that HCMV uses to manipulate this critical cellular factor during infection. This study helps to elucidate the sophisticated strategies used by a large DNA virus to modulate cellular processes to promote infection and pathogenesis and may also shed light on the regulation of eukaryotic DNA replication.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/9FoXSEzgjlQ" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000814</feedburner:origLink></entry>
  <entry>
    <title>Differential Regulation of Effector- and Central-Memory Responses to Toxoplasma gondii Infection by IL-12 Revealed by Tracking of Tgd057-Specific CD8+ T Cells</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/bfe3hwbr1d4/info%3Adoi%2F10.1371%2Fjournal.ppat.1000815" title="Differential Regulation of Effector- and Central-Memory Responses to Toxoplasma gondii Infection by IL-12 Revealed by Tracking of Tgd057-Specific CD8+ T Cells" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000815&amp;representation=PDF" title="(PDF) Differential Regulation of Effector- and Central-Memory Responses to Toxoplasma gondii Infection by IL-12 Revealed by Tracking of Tgd057-Specific CD8+ T Cells" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000815&amp;representation=XML" title="(XML) Differential Regulation of Effector- and Central-Memory Responses to Toxoplasma gondii Infection by IL-12 Revealed by Tracking of Tgd057-Specific CD8+ T Cells" />
    <author>
      <name>Douglas C. Wilson et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000815</id>
    <updated>2010-03-19T07:00:00Z</updated>
    <published>2010-03-19T07:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;&lt;i&gt;Toxoplasma gondii&lt;/i&gt; is a ubiquitous protozoan parasite that causes severe disease in people with compromised immune function. It is known that CD8+ T cells are essential for the establishment of protective immunity, primarily through the delivery of the effector cytokine interferon-γ (IFN-γ) to &lt;i&gt;Toxoplasma&lt;/i&gt;-infected cells. However, it remains unclear how memory CD8+ T cells develop in response to &lt;i&gt;Toxoplasma&lt;/i&gt; infection, and to what extent inflammatory cytokines like interleukin-12 (IL-12) play a role in memory development. Furthermore, the natural &lt;i&gt;T. gondii&lt;/i&gt; antigens that induce CD8+ T cell activation have not yet been fully uncovered. Using new technology for the screening of antigen specificity, we discovered the first natural antigen-specific CD8+ T cell population induced by &lt;i&gt;T. gondii&lt;/i&gt; infection in C57BL/6 mice. By tracking natural parasite-specific responses, we found that IL-12 plays a vital role in promoting the development of IFN-γ-producing effector memory CD8+ T cells but at a cost to the numbers and function of central memory CD8+ T cells.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/bfe3hwbr1d4" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000815</feedburner:origLink></entry>
  <entry>
    <title>A Combination of Independent Transcriptional Regulators Shapes Bacterial Virulence Gene Expression during Infection</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/S3H6DW6fmT4/info%3Adoi%2F10.1371%2Fjournal.ppat.1000817" title="A Combination of Independent Transcriptional Regulators Shapes Bacterial Virulence Gene Expression during Infection" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000817&amp;representation=PDF" title="(PDF) A Combination of Independent Transcriptional Regulators Shapes Bacterial Virulence Gene Expression during Infection" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000817&amp;representation=XML" title="(XML) A Combination of Independent Transcriptional Regulators Shapes Bacterial Virulence Gene Expression during Infection" />
    <author>
      <name>Samuel A. Shelburne et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000817</id>
    <updated>2010-03-19T07:00:00Z</updated>
    <published>2010-03-19T07:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Group A &lt;i&gt;Streptococcus&lt;/i&gt; (GAS) causes diverse infections in humans ranging from pharyngitis (strep throat) to necrotizing fasciitis (the flesh-eating disease). It is well known that GAS secretes a broad array of virulence factors that are critical to its ability to cause human infections, but how GAS coordinates virulence factor production during infection is poorly understood. We discovered that two GAS proteins, &lt;u&gt;c&lt;/u&gt;atabolite &lt;u&gt;c&lt;/u&gt;ontrol &lt;u&gt;p&lt;/u&gt;rotein &lt;u&gt;A&lt;/u&gt; (CcpA) and &lt;u&gt;c&lt;/u&gt;ontrol &lt;u&gt;o&lt;/u&gt;f &lt;u&gt;v&lt;/u&gt;irulence &lt;u&gt;r&lt;/u&gt;egulator (CovR), regulate production of many of the same virulence factor encoding genes, indicating that GAS uses these two regulatory proteins to modulate virulence factor production in response to environmental stimuli. We determined that CcpA and CovR are able to bind to DNA from co-regulated genes, indicating that the proteins control gene expression by directly interacting with DNA. Using a mouse model of muscle infection, we found that CcpA and CovR, alone and in combination, are critical to the ability of GAS to regulate expression of virulence factor encoding genes during infection. These findings increase understanding regarding the regulatory mechanisms critical to the ability of bacterial pathogens to cause infection.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/S3H6DW6fmT4" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000817</feedburner:origLink></entry>
  <entry>
    <title>Nucleophosmin Phosphorylation by v-Cyclin-CDK6 Controls KSHV Latency</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/2Q4Pw0wE9AU/info%3Adoi%2F10.1371%2Fjournal.ppat.1000818" title="Nucleophosmin Phosphorylation by v-Cyclin-CDK6 Controls KSHV Latency" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000818&amp;representation=XML" title="(XML) Nucleophosmin Phosphorylation by v-Cyclin-CDK6 Controls KSHV Latency" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000818&amp;representation=PDF" title="(PDF) Nucleophosmin Phosphorylation by v-Cyclin-CDK6 Controls KSHV Latency" />
    <author>
      <name>Grzegorz Sarek et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000818</id>
    <updated>2010-03-19T07:00:00Z</updated>
    <published>2010-03-19T07:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Latency is the predominant mode of viral persistence in KS and PEL tumors, and has a fundamental impact on KSHV tumorigenesis. Establishment and maintenance of latency involves a number of viral and cellular factors. This study provides a novel functional link between LANA and v-cyclin by showing that phosphorylation of nucleophosmin (NPM) by the v-cyclin-CDK6 kinase complex supports its interaction with LANA, and thus enables the transcriptional silencing of KSHV lytic genes needed for latency. These findings indicate that KSHV has evolved mechanisms to utilize host proteins for maintaining the latency, and underscores the role of NPM as a regulator of not only mammalian transcription but also of viral transcription. Taken together, our data suggests that a cellular protein, NPM, is a critical factor for the latency of this oncogenic human virus, and may thus represent an attractive novel target for intervention.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/2Q4Pw0wE9AU" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000818</feedburner:origLink></entry>
  <entry>
    <title>Helicobacter pylori Lipopolysaccharide Is Synthesized via a Novel Pathway with an Evolutionary Connection to Protein N-Glycosylation</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/YS-5o6DB1wY/info%3Adoi%2F10.1371%2Fjournal.ppat.1000819" title="Helicobacter pylori Lipopolysaccharide Is Synthesized via a Novel Pathway with an Evolutionary Connection to Protein N-Glycosylation" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000819&amp;representation=XML" title="(XML) Helicobacter pylori Lipopolysaccharide Is Synthesized via a Novel Pathway with an Evolutionary Connection to Protein N-Glycosylation" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000819&amp;representation=PDF" title="(PDF) Helicobacter pylori Lipopolysaccharide Is Synthesized via a Novel Pathway with an Evolutionary Connection to Protein N-Glycosylation" />
    <author>
      <name>Isabelle Hug et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000819</id>
    <updated>2010-03-19T07:00:00Z</updated>
    <published>2010-03-19T07:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Bacterial surfaces are decorated with glycans. The human stomach pathogen &lt;i&gt;Helicobacter pylori&lt;/i&gt; exposes lipopolysaccharide (LPS) containing Lewis antigens that mimic human glycan structures. &lt;i&gt;H. pylori&lt;/i&gt; alters its Lewis antigen display in adaptation to the individual host. Lewis antigens can interact with human dendritic cells, thereby inducing a suppression of the immune response and facilitating a chronic &lt;i&gt;H. pylori&lt;/i&gt; infection. Whereas three general LPS biosynthesis pathways are known, the route of LPS assembly in &lt;i&gt;H. pylori&lt;/i&gt; remained to be elucidated. We identified and characterized two components of the &lt;i&gt;H. pylori&lt;/i&gt; LPS pathway, WecA and WaaL, which demonstrated that, as in other bacteria, the glycan is initially assembled onto a polyprenoid lipid carrier. This intermediate then has to cross a membrane barrier, requiring specialized translocases. &lt;i&gt;H. pylori&lt;/i&gt; does not employ a translocase from common LPS pathways. We show that instead &lt;i&gt;H. pylori&lt;/i&gt; uses a translocase named Wzk, which is involved in protein &lt;i&gt;N&lt;/i&gt;-glycosylation in other bacteria. Wzk was able to translocate various glycan structures. The identification of Wzk as the &lt;i&gt;H. pylori&lt;/i&gt; translocase involved in LPS biosynthesis indicates an evolutionary connection between LPS and glycoprotein biosynthesis pathways.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/YS-5o6DB1wY" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000819</feedburner:origLink></entry>
  <entry>
    <title>MicroRNA Antagonism of the Picornaviral Life Cycle: Alternative Mechanisms of Interference</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/gC-MIlBcc-w/info%3Adoi%2F10.1371%2Fjournal.ppat.1000820" title="MicroRNA Antagonism of the Picornaviral Life Cycle: Alternative Mechanisms of Interference" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000820&amp;representation=XML" title="(XML) MicroRNA Antagonism of the Picornaviral Life Cycle: Alternative Mechanisms of Interference" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000820&amp;representation=PDF" title="(PDF) MicroRNA Antagonism of the Picornaviral Life Cycle: Alternative Mechanisms of Interference" />
    <author>
      <name>Elizabeth J. Kelly et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000820</id>
    <updated>2010-03-19T07:00:00Z</updated>
    <published>2010-03-19T07:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Virus host range is shaped by cellular determinants such as transcription factors and receptor expression. In addition, we have previously shown that tissue-specific microRNAs can be utilized to direct the specificity of a replication competent picornavirus, Coxsackievirus A21. In this report, we demonstrate the mechanism by which microRNAs are able to directly influence oncolytic viruses, an important class of anticancer agents. We show that microRNA expression is an important determinant of permissivity to oncolytic virus replication, but the actual abundance of that expression is far more important. In addition, we show that there are actually multiple different stages in the life cycle of a replication competent picornavirus that are amenable to regulation by cellular microRNAs. We proceed to illustrate that microRNAs can regulate virus tropism in vivo, but demonstrate that circulating high viral titers in the blood can overcome this mechanism of conferring tissue specificity. MicroRNAs are well known to have both oncogenic or oncosuppressive activities in human cancers. Here, we show that tissue-specific microRNA expression can also be used to modulate the efficacy of viral anticancer therapeutics, and the mechanism by which they are able to do so.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/gC-MIlBcc-w" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000820</feedburner:origLink></entry>
  <entry>
    <title>Natural Strain Variation and Antibody Neutralization of Dengue Serotype 3 Viruses</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/40f1c2sm7JQ/info%3Adoi%2F10.1371%2Fjournal.ppat.1000821" title="Natural Strain Variation and Antibody Neutralization of Dengue Serotype 3 Viruses" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000821&amp;representation=PDF" title="(PDF) Natural Strain Variation and Antibody Neutralization of Dengue Serotype 3 Viruses" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000821&amp;representation=XML" title="(XML) Natural Strain Variation and Antibody Neutralization of Dengue Serotype 3 Viruses" />
    <author>
      <name>Wahala M. P. B. Wahala et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000821</id>
    <updated>2010-03-19T07:00:00Z</updated>
    <published>2010-03-19T07:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Dengue viruses are mosquito-borne flaviviruses and the agents of dengue fever and dengue hemorrhagic fever. It has been widely assumed that antibodies that neutralize dengue bind to regions on the viral envelope (E) protein that are conserved within each serotype. However, few studies have explored how natural variation influences dengue-antibody interactions. Mouse antibodies that strongly neutralize dengue bind to a region on domain III of E protein. This region has been the focus of much recent work because it might be the target of protective human antibodies as well. We compared a large number of E protein sequences and discovered that the region on E protein domain III targeted by neutralizing antibodies was highly variable between strains of dengue serotype 3. Using a panel of antibodies, we experimentally demonstrate that natural strain variation in dengue serotype 3 has a strong influence on antibody binding and neutralization. Our results challenge the dogma that neutralizing antibody binding regions are conserved within each serotype. The results of this study are relevant to the current global effort to develop and evaluate dengue vaccines.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/40f1c2sm7JQ" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000821</feedburner:origLink></entry>
  <entry>
    <title>Inhibition of Host Vacuolar H+-ATPase Activity by a Legionella pneumophila Effector</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/1oYDsk0FvD4/info%3Adoi%2F10.1371%2Fjournal.ppat.1000822" title="Inhibition of Host Vacuolar H+-ATPase Activity by a Legionella pneumophila Effector" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000822&amp;representation=PDF" title="(PDF) Inhibition of Host Vacuolar H+-ATPase Activity by a Legionella pneumophila Effector" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000822&amp;representation=XML" title="(XML) Inhibition of Host Vacuolar H+-ATPase Activity by a Legionella pneumophila Effector" />
    <author>
      <name>Li Xu et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000822</id>
    <updated>2010-03-19T07:00:00Z</updated>
    <published>2010-03-19T07:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;One hallmark of the lysosome is a low luminal pH that is important for its maturation as well as the activity of many hydrolyzing enzymes responsible for efficient digestion of phagocytosed contents. To survive and replicate in phagocytes, successful intracellular pathogens have evolved various mechanisms to circumvent the challenges posed by lysosomal killing. One salient feature associated with infection of the intracellular bacterial pathogen &lt;i&gt;Legionella pneumophila&lt;/i&gt; is the maintenance of a neutral pH of the Legionella containing vacuoles (LCVs) that supports its intracellular growth in the early phase of infection, while the nonpathogenic mutants are believed to be immediately trafficked to an acidic compartment. In eukaryotic cells, organelle acidification is mediated by the vacuolar H&lt;sup&gt;+&lt;/sup&gt;-ATPase that translocates protons into target compartments in a process energized by ATP hydrolysis. The recent discovery of the association of v-ATPase with LCVs points to the necessity for active modulation of v-ATPase activity by the bacterium. By screening &lt;i&gt;L. pneumophila&lt;/i&gt; proteins that cause a yeast phenotype similar to its v-ATPase mutants, we have identified a substrate of the &lt;i&gt;L. pneumophila&lt;/i&gt; Dot/Icm type IV secretion system that specifically inhibits the activity of the proton transporter. This protein, termed SidK, inhibits the activity of v-ATPase by directly interacting with the VatA subunit that is responsible for hydrolyzing ATP. Moreover, macrophages harboring SidK display defects in phagosomal acidification and lysosomal killing of non-pathogenic bacteria. We also found that expression of &lt;i&gt;sidK&lt;/i&gt; is highly induced right after stationary bacteria are diluted into fresh medium, suggesting that SidK plays an important role in the early phase of infection. Our results reveal a mechanism by which an intravacuolar pathogen engages the v-ATPase protein and inhibits its activity, rather than actively avoiding its association with the pathogen's vacuolar membrane.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/1oYDsk0FvD4" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000822</feedburner:origLink></entry>
  <entry>
    <title>The Human Polyoma JC Virus Agnoprotein Acts as a Viroporin</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/sYrM_VqAaog/info%3Adoi%2F10.1371%2Fjournal.ppat.1000801" title="The Human Polyoma JC Virus Agnoprotein Acts as a Viroporin" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000801&amp;representation=XML" title="(XML) The Human Polyoma JC Virus Agnoprotein Acts as a Viroporin" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000801&amp;representation=PDF" title="(PDF) The Human Polyoma JC Virus Agnoprotein Acts as a Viroporin" />
    <author>
      <name>Tadaki Suzuki et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000801</id>
    <updated>2010-03-12T08:00:00Z</updated>
    <published>2010-03-12T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Most non-enveloped viruses exit their host cells following cell lysis, which involves breakdown of the cell membrane and death of the host cell, and which is presumably the final result of an increase in plasma membrane permeability. JC virus (JCV) is the causative agent of progressive multifocal leukoencephalopathy (PML) and belongs to the polyomavirus family, which have non-enveloped virions. The extracellular release of mature progeny polyomavirus virions has been suggested to occur when cells disintegrate or rupture; however, the molecular mechanism(s) employed by JCV to induce cell lysis and facilitate virion release remain elusive. Viroporins are a group of proteins that modify the permeability of cellular membranes and promote the release of viral particles from infected cells. These proteins are not essential for the replication of viruses, but their presence often enhances virus growth. Here, we demonstrate that the JCV agnoprotein forms homo-oligomers as an integral membrane protein and acts as a viroporin, and that expression of agnoprotein results in plasma membrane permeabilization and virion release. These observations suggest that the process of virion release of this non-enveloped DNA virus is highly regulated by a single viral protein.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/sYrM_VqAaog" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000801</feedburner:origLink></entry>
  <entry>
    <title>Membrane Damage Elicits an Immunomodulatory Program in Staphylococcus aureus</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/kFYO3BmfnSY/info%3Adoi%2F10.1371%2Fjournal.ppat.1000802" title="Membrane Damage Elicits an Immunomodulatory Program in Staphylococcus aureus" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000802&amp;representation=PDF" title="(PDF) Membrane Damage Elicits an Immunomodulatory Program in Staphylococcus aureus" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000802&amp;representation=XML" title="(XML) Membrane Damage Elicits an Immunomodulatory Program in Staphylococcus aureus" />
    <author>
      <name>Ahmed S. Attia et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000802</id>
    <updated>2010-03-12T08:00:00Z</updated>
    <published>2010-03-12T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;&lt;i&gt;Staphylococcus aureus&lt;/i&gt; infects almost every tissue within the human body utilizing a range of virulence factors to combat host defenses. The expression of these virulence factors is a tightly regulated process; however, the signals sensed by &lt;i&gt;S. aureus&lt;/i&gt; during infection remain elusive. It has been hypothesized that heme toxicity is a signal sensed by &lt;i&gt;S. aureus&lt;/i&gt; during infection. This hypothesis is based on the observation that &lt;i&gt;S. aureus&lt;/i&gt; mutants which are incapable of relieving heme-toxicity due to inactivation of the ATPase HrtA elicit an immunomodulatory program that interferes with neutrophil recruitment to the site of infection. In keeping with this, &lt;i&gt;S. aureus hrtA&lt;/i&gt; mutants exhibit liver-specific hypervirulence. Herein, we provide evidence for an alternative model to explain the hypervirulent phenotype of &lt;i&gt;S. aureus ΔhrtA&lt;/i&gt;. We demonstrate that instead of accumulation of heme toxicity being the trigger for the observed immunomodulatory program, dysregulated pore formation caused by the HrtB permease triggers the anti-neutrophil response. In support of this model, over-expression of HrtB in wildtype &lt;i&gt;S. aureus&lt;/i&gt; or exposing &lt;i&gt;S. aureus&lt;/i&gt; to channel-forming antimicrobial peptides induces a similar immunomodulatory program. Our work provides evidence that &lt;i&gt;S. aureus&lt;/i&gt; senses membrane damage and induces an immunomodulatory circuit that helps the pathogen evade immune-mediated clearance.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/kFYO3BmfnSY" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000802</feedburner:origLink></entry>
  <entry>
    <title>YfiBNR Mediates Cyclic di-GMP Dependent Small Colony Variant Formation and Persistence in Pseudomonas aeruginosa</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/kCXu0kf7yyE/info%3Adoi%2F10.1371%2Fjournal.ppat.1000804" title="YfiBNR Mediates Cyclic di-GMP Dependent Small Colony Variant Formation and Persistence in Pseudomonas aeruginosa" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000804&amp;representation=PDF" title="(PDF) YfiBNR Mediates Cyclic di-GMP Dependent Small Colony Variant Formation and Persistence in Pseudomonas aeruginosa" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000804&amp;representation=XML" title="(XML) YfiBNR Mediates Cyclic di-GMP Dependent Small Colony Variant Formation and Persistence in Pseudomonas aeruginosa" />
    <author>
      <name>Jacob G. Malone et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000804</id>
    <updated>2010-03-12T08:00:00Z</updated>
    <published>2010-03-12T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;During long-term chronic infections of cystic fibrosis patients, &lt;i&gt;Pseudomonas aeruginosa&lt;/i&gt; adapts to the lung environment, generating various different morphotypes including small colony variants (SCVs), small, strongly adherent colonies whose appearance correlates with persistence of infection. The SCV morphology is strongly associated with increased levels of the signaling molecule cyclic di-GMP. In this study we investigated the connection between cyclic di-GMP, SCV and persistence of infection. Following a genetic screen for mutants that displayed SCV morphologies, we identified and characterized the YfiBNR system. YfiN is a membrane-bound cyclic di-GMP producing enzyme, whose activity is tightly controlled by YfiR and YfiB. Cyclic di-GMP produced by YfiN boosts exopolysaccharide synthesis, generating an SCV morphotype upon YfiR-mediated release of YfiN repression. The resulting YfiN-mediated SCV morphotype is highly resistant to macrophage phagocytosis &lt;i&gt;in vitro&lt;/i&gt;, suggesting a role for the SCV phenotype in immune system evasion. Consistent with this, YfiN de-repression increased the persistence of &lt;i&gt;P. aeruginosa&lt;/i&gt; in long-term infections in a mouse model. The observation that the addition of antibiotics decreased the number of suppressors, and the relative fitness disadvantage of the YfiN-mediated SCV morphotype in liquid culture, suggested that SCV-mediated persistence might be favored during antimicrobial chemotherapy.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/kCXu0kf7yyE" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000804</feedburner:origLink></entry>
  <entry>
    <title>Dynamic Imaging of Experimental Leishmania donovani-Induced Hepatic Granulomas Detects Kupffer Cell-Restricted Antigen Presentation to Antigen-Specific CD8+ T Cells</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/SxtDZ8wJKG0/info%3Adoi%2F10.1371%2Fjournal.ppat.1000805" title="Dynamic Imaging of Experimental Leishmania donovani-Induced Hepatic Granulomas Detects Kupffer Cell-Restricted Antigen Presentation to Antigen-Specific CD8+ T Cells" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000805&amp;representation=PDF" title="(PDF) Dynamic Imaging of Experimental Leishmania donovani-Induced Hepatic Granulomas Detects Kupffer Cell-Restricted Antigen Presentation to Antigen-Specific CD8+ T Cells" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000805&amp;representation=XML" title="(XML) Dynamic Imaging of Experimental Leishmania donovani-Induced Hepatic Granulomas Detects Kupffer Cell-Restricted Antigen Presentation to Antigen-Specific CD8+ T Cells" />
    <author>
      <name>Lynette Beattie et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000805</id>
    <updated>2010-03-12T08:00:00Z</updated>
    <published>2010-03-12T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;&lt;i&gt;Leishmania donovani&lt;/i&gt; is a protozoan parasite that causes severe disease in humans with associated pathology in the spleen and liver. In experimental models of &lt;i&gt;L. donovani&lt;/i&gt; infection, the hepatic response to infection is characterised by the presence of a focal mononuclear cell-rich inflammatory response (a granuloma) surrounding cells infected with intracellular amastigotes. Granulomas provide focus to the ensuing immune response, helping to contain parasite dissemination and providing the major effector site responsible for parasites elimination from the liver. Although granulomas are believed to form around infected resident liver macrophages (Kupffer cells), the role of these cells in intra-granuloma antigen presentation is currently unknown. As CD8&lt;sup&gt;+&lt;/sup&gt; T cells have been shown to play an important role in hepatic resistance to &lt;i&gt;L. donovani&lt;/i&gt; following natural infection, vaccination and during immunotherapy, we asked which cells within the granuloma microenvironment serve as targets for antigen recognition by effector CD8&lt;sup&gt;+&lt;/sup&gt; T cells. Here we provide evidence that the heavily infected mononuclear cell core of the granuloma is composed almost entirely of Kupffer cells, many having migrated from the surrounding sinusoids. Furthermore, by intra-vital 2-photon microscopy, we show that only Kupffer cells laden with intracellular amastigotes are able to form long-lasting antigen-specific interactions with CD8&lt;sup&gt;+&lt;/sup&gt; T cells within the granuloma microenvironment. These data have important implications for the understanding of how granulomas function to limit infection and may have important implications for the development of vaccines to &lt;i&gt;Leishmania&lt;/i&gt; that are designed to induce CD8&lt;sup&gt;+&lt;/sup&gt; T cell responses.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/SxtDZ8wJKG0" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000805</feedburner:origLink></entry>
  <entry>
    <title>N-Acetylglucosamine Induces White to Opaque Switching, a Mating Prerequisite in Candida albicans</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/XQdDh-k9RQU/info%3Adoi%2F10.1371%2Fjournal.ppat.1000806" title="N-Acetylglucosamine Induces White to Opaque Switching, a Mating Prerequisite in Candida albicans" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000806&amp;representation=XML" title="(XML) N-Acetylglucosamine Induces White to Opaque Switching, a Mating Prerequisite in Candida albicans" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000806&amp;representation=PDF" title="(PDF) N-Acetylglucosamine Induces White to Opaque Switching, a Mating Prerequisite in Candida albicans" />
    <author>
      <name>Guanghua Huang et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000806</id>
    <updated>2010-03-12T08:00:00Z</updated>
    <published>2010-03-12T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;To mate, the human fungal pathogen &lt;i&gt;Candida albicans&lt;/i&gt; must undergo a complex phenotypic change from a round “white” to large, elongated “opaque” cell. This involves the regulation of approximately 5% of the organism's genes. Surprisingly, this complex transition is not required for mating in other related yeast. Even more surprisingly, it was found that &lt;i&gt;in vitro&lt;/i&gt; the mating-competent opaque phenotype was unstable at 37°C, the temperature of the host body. This observation led to a paradox. If &lt;i&gt;C. albicans&lt;/i&gt; lives primarily in an animal host, physiological temperature would thwart mating, so where does &lt;i&gt;C. albicans&lt;/i&gt; mate? This led to the suggestion that some physiological condition in the host niche stabilizes the opaque phenotype or even induces switching from white to opaque, so cells can mate. Recently, we demonstrated that the high concentrations of CO&lt;sub&gt;2&lt;/sub&gt; found in tissue and the gastrointestinal tract induced switching from white to opaque and then stabilized the opaque phenotype. Here, we demonstrate that a second factor, N-acetylglucosamine (GlcNAc), a sugar released primarily by bacteria in the gastrointestinal tract, also induces the switch from white to opaque and stabilizes the opaque phenotype. We demonstrate by mutational analysis that GlcNAc induction is regulated primarily by the Ras1/cAMP pathway, which also regulates filamentation of &lt;i&gt;C. albicans&lt;/i&gt;. This is perhaps not surprising given that white-opaque switching shares with filamentation several phenotypic characteristics. Finally, we show that induction by GlcNAc requires the phosphorylated master switch gene that regulates spontaneous switching, suggesting that it induces the switch from white to opaque by activating the gene product of the master switch gene. Together, our results suggest that multiple signals from bacterial co-members of the gastrointestinal tract microbiota regulate switching and, therefore, mating of &lt;i&gt;C. albicans&lt;/i&gt; in the colonized host.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/XQdDh-k9RQU" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000806</feedburner:origLink></entry>
  <entry>
    <title>Structural Basis of Cell Wall Cleavage by a Staphylococcal Autolysin</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/dazf-tWo4zw/info%3Adoi%2F10.1371%2Fjournal.ppat.1000807" title="Structural Basis of Cell Wall Cleavage by a Staphylococcal Autolysin" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000807&amp;representation=XML" title="(XML) Structural Basis of Cell Wall Cleavage by a Staphylococcal Autolysin" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000807&amp;representation=PDF" title="(PDF) Structural Basis of Cell Wall Cleavage by a Staphylococcal Autolysin" />
    <author>
      <name>Sebastian Zoll et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000807</id>
    <updated>2010-03-12T08:00:00Z</updated>
    <published>2010-03-12T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Although Staphylococci are common habitants of the human skin and the respiratory tract, a number of highly pathogenic strains are a major cause of hospital-associated infections and can be life threatening especially in immunocompromised patients. Moreover, an increasing number of strains has acquired resistance against commonly used antibiotics, which makes treatment of infections a challenge. Therefore, antibacterial drugs that act on new targets are needed to counteract the further spread of multiresistent staphylococci. The autolysins, which are cell wall associated enzymes that are essential for cell proliferation, represent one promising such new target. We used x-ray crystallography to solve the structure of a catalytically active region of the autolysin of &lt;i&gt;Staphylococcus epidermidis&lt;/i&gt;, AmiE, at atomic resolution. Our studies reveal a defined binding groove for a specific cell wall component on the protein surface. Using &lt;i&gt;in silico&lt;/i&gt; calculations in combination with biochemical studies, we are able to identify key motifs that are required for the recognition of the cell wall by autolysins. Our data further indicate that, besides these core motifs, species-specific alterations of bacterial cell walls are responsible for the unambiguous identification of ligands. Knowledge of the interactions in an enzyme-substrate complex, as well as information about the mechanism of catalysis, are prerequisites for the successful development of antimicrobial drugs. Our results therefore provide a platform from which a new class of inhibitors can be launched.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/dazf-tWo4zw" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000807</feedburner:origLink></entry>
  <entry>
    <title>Staphylococcus aureus RNAIII Binds to Two Distant Regions of coa mRNA to Arrest Translation and Promote mRNA Degradation</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/Lj8N9v4d2Cg/info%3Adoi%2F10.1371%2Fjournal.ppat.1000809" title="Staphylococcus aureus RNAIII Binds to Two Distant Regions of coa mRNA to Arrest Translation and Promote mRNA Degradation" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000809&amp;representation=XML" title="(XML) Staphylococcus aureus RNAIII Binds to Two Distant Regions of coa mRNA to Arrest Translation and Promote mRNA Degradation" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000809&amp;representation=PDF" title="(PDF) Staphylococcus aureus RNAIII Binds to Two Distant Regions of coa mRNA to Arrest Translation and Promote mRNA Degradation" />
    <author>
      <name>Clément Chevalier et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000809</id>
    <updated>2010-03-12T08:00:00Z</updated>
    <published>2010-03-12T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;&lt;i&gt;Staphylococcus aureus&lt;/i&gt; causes a wide spectrum of diseases in humans and is one of the main causes of community- as well as hospital-acquired infections. &lt;i&gt;S. aureus&lt;/i&gt; produces a large number of virulence factors that are expressed in a coordinated manner and at appropriate time and space. To this end, a set of multiple &lt;i&gt;trans&lt;/i&gt;-acting regulators, including regulatory proteins and RNA, is brought into play. The ability of organisms to use RNA to modulate gene expression is a relatively new concept. This is the case for the largest regulatory RNA, &lt;i&gt;S. aureus&lt;/i&gt; RNAIII, which controls the switch between the expression of surface proteins and excreted toxins. Here we used a combination of approaches &lt;i&gt;in vivo&lt;/i&gt; and &lt;i&gt;in vitro&lt;/i&gt; to analyze the mechanism used by RNAIII to regulate the expression of one major virulence factor, staphylocoagulase, which promotes clotting of human plasma. We found that RNAIII regulates the expression of staphylocoagulase through direct interactions with its mRNA. RNAIII binds to two distant regions of &lt;i&gt;coa&lt;/i&gt; mRNA to arrest translation and in a coordinated manner, the endoribonuclease III recognizes the formed duplex to initiate degradation of the repressed mRNA. Staphylocoagulase belongs to the early expressed virulence factors, such as protein A, that are repressed by RNAIII using a similar dual mechanism. This study illustrates the diversity of RNAIII-mRNA topologies and how these multiple RNAIII-mRNA interactions would mediate virulence regulation.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/Lj8N9v4d2Cg" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000809</feedburner:origLink></entry>
  <entry>
    <title>Homeostatic Interplay between Bacterial Cell-Cell Signaling and Iron in Virulence</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/fWAqPYfqJiw/info%3Adoi%2F10.1371%2Fjournal.ppat.1000810" title="Homeostatic Interplay between Bacterial Cell-Cell Signaling and Iron in Virulence" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000810&amp;representation=PDF" title="(PDF) Homeostatic Interplay between Bacterial Cell-Cell Signaling and Iron in Virulence" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000810&amp;representation=XML" title="(XML) Homeostatic Interplay between Bacterial Cell-Cell Signaling and Iron in Virulence" />
    <author>
      <name>Ronen Hazan et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000810</id>
    <updated>2010-03-12T08:00:00Z</updated>
    <published>2010-03-12T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Bacterial cells can communicate with one another about their surrounding environment. This information can be in the form of small self-secreted molecules acting as signals to activate or inhibit the expression of genes. &lt;i&gt;Pseudomonas aeruginosa&lt;/i&gt; is an environmental bacterium that infects diverse organisms from plants to humans. Our results show that this pathogen uses two highly sensitive networks, namely MvfR and LasR/RhlR pathways, to modulate its virulence functions by titrating the concentration of the small molecules HHQ and PQS in a manner that depends upon the presence or absence of iron. Via negative and positive feedback loops, this bacterium processes the signaled information to regulate its virulence functions and homeostatically balance the production of the small molecules required for the activation of the MvfR virulence network. Our study sheds light on paradigmatic complex networks that maintain a homeostatic bacterial virulence response.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/fWAqPYfqJiw" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000810</feedburner:origLink></entry>
  <entry>
    <title>Direct TLR2 Signaling Is Critical for NK Cell Activation and Function in Response to Vaccinia Viral Infection</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/OK5KirrUoM0/info%3Adoi%2F10.1371%2Fjournal.ppat.1000811" title="Direct TLR2 Signaling Is Critical for NK Cell Activation and Function in Response to Vaccinia Viral Infection" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000811&amp;representation=PDF" title="(PDF) Direct TLR2 Signaling Is Critical for NK Cell Activation and Function in Response to Vaccinia Viral Infection" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000811&amp;representation=XML" title="(XML) Direct TLR2 Signaling Is Critical for NK Cell Activation and Function in Response to Vaccinia Viral Infection" />
    <author>
      <name>Jennifer Martinez et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000811</id>
    <updated>2010-03-12T08:00:00Z</updated>
    <published>2010-03-12T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;NK cells are an important component of innate immunity in fighting against poxviral infections in vivo. However, how NK cells are activated and exert their function in controlling poxviruses remains poorly understood. In this paper, we found that VV, the most studied member of the poxvirus family, could directly activate TLR2 on NK cells and that the direct TLR2 stimulation was critical for NK cell activation and function in the control of VV infection in vivo. We further showed that TLR2-dependent NK cell activation by VV was mediated through the PI3K-ERK pathway. In addition, we demonstrated that the activating receptor NKG2D was also required for efficient NK cell activation and function. Collectively, these results represent the first evidence that direct TLR signaling is crucial to NK cell activation and function in the control of a viral infection in vivo, indicate that multiple pathways are required for efficient NK cell activation, and may provide important insights into the design of effective strategies to combat poxviral infections.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/OK5KirrUoM0" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000811</feedburner:origLink></entry>
  <entry>
    <title>Innate Killing of Leishmania donovani by Macrophages of the Splenic Marginal Zone Requires IRF-7</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/b97k4uaYPME/info%3Adoi%2F10.1371%2Fjournal.ppat.1000813" title="Innate Killing of Leishmania donovani by Macrophages of the Splenic Marginal Zone Requires IRF-7" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000813&amp;representation=XML" title="(XML) Innate Killing of Leishmania donovani by Macrophages of the Splenic Marginal Zone Requires IRF-7" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000813&amp;representation=PDF" title="(PDF) Innate Killing of Leishmania donovani by Macrophages of the Splenic Marginal Zone Requires IRF-7" />
    <author>
      <name>Rebecca Phillips et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000813</id>
    <updated>2010-03-12T08:00:00Z</updated>
    <published>2010-03-12T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Macrophages are phagocytic cells that play a dual role in infection. They can kill ingested micro-organisms and thus help eliminate the threat from infection, but some pathogens have adapted to survive within macrophages and use the intracellular niche they provide as a means of immune evasion. Although it has long been recognised that macrophages in different tissues look and behave differently, this heterogeneity is rarely taken into account when examining macrophage-pathogen interactions. By comparing gene expression profiles of different types of macrophages, we show here the diversity of the macrophage response to &lt;i&gt;Leishmania donovani&lt;/i&gt; infection. In one cell line that resembles the macrophages of the spleen that are targets of &lt;i&gt;L. donovani&lt;/i&gt; infection, we identified a gene expression signature more similar to that expected for a viral infection, and by using RNAi, identified that the transcription factor IRF-7 played an essential role in the selective capacity of these macrophages to kill this intracellular parasite. The importance of this pathway of host resistance was directly confirmed by examining the response of splenic macrophages in &lt;i&gt;Irf-7&lt;/i&gt;-deficient mice. This comparative approach has, therefore, identified a new molecular pathway involved in the innate tissue-specific control of &lt;i&gt;L. donovani&lt;/i&gt; infection.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/b97k4uaYPME" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000813</feedburner:origLink></entry>
  <entry>
    <title>Direct Restriction of Virus Release and Incorporation of the Interferon-Induced Protein BST-2 into HIV-1 Particles</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/HvAcal3JNf0/info%3Adoi%2F10.1371%2Fjournal.ppat.1000701" title="Direct Restriction of Virus Release and Incorporation of the Interferon-Induced Protein BST-2 into HIV-1 Particles" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000701&amp;representation=PDF" title="(PDF) Direct Restriction of Virus Release and Incorporation of the Interferon-Induced Protein BST-2 into HIV-1 Particles" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000701&amp;representation=XML" title="(XML) Direct Restriction of Virus Release and Incorporation of the Interferon-Induced Protein BST-2 into HIV-1 Particles" />
    <author>
      <name>Kathleen Fitzpatrick et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000701</id>
    <updated>2010-03-05T08:00:00Z</updated>
    <published>2010-03-05T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;The cellular protein BST-2 prevents newly formed particles of HIV-1 and other enveloped viruses from escaping the infected cell by an unclear mechanism. Here, we show that BST-2 is appropriately positioned to directly retain newly formed HIV-1 virions on the cell surface and is incorporated into infectious virions. We suggest that the incorporation of BST-2 into virions is a key aspect of the protein's broadly restrictive activity against enveloped viruses.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/HvAcal3JNf0" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000701</feedburner:origLink></entry>
  <entry>
    <title>Limited Trafficking of a Neurotropic Virus Through Inefficient Retrograde Axonal Transport and the Type I Interferon Response</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/fHwEemEbTPc/info%3Adoi%2F10.1371%2Fjournal.ppat.1000791" title="Limited Trafficking of a Neurotropic Virus Through Inefficient Retrograde Axonal Transport and the Type I Interferon Response" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000791&amp;representation=PDF" title="(PDF) Limited Trafficking of a Neurotropic Virus Through Inefficient Retrograde Axonal Transport and the Type I Interferon Response" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000791&amp;representation=XML" title="(XML) Limited Trafficking of a Neurotropic Virus Through Inefficient Retrograde Axonal Transport and the Type I Interferon Response" />
    <author>
      <name>Karen Z. Lancaster et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000791</id>
    <updated>2010-03-05T08:00:00Z</updated>
    <published>2010-03-05T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Neurotropic viruses, including herpesviruses, rabies virus, and poliovirus, initiate infection in the periphery and can move through peripheral neurons to reach the central nervous system (CNS). Since peripheral neurons can be up to one meter long, inefficient neural transport could dramatically affect pathogenesis of neurotropic viruses. In this study, we used a novel viral “bar-coding” assay to quantify the efficiency of poliovirus transport from the periphery to the CNS using a mouse model. Only 20% of the poliovirus population successfully moved from the periphery to the CNS. We discovered that transport of poliovirus in peripheral neurons was very inefficient, and the innate immune response also limited viral movement. Surprisingly, the neural transport barrier was as strong as the innate immune response barrier. Importantly, by overcoming both the neural transport and innate immune barriers, 80% of the poliovirus population successfully moved from the periphery to the CNS, and mice succumbed to disease three times faster than mice with intact barriers. This study identifies inefficient neural transport as a substantial barrier to viral movement in peripheral neurons, which may limit CNS access for many viruses.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/fHwEemEbTPc" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000791</feedburner:origLink></entry>
  <entry>
    <title>Endocytosis of the Anthrax Toxin Is Mediated by Clathrin, Actin and Unconventional Adaptors</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/bqIa-vfUw44/info%3Adoi%2F10.1371%2Fjournal.ppat.1000792" title="Endocytosis of the Anthrax Toxin Is Mediated by Clathrin, Actin and Unconventional Adaptors" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000792&amp;representation=XML" title="(XML) Endocytosis of the Anthrax Toxin Is Mediated by Clathrin, Actin and Unconventional Adaptors" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000792&amp;representation=PDF" title="(PDF) Endocytosis of the Anthrax Toxin Is Mediated by Clathrin, Actin and Unconventional Adaptors" />
    <author>
      <name>Laurence Abrami et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000792</id>
    <updated>2010-03-05T08:00:00Z</updated>
    <published>2010-03-05T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;&lt;i&gt;Bacillus anthracis&lt;/i&gt; is the bacterium responsible for the anthrax disease. Its virulence is mainly due to 2 factors, the anthrax toxin and the anti-phagocytic capsule. This toxin is composed of three independent polypeptide chains. Two of these have enzymatic activity and are responsible for the effects of the toxin. The third has no activity but is absolutely required to bring the 2 enzymatic subunits into the cell where they act. If one blocks entry into the cells, one blocks the effects of these toxins, which is why it is important to understand how the toxin enters into the cell at the molecular level. Here we identified various molecules that are involved in efficiently bringing the toxin into the cell. First, we found that the actin cytoskeleton plays an important role in organizing one of the two anthrax toxin receptors at the cell surface. Second, we found a cytosolic protein, β-arrestin, that is required to modify the intracellular part of the toxin receptor, to allow uptake. Finally, we directly show, for the first time, that anthrax toxin uptake is mediated by the so-called clathrin-dependent pathway, a very modular entry pathway, but that the toxin utilizes this pathway in an unconventional way.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/bqIa-vfUw44" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000792</feedburner:origLink></entry>
  <entry>
    <title>Tsetse EP Protein Protects the Fly Midgut from Trypanosome Establishment</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/_UezTcnryhQ/info%3Adoi%2F10.1371%2Fjournal.ppat.1000793" title="Tsetse EP Protein Protects the Fly Midgut from Trypanosome Establishment" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000793&amp;representation=XML" title="(XML) Tsetse EP Protein Protects the Fly Midgut from Trypanosome Establishment" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000793&amp;representation=PDF" title="(PDF) Tsetse EP Protein Protects the Fly Midgut from Trypanosome Establishment" />
    <author>
      <name>Lee R. Haines et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000793</id>
    <updated>2010-03-05T08:00:00Z</updated>
    <published>2010-03-05T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;In Africa, tsetse flies transmit the trypanosomes causing the devastating diseases sleeping sickness in man and nagana in domesticated animals. These diseases are major causes of underdevelopment in Africa. Paradoxically, most, but not all, flies are resistant to infection with trypanosomes, but we do not have a clear picture of how flies fight off trypanosomes. Here we show that a particular, tsetse-specific immune responsive protein called tsetse EP acts as a powerful antagonist of trypanosome establishment in the fly midgut. It is known that starvation of flies leads to an increase in their susceptibility to trypanosomes and this may be a considerable factor in the epidemiology of the disease in Africa. Here we demonstrate that starvation leads to a decrease in tsetse EP levels, which may explain how starvation of the fly works to increase its susceptibility.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/_UezTcnryhQ" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000793</feedburner:origLink></entry>
  <entry>
    <title>Direct Visualization by Cryo-EM of the Mycobacterial Capsular Layer: A Labile Structure Containing ESX-1-Secreted Proteins</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/TOG4quBcCus/info%3Adoi%2F10.1371%2Fjournal.ppat.1000794" title="Direct Visualization by Cryo-EM of the Mycobacterial Capsular Layer: A Labile Structure Containing ESX-1-Secreted Proteins" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000794&amp;representation=PDF" title="(PDF) Direct Visualization by Cryo-EM of the Mycobacterial Capsular Layer: A Labile Structure Containing ESX-1-Secreted Proteins" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000794&amp;representation=XML" title="(XML) Direct Visualization by Cryo-EM of the Mycobacterial Capsular Layer: A Labile Structure Containing ESX-1-Secreted Proteins" />
    <author>
      <name>Musa Sani et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000794</id>
    <updated>2010-03-05T08:00:00Z</updated>
    <published>2010-03-05T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;The genus &lt;i&gt;Mycobacterium&lt;/i&gt; contains a number of important pathogens, such as &lt;i&gt;Mycobacterium tuberculosis&lt;/i&gt;. The highly characteristic cell envelope of these bacteria plays a crucial role in the infection process. The most apparent difference with other bacteria is the recently described outer membrane composed of unique (glyco)lipids. However, on top of this membrane mycobacteria also have an ill-defined capsular layer. In this paper, we studied this capsular layer using different electron microscopy techniques and mass spectrometry. Using close to native state preparation method, we show that both pathogenic and non-pathogenic mycobacteria have a labile capsular layer that covers the outer membrane. This capsular layer, in addition to containing arabinogalactan, glycan and mannose-containing glyco-lipids, also surprisingly contains a large amount of ESX-1-secreted proteins in &lt;i&gt;Mycobacterium marinum&lt;/i&gt;. Furthermore, we also show that the capsule plays a role in the binding of macrophages and the induction of cytokines. Collectively, these results show for the first time that the capsule can be visualized on both pathogenic and non-pathogenic mycobacteria. In addition, growing mycobacteria under standard laboratory conditions in the presence of detergent with agitation promotes capsular shedding and influences the biological characteristics of the bacteria.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/TOG4quBcCus" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000794</feedburner:origLink></entry>
  <entry>
    <title>Fine-Tuning Translation Kinetics Selection as the Driving Force of Codon Usage Bias in the Hepatitis A Virus Capsid</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/1E2rka3n1sA/info%3Adoi%2F10.1371%2Fjournal.ppat.1000797" title="Fine-Tuning Translation Kinetics Selection as the Driving Force of Codon Usage Bias in the Hepatitis A Virus Capsid" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000797&amp;representation=PDF" title="(PDF) Fine-Tuning Translation Kinetics Selection as the Driving Force of Codon Usage Bias in the Hepatitis A Virus Capsid" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000797&amp;representation=XML" title="(XML) Fine-Tuning Translation Kinetics Selection as the Driving Force of Codon Usage Bias in the Hepatitis A Virus Capsid" />
    <author>
      <name>Lluís Aragonès et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000797</id>
    <updated>2010-03-05T08:00:00Z</updated>
    <published>2010-03-05T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Each organism has a specific codon usage signature. Translational selection i.e., selection for the codon adaptation to the tRNA pools, is one of the driving forces of codon bias. In the virus world, this implies an adjustment of the virus codon usage to that of the host cell. Hepatitis A virus appears as an exception to the rule, with a highly deoptimized codon usage, suggesting that translational selection is not the underlying mechanism of its codon bias. However, since the virus lacks a mechanism of cellular protein synthesis inhibition, the deoptimized codon usage may be envisaged as a hawk (cell) and dove (hepatitis A virus) competition strategy for tRNAs and translational selection as well. To confirm this possibility, we artificially induced cell protein synthesis shut-off, thus increasing the tRNA pool availability for the virus, and we took advantage of the quasispecies dynamics to elucidate changes in its codon usage. Virus adaptation to the drug results in a re-deoptimization of codon usage in the capsid region, suggesting a requirement of a slow translation rate, i.e., a translation kinetic selection, instead of a translational selection associated with an optimization of the codon usage. Translation kinetics control is based on the right combination of codons (common and rare) that allows a regulated ribosome traffic rate ensuring the proper protein folding. Capsid folding is critical for a virus transmitted through the fecal-oral route with long extracorporeal periods.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/1E2rka3n1sA" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000797</feedburner:origLink></entry>
  <entry>
    <title>Perforin and IL-2 Upregulation Define Qualitative Differences among Highly Functional Virus-Specific Human CD8+ T Cells</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/t5sfySuEaJY/info%3Adoi%2F10.1371%2Fjournal.ppat.1000798" title="Perforin and IL-2 Upregulation Define Qualitative Differences among Highly Functional Virus-Specific Human CD8+ T Cells" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000798&amp;representation=XML" title="(XML) Perforin and IL-2 Upregulation Define Qualitative Differences among Highly Functional Virus-Specific Human CD8+ T Cells" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000798&amp;representation=PDF" title="(PDF) Perforin and IL-2 Upregulation Define Qualitative Differences among Highly Functional Virus-Specific Human CD8+ T Cells" />
    <author>
      <name>George Makedonas et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000798</id>
    <updated>2010-03-05T08:00:00Z</updated>
    <published>2010-03-05T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Although CD8&lt;sup&gt;+&lt;/sup&gt; T cells are thought to be largely responsible for the control of viral infections, exactly how they mediate protection is uncertain. One approach to assessing their protective capacity is to measure several of their functions simultaneously. Generally, it is believed the more functions a cell can perform, the better its potential to control viral replication. A multi-functional response including interleukin-2 (IL-2) production is currently valued as the key correlate of protection. We recently characterized a novel CD8&lt;sup&gt;+&lt;/sup&gt; T cell function: rapid perforin upregulation, which serves to contribute to and sustain the killing of virally infected host cells. In this study, we show that new perforin is abundant during adenovirus and cytomegalovirus infections, but scarcely detected in the context of influenza and Epstein-Barr virus. Importantly, perforin and IL-2 are rarely co-expressed. The significance of this relationship is that we can no longer assume the more functions a CD8&lt;sup&gt;+&lt;/sup&gt; T cell performs in response to a virus the better. Thus, when considering vaccine design, no single functional profile will likely be protective across all pathogens. Rather, vaccine-induced T cell responses may need to be “pathogen-specific”, as different T cell functional responses will be important for controlling different viral infections.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/t5sfySuEaJY" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000798</feedburner:origLink></entry>
  <entry>
    <title>Kaposi's Sarcoma-Associated Herpesvirus ORF57 Protein Binds and Protects a Nuclear Noncoding RNA from Cellular RNA Decay Pathways</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/sS7-xI9IpFQ/info%3Adoi%2F10.1371%2Fjournal.ppat.1000799" title="Kaposi's Sarcoma-Associated Herpesvirus ORF57 Protein Binds and Protects a Nuclear Noncoding RNA from Cellular RNA Decay Pathways" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000799&amp;representation=PDF" title="(PDF) Kaposi's Sarcoma-Associated Herpesvirus ORF57 Protein Binds and Protects a Nuclear Noncoding RNA from Cellular RNA Decay Pathways" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000799&amp;representation=XML" title="(XML) Kaposi's Sarcoma-Associated Herpesvirus ORF57 Protein Binds and Protects a Nuclear Noncoding RNA from Cellular RNA Decay Pathways" />
    <author>
      <name>Brooke B. Sahin et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000799</id>
    <updated>2010-03-05T08:00:00Z</updated>
    <published>2010-03-05T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;In order to replicate efficiently, a virus must ensure that its genes are properly expressed in the context of an infected host cell. Recent work has demonstrated that eukaryotic cells have RNA quality control pathways that degrade improperly processed, aberrant RNAs. Our published findings using an unusual Kaposi's sarcoma-associated herpesvirus (KSHV) nuclear RNA, called PAN RNA, have suggested that intronless polyadenylated transcripts are subject to such a quality control system. Because most KSHV genes lack introns, we hypothesized that KSHV must have evolved mechanisms that bypass this quality control system. In support of this idea, we show that the ORF57 protein, a multifunctional enhancer of KSHV gene expression, binds to and stabilizes PAN RNA. We further define an element called the ORF57-responsive element (ORE) in PAN RNA that is necessary for ORF57-binding and activity on PAN RNA. In addition, we show that the ORE is sufficient to confer ORF57-responsiveness to a heterologous intronless mRNA, but not its spliced counterpart. These observations substantiate the model that ORF57 enhances KSHV gene expression by protecting viral transcripts from host RNA surveillance pathways. More broadly, these data suggest that viruses producing intronless nuclear RNAs require mechanisms to evade host quality control mechanisms.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/sS7-xI9IpFQ" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000799</feedburner:origLink></entry>
  <entry>
    <title>Fatal Transmissible Amyloid Encephalopathy: A New Type of Prion Disease Associated with Lack of Prion Protein Membrane Anchoring</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/jePkL-jRq1o/info%3Adoi%2F10.1371%2Fjournal.ppat.1000800" title="Fatal Transmissible Amyloid Encephalopathy: A New Type of Prion Disease Associated with Lack of Prion Protein Membrane Anchoring" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000800&amp;representation=XML" title="(XML) Fatal Transmissible Amyloid Encephalopathy: A New Type of Prion Disease Associated with Lack of Prion Protein Membrane Anchoring" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000800&amp;representation=PDF" title="(PDF) Fatal Transmissible Amyloid Encephalopathy: A New Type of Prion Disease Associated with Lack of Prion Protein Membrane Anchoring" />
    <author>
      <name>Bruce Chesebro et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000800</id>
    <updated>2010-03-05T08:00:00Z</updated>
    <published>2010-03-05T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Prion diseases, also known as transmissible spongiform encephalopathies, are infectious fatal neurodegenerative diseases of humans and animals. A major feature of prion diseases is the refolding and aggregation of a normal host protein, prion protein (PrP), into a disease-associated form which may contribute to brain damage. In uninfected individuals, normal PrP is anchored to the outer cell membrane by a sugar-phosphate-lipid linker molecule. In the present report we show that prion infection of mice expressing PrP lacking the anchor can result in a new type of fatal neurodegenerative disease. This disease displays mechanisms of damage to brain cells and brain blood vessels found in Alzheimer's disease and in familial amyloid brain diseases. In contrast, the typical sponge-like brain damage seen in prion diseases was not observed. These results suggest that presence or absence of PrP membrane anchoring can influence the type of neurodegeneration seen after prion infection.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/jePkL-jRq1o" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000800</feedburner:origLink></entry>
  <entry>
    <title>PLoS Pathogens Issue Image | Vol. 6(2) February 2010</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/ALR76MR9nks/info%3Adoi%2F10.1371%2Fimage.ppat.v06.i02" title="PLoS Pathogens Issue Image | Vol. 6(2) February 2010" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/image.ppat.v06.i02&amp;representation=XML" title="(XML) PLoS Pathogens Issue Image | Vol. 6(2) February 2010" />
    <id>info:doi/10.1371/image.ppat.v06.i02</id>
    <updated>2010-02-26T08:00:00Z</updated>
    <published>2010-02-26T08:00:00Z</published>
    <content type="html">&lt;b xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Fungipod protrusions on human immature dendritic cells.&lt;/b&gt;
&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Dendritic cells use the C-type lectin CD206 (Mannose Receptor) to recognize fungal cells.  &lt;a href="http://dx.doi.org/10.1371/journal.ppat.1000760"&gt;Neumann and Jacobson&lt;/a&gt; (doi:10.1371/journal.ppat.1000760) report the discovery of the fungipod, a novel protrusive structure triggered on dendritic cells after CD206 engagement by yeast.  Fungipods are long, conical motile structures with abundant F-actin, as shown in this projection image of a phalloidin-stained dendritic cell bearing several fungipods.  Both &lt;i&gt;S. cerevisiae&lt;/i&gt; and some pathogenic &lt;i&gt;Candida&lt;/i&gt; species induce fungipods. &lt;/p&gt;&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;&lt;i&gt;Image Credit: Aaron K. Neumann and Ken Jacobson, University of North Carolina, Chapel Hill&lt;/i&gt;&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/ALR76MR9nks" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fimage.ppat.v06.i02</feedburner:origLink></entry>
  <entry>
    <title>IL-1β Processing in Host Defense: Beyond the Inflammasomes</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/PVFyWrk7EOY/info%3Adoi%2F10.1371%2Fjournal.ppat.1000661" title="IL-1β Processing in Host Defense: Beyond the Inflammasomes" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000661&amp;representation=XML" title="(XML) IL-1β Processing in Host Defense: Beyond the Inflammasomes" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000661&amp;representation=PDF" title="(PDF) IL-1β Processing in Host Defense: Beyond the Inflammasomes" />
    <author>
      <name>Mihai G. Netea et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000661</id>
    <updated>2010-02-26T08:00:00Z</updated>
    <published>2010-02-26T08:00:00Z</published>
    <content type="html">&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Stimulation and release of proinflammatory cytokines is an essential step for the activation of an effective innate host defense, and subsequently for the modulation of adaptive immune responses. Interleukin-1β (IL-1β) and IL-18 are important proinflammatory cytokines that on the one hand activate monocytes, macropages, and neutrophils, and on the other hand induce Th1 and Th17 adaptive cellular responses. They are secreted as inactive precursors, and the processing of pro-IL-1β and pro-IL-18 depends on cleavage by proteases. One of the most important of these enzymes is caspase-1, which in turn is activated by several protein platforms called the inflammasomes. Inflammasome activation differs in various cell types, and knock-out mice defective in either caspase-1 or inflammasome components have an increased susceptibility to several types of infections. However, in other infections and in models of sterile inflammation, caspase-1 seems to be less important, and alternative mechanisms such as neutrophil-derived serine proteases or proteases released from microbial pathogens can process and activate IL-1β. In conclusion, IL-1β/IL-18 processing during infection is a complex process in which the inflammasomes are only one of several activation mechanisms.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/PVFyWrk7EOY" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000661</feedburner:origLink></entry>
  <entry>
    <title>HIV Controller CD4+ T Cells Respond to Minimal Amounts of Gag Antigen Due to High TCR Avidity</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/SGAES5jvmVg/info%3Adoi%2F10.1371%2Fjournal.ppat.1000780" title="HIV Controller CD4+ T Cells Respond to Minimal Amounts of Gag Antigen Due to High TCR Avidity" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000780&amp;representation=PDF" title="(PDF) HIV Controller CD4+ T Cells Respond to Minimal Amounts of Gag Antigen Due to High TCR Avidity" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000780&amp;representation=XML" title="(XML) HIV Controller CD4+ T Cells Respond to Minimal Amounts of Gag Antigen Due to High TCR Avidity" />
    <author>
      <name>Benoît Vingert et al.</name>
    </author>
    <contributor>
      <name>for the ANRS EP36 HIV Controllers Study Group</name>
    </contributor>
    <id>info:doi/10.1371/journal.ppat.1000780</id>
    <updated>2010-02-26T08:00:00Z</updated>
    <published>2010-02-26T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;HIV infection, if left untreated, leads to the progressive disruption of the immune system, the destruction of the CD4+ T cell population, and the occurrence of multiple opportunistic infections. However, a small fraction of HIV-infected individuals (less than 1%) avoid these deleterious effects by spontaneously controlling HIV replication to very low levels in the absence of antiretroviral therapy. Emerging evidence indicates that these rare patients, named HIV controllers, contain HIV through a very active T cell-mediated immune response. In this study, we found that memory CD4+ T cells from HIV controllers had the capacity to respond to minimal amounts of antigen derived from the viral protein Gag. This property was intrinsic to controller CD4+ T cells, and resulted from the expression of T cell receptors (TCRs) with high avidity for a particular Gag peptide. The presence of high avidity CD4+ T cells may explain how HIV controllers maintain the antiviral immune response in constant alert, even though the amount of virus inducing this response is minimal. Based on this study, we propose that future candidate vaccines against HIV should induce high avidity memory CD4+ T cells, to mimic the rapid and persistent antiviral response characteristic of HIV controllers.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/SGAES5jvmVg" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000780</feedburner:origLink></entry>
  <entry>
    <title>Genome-Wide mRNA Expression Correlates of Viral Control in CD4+ T-Cells from HIV-1-Infected Individuals</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/TIHQ6EPiBJQ/info%3Adoi%2F10.1371%2Fjournal.ppat.1000781" title="Genome-Wide mRNA Expression Correlates of Viral Control in CD4+ T-Cells from HIV-1-Infected Individuals" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000781&amp;representation=PDF" title="(PDF) Genome-Wide mRNA Expression Correlates of Viral Control in CD4+ T-Cells from HIV-1-Infected Individuals" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000781&amp;representation=XML" title="(XML) Genome-Wide mRNA Expression Correlates of Viral Control in CD4+ T-Cells from HIV-1-Infected Individuals" />
    <author>
      <name>Margalida Rotger et al.</name>
    </author>
    <contributor>
      <name>The Swiss HIV Cohort Study and the Center for HIV/AIDS Vaccine Immunology</name>
    </contributor>
    <id>info:doi/10.1371/journal.ppat.1000781</id>
    <updated>2010-02-26T08:00:00Z</updated>
    <published>2010-02-26T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;There has been recent progress in understanding the genetic factors that modulate susceptibility to HIV-1 infection. Genetic variation explains to a certain extent differences in disease progression among individuals. Less is known regarding the contribution of differences in gene expression to viral control. The present study evaluated, genome-wide, gene expression levels in CD4+ T cell, the main target of HIV-1. Thereafter, it searched for genetic variants that would modify gene expression. Specific expression profiles associated with high levels of viremia—in particular, the upregulation of genes of the antiviral defense. In contrast, no expression profile associated with effective viral control. Multiple genetic variants modulated gene expression in CD4+ T cells; however, none had a strong influence on viral control. This integrated genome-wide assessment suggests that viral replication drives gene expression rather than expression pointing to mechanisms of viral control.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/TIHQ6EPiBJQ" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000781</feedburner:origLink></entry>
  <entry>
    <title>Mycobacterium tuberculosis Peptides Presented by HLA-E Molecules Are Targets for Human CD8+ T-Cells with Cytotoxic as well as Regulatory Activity</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/Zo7XItb_-1Y/info%3Adoi%2F10.1371%2Fjournal.ppat.1000782" title="Mycobacterium tuberculosis Peptides Presented by HLA-E Molecules Are Targets for Human CD8+ T-Cells with Cytotoxic as well as Regulatory Activity" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000782&amp;representation=XML" title="(XML) Mycobacterium tuberculosis Peptides Presented by HLA-E Molecules Are Targets for Human CD8+ T-Cells with Cytotoxic as well as Regulatory Activity" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000782&amp;representation=PDF" title="(PDF) Mycobacterium tuberculosis Peptides Presented by HLA-E Molecules Are Targets for Human CD8+ T-Cells with Cytotoxic as well as Regulatory Activity" />
    <author>
      <name>Simone A. Joosten et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000782</id>
    <updated>2010-02-26T08:00:00Z</updated>
    <published>2010-02-26T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;&lt;i&gt;Mycobacterium tuberculosis&lt;/i&gt; (Mtb) has infected about one-third of the world population, resulting in fatal pulmonary tuberculosis (TB) in 1.5 million people annually. Vaccination against Mtb has decreased disease incidence in young children but does not prevent pulmonary TB in adults. The immune response against Mtb comprises multiple players, one of which is the CD8&lt;sup&gt;+&lt;/sup&gt; T-cell. CD8&lt;sup&gt;+&lt;/sup&gt; T-cells recognize infected cells because Mtb derived peptides are presented on HLA class I molecules. Here, we studied the non-classical HLA molecule HLA-E as presenter of Mtb antigens. The Mtb genome contained multiple sequences that can be presented by human HLA-E. These peptides were recognized by CD8&lt;sup&gt;+&lt;/sup&gt; T-cells from healthy individuals that were sensitized to Mtb, resulting in CD8&lt;sup&gt;+&lt;/sup&gt; T-cell proliferation. These T-cells lysed mycobacterium infected cells in a HLA-E restricted manner. Additionally, these T-cells also inhibited proliferation of other T-cells in their vicinity, a property of regulatory T-cells. The dual functionality of these T-cells makes them interesting players during infection, probably balancing their function depending on the environment. These findings contribute to our understanding of the immune response towards Mtb and will be helpful in designing new and improved vaccines against TB.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/Zo7XItb_-1Y" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000782</feedburner:origLink></entry>
  <entry>
    <title>Transit through the Flea Vector Induces a Pretransmission Innate Immunity Resistance Phenotype in Yersinia pestis</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/Rw_xxVfEFPA/info%3Adoi%2F10.1371%2Fjournal.ppat.1000783" title="Transit through the Flea Vector Induces a Pretransmission Innate Immunity Resistance Phenotype in Yersinia pestis" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000783&amp;representation=PDF" title="(PDF) Transit through the Flea Vector Induces a Pretransmission Innate Immunity Resistance Phenotype in Yersinia pestis" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000783&amp;representation=XML" title="(XML) Transit through the Flea Vector Induces a Pretransmission Innate Immunity Resistance Phenotype in Yersinia pestis" />
    <author>
      <name>Viveka Vadyvaloo et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000783</id>
    <updated>2010-02-26T08:00:00Z</updated>
    <published>2010-02-26T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Bubonic plague cycles depend on the ability of &lt;i&gt;Yersinia pestis&lt;/i&gt; to alternately infect two very different hosts—a mammal and a flea. Like any arthropod-borne pathogen, &lt;i&gt;Y. pestis&lt;/i&gt; must sense host-specific environmental cues and regulate gene expression accordingly to produce a transmissible infection in the flea after being taken up in a blood meal, and again when it exits the flea and enters the mammal. We examined the &lt;i&gt;Y. pestis&lt;/i&gt; phenotype at the point of transmission by &lt;i&gt;in vivo&lt;/i&gt; gene expression analyses, the first description of the transcriptome of an arthropod-borne bacterium in its vector. In addition to genes associated with physiological adaptation to the flea gut, several &lt;i&gt;Y. pestis&lt;/i&gt; virulence factors required for resistance to innate immunity and dissemination in the mammal were induced in the flea, suggesting that the arthropod life stage primes &lt;i&gt;Y. pestis&lt;/i&gt; for successful infection of the mammal.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/Rw_xxVfEFPA" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000783</feedburner:origLink></entry>
  <entry>
    <title>A Major Role for the Plasmodium falciparum ApiAP2 Protein PfSIP2 in Chromosome End Biology</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/XIgJkAUEo0M/info%3Adoi%2F10.1371%2Fjournal.ppat.1000784" title="A Major Role for the Plasmodium falciparum ApiAP2 Protein PfSIP2 in Chromosome End Biology" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000784&amp;representation=XML" title="(XML) A Major Role for the Plasmodium falciparum ApiAP2 Protein PfSIP2 in Chromosome End Biology" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000784&amp;representation=PDF" title="(PDF) A Major Role for the Plasmodium falciparum ApiAP2 Protein PfSIP2 in Chromosome End Biology" />
    <author>
      <name>Christian Flueck et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000784</id>
    <updated>2010-02-26T08:00:00Z</updated>
    <published>2010-02-26T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;&lt;i&gt;Plasmodium falciparum&lt;/i&gt;, like many other unicellular pathogens, uses antigenic variation of surface proteins as a prime mechanism for immune evasion. Subtelomeric gene families, including the major virulence family &lt;i&gt;var&lt;/i&gt;, encode these antigens, and recent studies highlighted the important contribution of the specific biology of chromosome ends in regulation of their expression. &lt;i&gt;P. falciparum&lt;/i&gt; chromosome ends are enriched in epigenetic marks of eukaryotic heterochromatin; however, it remains unknown which proteins and regulatory DNA motifs are involved in the recruitment and organization of heterochromatin, and how they contribute to the role of subtelomere biology in this important pathogen. Here, we present the experimental identification and genome-wide characterization of PfSIP2, a member of the ApiAP2 family of transcription factors that are specific to &lt;i&gt;Plasmodium&lt;/i&gt; and related apicomplexan parasites. PfSIP2 binds to a conserved recognition sequence exclusively in heterochromatic domains upstream of subtelomeric &lt;i&gt;var&lt;/i&gt; genes and within telomere-associated repeat elements. Our results suggest important roles for this protein in several aspects of chromosome end biology, including &lt;i&gt;var&lt;/i&gt; gene silencing. They are furthermore highly relevant for future efforts to dissect the specific biology of &lt;i&gt;P. falciparum&lt;/i&gt; chromosome ends, and for our understanding of the role of ApiAP2 factors in parasite biology.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/XIgJkAUEo0M" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000784</feedburner:origLink></entry>
  <entry>
    <title>Vaccinia Protein F12 Has Structural Similarity to Kinesin Light Chain and Contains a Motor Binding Motif Required for Virion Export</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/jPs3YXU3Ueo/info%3Adoi%2F10.1371%2Fjournal.ppat.1000785" title="Vaccinia Protein F12 Has Structural Similarity to Kinesin Light Chain and Contains a Motor Binding Motif Required for Virion Export" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000785&amp;representation=PDF" title="(PDF) Vaccinia Protein F12 Has Structural Similarity to Kinesin Light Chain and Contains a Motor Binding Motif Required for Virion Export" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000785&amp;representation=XML" title="(XML) Vaccinia Protein F12 Has Structural Similarity to Kinesin Light Chain and Contains a Motor Binding Motif Required for Virion Export" />
    <author>
      <name>Gareth W. Morgan et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000785</id>
    <updated>2010-02-26T08:00:00Z</updated>
    <published>2010-02-26T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Vaccinia virus (VACV), the vaccine used to eradicate smallpox, exploits the host cell motor kinesin-1 to export virus particles to the cell surface. We demonstrate that the VACV F12 protein has structural similarity with kinesin light chain (KLC) and facilitates viral transport using a kinesin binding sequence (KBS) that is conserved in several neuronal proteins. Dysfunction of some of these neuronal proteins can contribute to diseases, such as Alzheimer's. Mutation of the KBS in protein F12 showed it is essential for kinesin recruitment to virions and for virion transport to the cell surface. These findings enhance our understanding of how viruses hijack the host cell transport system, demonstrate conservation of a kinesin binding motif in cellular and viral proteins and identify targets for drug development.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/jPs3YXU3Ueo" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000785</feedburner:origLink></entry>
  <entry>
    <title>Efficacy of the New Neuraminidase Inhibitor CS-8958 against H5N1 Influenza Viruses</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/xF8GQLA2zjo/info%3Adoi%2F10.1371%2Fjournal.ppat.1000786" title="Efficacy of the New Neuraminidase Inhibitor CS-8958 against H5N1 Influenza Viruses" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000786&amp;representation=PDF" title="(PDF) Efficacy of the New Neuraminidase Inhibitor CS-8958 against H5N1 Influenza Viruses" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000786&amp;representation=XML" title="(XML) Efficacy of the New Neuraminidase Inhibitor CS-8958 against H5N1 Influenza Viruses" />
    <author>
      <name>Maki Kiso et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000786</id>
    <updated>2010-02-26T08:00:00Z</updated>
    <published>2010-02-26T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Since the first human outbreak in Hong Kong in 1997, highly pathogenic H5N1 avian influenza A viruses have posed a threat to public health. Because some isolates exhibit resistance to oseltamivir, a WHO-recommended neuraminidase (NA) inhibitor for the treatment of H5N1 influenza infection, alternative antivirals are urgently needed. Here, we assessed the efficacy of CS-8958, a prodrug of the novel neuraminidase inhibitor R-125489, against highly pathogenic H5N1 influenza viruses in a murine lethal infection model. We found that CS-8958 confers more potent and long-lasting protection to mice against H5N1 influenza viruses, including oseltamivir-resistant mutants, than does oseltamivir. Further, we demonstrate that CS-8958 has substantial efficacy as both a therapeutic and a prophylactic agent against H5N1 influenza viruses in mice. CS-8958 is, therefore, a promising candidate antiviral for the prevention and treatment of influenza patients infected with H5N1 or other subtype viruses.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/xF8GQLA2zjo" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000786</feedburner:origLink></entry>
  <entry>
    <title>Five Questions about Viruses and MicroRNAs</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/dBmCR3xqBOo/info%3Adoi%2F10.1371%2Fjournal.ppat.1000787" title="Five Questions about Viruses and MicroRNAs" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000787&amp;representation=XML" title="(XML) Five Questions about Viruses and MicroRNAs" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000787&amp;representation=PDF" title="(PDF) Five Questions about Viruses and MicroRNAs" />
    <author>
      <name>Bryan R. Cullen</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000787</id>
    <updated>2010-02-26T08:00:00Z</updated>
    <published>2010-02-26T08:00:00Z</published>
    <content type="html">&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/dBmCR3xqBOo" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000787</feedburner:origLink></entry>
  <entry>
    <title>Quantitative Comparison of HTLV-1 and HIV-1 Cell-to-Cell Infection with New Replication Dependent Vectors</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/kIwbfQqJHBE/info%3Adoi%2F10.1371%2Fjournal.ppat.1000788" title="Quantitative Comparison of HTLV-1 and HIV-1 Cell-to-Cell Infection with New Replication Dependent Vectors" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000788&amp;representation=PDF" title="(PDF) Quantitative Comparison of HTLV-1 and HIV-1 Cell-to-Cell Infection with New Replication Dependent Vectors" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000788&amp;representation=XML" title="(XML) Quantitative Comparison of HTLV-1 and HIV-1 Cell-to-Cell Infection with New Replication Dependent Vectors" />
    <author>
      <name>Dmitriy Mazurov et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000788</id>
    <updated>2010-02-26T08:00:00Z</updated>
    <published>2010-02-26T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Cell-free virus particles released from infected cells can be transmitted to target cells by diffusion or may be conveyed directly to target cells via specific intercellular contacts; the latter is referred to as cell-to-cell infection. Microscopic imaging has shown how viral proteins and virus particles move within and between cells, accumulating at sites of cell-cell contact. While we suspect that these images represent virus infection, it has been difficult to accurately quantify virus replication and provirus formation in most cell-to-cell infection experiments. Retroviral vectors that encode reporter proteins have been invaluable tools for analyzing retrovirus replication and restriction, but they have had limited utility in cell-to-cell infection studies due to high background noise resulting from reporter expression in the producer cells. We report the construction and characterization of retroviral vectors that express reporter protein exclusively in target cells and only after completing a full replication cycle. We have validated this approach and have begun to analyze cell and virus determinants for cell-to-cell infection with vectors for two human retroviruses that infect T cells. We show that the mechanism of transmission and ensuing virus replication depend on the particular virus, the effector and target cell types, and on the specific type of cell-cell interaction.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/kIwbfQqJHBE" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000788</feedburner:origLink></entry>
  <entry>
    <title>Differentiation, Distribution and γδ T Cell-Driven Regulation of IL-22-Producing T Cells in Tuberculosis</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/orFTccMI1Ug/info%3Adoi%2F10.1371%2Fjournal.ppat.1000789" title="Differentiation, Distribution and γδ T Cell-Driven Regulation of IL-22-Producing T Cells in Tuberculosis" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000789&amp;representation=PDF" title="(PDF) Differentiation, Distribution and γδ T Cell-Driven Regulation of IL-22-Producing T Cells in Tuberculosis" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000789&amp;representation=XML" title="(XML) Differentiation, Distribution and γδ T Cell-Driven Regulation of IL-22-Producing T Cells in Tuberculosis" />
    <author>
      <name>Shuyu Yao et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000789</id>
    <updated>2010-02-26T08:00:00Z</updated>
    <published>2010-02-26T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;TB remains one of the leading causes of morbidity and mortality among infectious diseases worldwide. Protective immunity against TB in humans remains poorly characterized, although the importance of CD4 T cells is well described in HIV-related TB. Similarly, little is known about the role of newly-defined T helper 17 (Th17) cells producing pro-inflammatory cytokine IL-17 or IL-22 during &lt;i&gt;M. tuberculosis&lt;/i&gt; infection of humans. Understanding immune response, kinetics, distribution and regulation of Th17 cells will help to elucidate immune function of these cells in TB, and to explore Th17-targeted immunotherapeutics. We therefore employed the nonhuman primate TB model to study Th17 cells and their interaction with Vγ2Vδ2 T cells, a major human γδ T-cell subset having regulatory potential. We demonstrated that &lt;i&gt;M. tuberculosis&lt;/i&gt; infection drove induction and distribution of IL-22-producing T cells in blood, airway, lung, lymph node and spleen. IL-22-producing T cells were most frequent in lungs, and involved in TB granuloma formation. We further showed that activation of Vγ2Vδ2 T cells could remarkably down-regulate IL-22-producing T cells in blood and tissue lymphocytes, and that such a down-regulation was mediated by an IFNγ-associated cytokine network. Our findings provide new information regarding kinetics, distribution and immune regulation of IL-22-producing T cells in TB.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/orFTccMI1Ug" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000789</feedburner:origLink></entry>
  <entry>
    <title>Caspase-1 Activation via Rho GTPases: A Common Theme in Mucosal Infections?</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/eVUyJnZlc5I/info%3Adoi%2F10.1371%2Fjournal.ppat.1000795" title="Caspase-1 Activation via Rho GTPases: A Common Theme in Mucosal Infections?" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000795&amp;representation=PDF" title="(PDF) Caspase-1 Activation via Rho GTPases: A Common Theme in Mucosal Infections?" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000795&amp;representation=XML" title="(XML) Caspase-1 Activation via Rho GTPases: A Common Theme in Mucosal Infections?" />
    <author>
      <name>Andreas J. Müller et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000795</id>
    <updated>2010-02-26T08:00:00Z</updated>
    <published>2010-02-26T08:00:00Z</published>
    <content type="html">&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/eVUyJnZlc5I" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000795</feedburner:origLink></entry>
  <entry>
    <title>Broadly Protective Monoclonal Antibodies against H3 Influenza Viruses following Sequential Immunization with Different Hemagglutinins</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/Z1nCd5GE_go/info%3Adoi%2F10.1371%2Fjournal.ppat.1000796" title="Broadly Protective Monoclonal Antibodies against H3 Influenza Viruses following Sequential Immunization with Different Hemagglutinins" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000796&amp;representation=PDF" title="(PDF) Broadly Protective Monoclonal Antibodies against H3 Influenza Viruses following Sequential Immunization with Different Hemagglutinins" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000796&amp;representation=XML" title="(XML) Broadly Protective Monoclonal Antibodies against H3 Influenza Viruses following Sequential Immunization with Different Hemagglutinins" />
    <author>
      <name>Taia T. Wang et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000796</id>
    <updated>2010-02-26T08:00:00Z</updated>
    <published>2010-02-26T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Influenza viruses remain a formidable public health threat. Because of a dramatic increase in drug resistant strains of influenza viruses and due to the semi-regular emergence of pandemic virus strains, the development of novel antibody-based therapies and influenza vaccine constructs is of great interest. Recently, monoclonal antibodies with broad neutralizing activity against an array of Group 1 influenza viruses (including H5 and H1 subtypes) were identified; studies using these antibodies have expanded our understanding of structural aspects of the viral hemagglutinin, the molecule mediating protective immunity to influenza viruses. We have identified the first broadly neutralizing antibodies against viruses in Group 2—specifically, they are active against H3 influenza viruses spanning 40 years. The antibodies react with the hemagglutinin and appear to bind in regions that are refractory to the structural variation required for viral escape from neutralization. The antibodies demonstrate therapeutic efficacy in mice against H3N2 virus infection and have potential for use in the treatment of human influenza disease. By mapping the binding region of one antibody, 12D1, we have identified a continuous region of the hemagglutinin that may act as an immunogen to elicit an immune response conferring broad protection against H3 viruses.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/Z1nCd5GE_go" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000796</feedburner:origLink></entry>
  <entry>
    <title>The Disulfide Bonds in Glycoprotein E2 of Hepatitis C Virus Reveal the Tertiary Organization of the Molecule</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/JwuFxCynJVs/info%3Adoi%2F10.1371%2Fjournal.ppat.1000762" title="The Disulfide Bonds in Glycoprotein E2 of Hepatitis C Virus Reveal the Tertiary Organization of the Molecule" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000762&amp;representation=XML" title="(XML) The Disulfide Bonds in Glycoprotein E2 of Hepatitis C Virus Reveal the Tertiary Organization of the Molecule" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000762&amp;representation=PDF" title="(PDF) The Disulfide Bonds in Glycoprotein E2 of Hepatitis C Virus Reveal the Tertiary Organization of the Molecule" />
    <author>
      <name>Thomas Krey et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000762</id>
    <updated>2010-02-19T08:00:00Z</updated>
    <published>2010-02-19T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Little is known about the structure of the envelope glycoproteins of the hepatitis C virus (HCV), in spite of their essential role in the viral cycle of this major human pathogen. Here, we determined the connectivity of the 9 disulfide bonds formed by the strictly conserved 18 cysteines of the ectodomain of HCV glycoprotein E2. We show that this information, together with important functional data available in the literature, impose important restrictions to the possible three-dimensional fold of the molecule. Indeed, these constraints allow the unambiguous threading of the predicted secondary structure elements along the polypeptide chain onto the template provided by the crystal structures of related flavi- and alphavirus class II fusion proteins. The resulting model of the tertiary organization of E2 shows the amino acid distribution among the characteristic class II domains, places the CD81 binding site at the interface of domains I and III, and highlights the location of a candidate fusion loop.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/JwuFxCynJVs" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000762</feedburner:origLink></entry>
  <entry>
    <title>IFN-α-Induced Upregulation of CCR5 Leads to Expanded HIV Tropism In Vivo</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/W_3ikGB8L0I/info%3Adoi%2F10.1371%2Fjournal.ppat.1000766" title="IFN-α-Induced Upregulation of CCR5 Leads to Expanded HIV Tropism In Vivo" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000766&amp;representation=PDF" title="(PDF) IFN-α-Induced Upregulation of CCR5 Leads to Expanded HIV Tropism In Vivo" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000766&amp;representation=XML" title="(XML) IFN-α-Induced Upregulation of CCR5 Leads to Expanded HIV Tropism In Vivo" />
    <author>
      <name>Cheryl A. Stoddart et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000766</id>
    <updated>2010-02-19T08:00:00Z</updated>
    <published>2010-02-19T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Human immunodeficiency virus (HIV), a lentivirus, is the causative agent of AIDS. Chronic immune activation and inflammation are major determinants of disease progression in primate lentivirus infections and are associated with the production of type I interferon. To investigate the impact of type I interferon on HIV infection, we studied the human thymus implants of SCID-hu Thy/Liv mice infected with HIV that uses either CXCR4 (X4 HIV) or CCR5 (R5 HIV) as a coreceptor. X4 HIV was observed to infect T-cell progenitors in the thymus and to disrupt T-cell production by that organ. R5 HIV, by contrast, first established a nondisruptive infection of thymic macrophages and then began to infect intrathymic T-cell progenitors. We report here that the tropism of R5 HIV is expanded and T-cell disruption enhanced by increased expression of CCR5 on these key T-cell progenitors. Such CCR5 induction was mediated by interferon-α (IFN-α) in both thymic organ cultures and in SCID-hu mice. Moreover, antibody neutralization of IFN-α in R5 HIV-infected SCID-hu mice inhibited both CCR5 upregulation and infection of the T-cell progenitors. These observations suggest a mechanism by which IFN-α may paradoxically expand the tropism of R5 HIV and accelerate disease progression.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/W_3ikGB8L0I" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000766</feedburner:origLink></entry>
  <entry>
    <title>Long-Lived Antibody and B Cell Memory Responses to the Human Malaria Parasites, Plasmodium falciparum and Plasmodium vivax</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/4ieNLG2_MUw/info%3Adoi%2F10.1371%2Fjournal.ppat.1000770" title="Long-Lived Antibody and B Cell Memory Responses to the Human Malaria Parasites, Plasmodium falciparum and Plasmodium vivax" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000770&amp;representation=XML" title="(XML) Long-Lived Antibody and B Cell Memory Responses to the Human Malaria Parasites, Plasmodium falciparum and Plasmodium vivax" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000770&amp;representation=PDF" title="(PDF) Long-Lived Antibody and B Cell Memory Responses to the Human Malaria Parasites, Plasmodium falciparum and Plasmodium vivax" />
    <author>
      <name>Jiraprapa Wipasa et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000770</id>
    <updated>2010-02-19T08:00:00Z</updated>
    <published>2010-02-19T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;It is widely perceived that immunity to malaria is short-lived, rendering people susceptible to repeated malaria infections. However, there have been very few studies on “memory” responses, how the human immune system recognizes previously encountered malaria parasites. In particular, very little is known about the durability of malaria-specific B cells and antibodies. The aim of this study was to investigate the induction and maintenance of B cell memory responses to malaria parasites in a region of Thailand where people become infected with malaria, but where the levels of malaria transmission are so low that repeated infection is uncommon. From hospital records we were able to identify people who either had been infected with malaria over the past 6 years and/or had never been infected. Blood samples were collected on four separate occasions over a period of one year and analysed by microscopy and PCR for presence of malaria parasites and by ELISA and ELISPOT for anti malarial antibodies and malaria-specific memory B cells. We found that, in a significant proportion of individuals, malaria infection results in the generation of antibodies and the establishment of populations of memory B cells against malaria parasites, which were very stably maintained over time despite the lack of any evidence of malaria reinfection. Contrary to the widely held idea that memory to malaria is suboptimally induced, our data demonstrate that B cell responses to malaria can be maintained for many years after a malaria infection and indicate that there is no inherent reason why malaria vaccines should not also induce long-lasting protection against malaria.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/4ieNLG2_MUw" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000770</feedburner:origLink></entry>
  <entry>
    <title>Arterivirus Nsp1 Modulates the Accumulation of Minus-Strand Templates to Control the Relative Abundance of Viral mRNAs</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/8t6gEufI8sU/info%3Adoi%2F10.1371%2Fjournal.ppat.1000772" title="Arterivirus Nsp1 Modulates the Accumulation of Minus-Strand Templates to Control the Relative Abundance of Viral mRNAs" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000772&amp;representation=PDF" title="(PDF) Arterivirus Nsp1 Modulates the Accumulation of Minus-Strand Templates to Control the Relative Abundance of Viral mRNAs" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000772&amp;representation=XML" title="(XML) Arterivirus Nsp1 Modulates the Accumulation of Minus-Strand Templates to Control the Relative Abundance of Viral mRNAs" />
    <author>
      <name>Danny D. Nedialkova et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000772</id>
    <updated>2010-02-19T08:00:00Z</updated>
    <published>2010-02-19T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Plus-strand RNA viruses, a major group of plant and animal pathogens, employ a variety of gene expression strategies. In some groups, the genome is translated into a single polyprotein precursor comprising all viral proteins, while the expression of genomes containing multiple open reading frames commonly depends on the production of additional, subgenomic mRNAs. These serve to translate the open reading frames that are inaccessible to host cell ribosomes engaged in genome translation. Arteriviruses and coronaviruses secure the expression of their structural protein genes by generating an extensive nested set of subgenomic mRNAs, which are copied from a set of complementary minus-strand templates. The production of these subgenome-length minus strands involves a unique mechanism of discontinuous RNA synthesis that essentially competes with the production of the full-length minus strand, the template for genome replication. We describe here that arterivirus non-structural protein 1 (nsp1) modulates the accumulation of minus-strand RNAs to control the relative abundance of both genome-length and subgenomic mRNAs, thereby ensuring efficient production of new virus particles. We found that specific nsp1 mutants with imbalanced mRNA levels and low virus production rapidly acquire additional nsp1 mutations that rescue these defects. Thus, a single arterivirus protein plays a decisive role in the integral control of replication, sg mRNA synthesis, and virus production.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/8t6gEufI8sU" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000772</feedburner:origLink></entry>
  <entry>
    <title>Anaplasma phagocytophilum Ats-1 Is Imported into Host Cell Mitochondria and Interferes with Apoptosis Induction</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/4SG8yeRMhOc/info%3Adoi%2F10.1371%2Fjournal.ppat.1000774" title="Anaplasma phagocytophilum Ats-1 Is Imported into Host Cell Mitochondria and Interferes with Apoptosis Induction" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000774&amp;representation=PDF" title="(PDF) Anaplasma phagocytophilum Ats-1 Is Imported into Host Cell Mitochondria and Interferes with Apoptosis Induction" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000774&amp;representation=XML" title="(XML) Anaplasma phagocytophilum Ats-1 Is Imported into Host Cell Mitochondria and Interferes with Apoptosis Induction" />
    <author>
      <name>Hua Niu et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000774</id>
    <updated>2010-02-19T08:00:00Z</updated>
    <published>2010-02-19T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;&lt;i&gt;Anaplasma phagocytophilum&lt;/i&gt; is the pathogen that causes human granulocytic anaplasmosis, an emerging infectious disease. As an obligate intracellular organism, this bacterium cannot reproduce outside of eukaryotic cells due to the loss of many genes that are present in free-living bacteria. Paradoxically, it specifically infects short-lived white blood cells that play critical roles in anti-microbial defense, by subverting a number of host innate immune responses including programmed cell death (apoptosis). &lt;i&gt;A. phagocytophilum&lt;/i&gt; factors that are involved in this process are largely unknown. In this study, we first searched &lt;i&gt;A. phagocytophilum&lt;/i&gt; proteins that are secreted by its specialized secretion system into eukaryotic cells. We found a protein of unknown function, here named Ats-1, which is abundantly produced by &lt;i&gt;A. phagocytophilum&lt;/i&gt; and traverses five membranes to enter the mitochondria of human cells. Our further study showed that Ats-1 reduces the sensitivity of mitochondria to respond to apoptosis-inducing factors, leading to the inhibition of host cell apoptosis. Thus, present findings identified a bacterial protein that allows infected white blood cells to live longer to support bacterial growth. The absence of similarity of the sequence or the mode of action to any other known cell death suppressor suggests that Ats-1 defines a previously undescribed class of anti-apoptotic protein. This protein and the mechanism thereof may provide insight regarding a new therapeutic target for treatment of human granulocytic anaplasmosis.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/4SG8yeRMhOc" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000774</feedburner:origLink></entry>
  <entry>
    <title>A New Nuclear Function of the Entamoeba histolytica Glycolytic Enzyme Enolase: The Metabolic Regulation of Cytosine-5 Methyltransferase 2 (Dnmt2) Activity</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/AucKMLJRa4o/info%3Adoi%2F10.1371%2Fjournal.ppat.1000775" title="A New Nuclear Function of the Entamoeba histolytica Glycolytic Enzyme Enolase: The Metabolic Regulation of Cytosine-5 Methyltransferase 2 (Dnmt2) Activity" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000775&amp;representation=PDF" title="(PDF) A New Nuclear Function of the Entamoeba histolytica Glycolytic Enzyme Enolase: The Metabolic Regulation of Cytosine-5 Methyltransferase 2 (Dnmt2) Activity" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000775&amp;representation=XML" title="(XML) A New Nuclear Function of the Entamoeba histolytica Glycolytic Enzyme Enolase: The Metabolic Regulation of Cytosine-5 Methyltransferase 2 (Dnmt2) Activity" />
    <author>
      <name>Ayala Tovy et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000775</id>
    <updated>2010-02-19T08:00:00Z</updated>
    <published>2010-02-19T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Epigenetics refers to heritable changes in gene function that occur without alterations in the DNA sequence. The best characterized epigenetic modification is DNA methylation. In mammals, DNA methylation is associated with gene silencing and transposon control. We have previously established the presence of methyl cytosine in the genome of &lt;i&gt;Entamoeba histolytica&lt;/i&gt;, an important unicellular human pathogen. Ehmeth, an enzyme that belongs to the DNA methyltransferase 2 (Dnmt2) family, catalyzes DNA methylation in the parasite. Recent evidence in support of the notion that human Dnmt2 is a tRNA&lt;sup&gt;Asp&lt;/sup&gt; methyltransferase fuels the debate about the real function of the Dnmt2 family. Our results show that Ehmeth also catalyzes tRNA&lt;sup&gt;Asp&lt;/sup&gt; methylation and indicates a dual function for this protein. In this study, we have also identified that enolase, a glycolytic enzyme, interacts with Ehmeth, and modulates its activity under conditions of glucose starvation. These data add to the emerging evidence that glycolytic enzymes have multifunctional roles, and emphasize the importance of energetic metabolism in the control of the epigenetic enzymatic machinery.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/AucKMLJRa4o" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000775</feedburner:origLink></entry>
  <entry>
    <title>Interaction of Cryptococcus neoformans Rim101 and Protein Kinase A Regulates Capsule</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/lN-jtGe3i8U/info%3Adoi%2F10.1371%2Fjournal.ppat.1000776" title="Interaction of Cryptococcus neoformans Rim101 and Protein Kinase A Regulates Capsule" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000776&amp;representation=XML" title="(XML) Interaction of Cryptococcus neoformans Rim101 and Protein Kinase A Regulates Capsule" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000776&amp;representation=PDF" title="(PDF) Interaction of Cryptococcus neoformans Rim101 and Protein Kinase A Regulates Capsule" />
    <author>
      <name>Teresa R. O'Meara et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000776</id>
    <updated>2010-02-19T08:00:00Z</updated>
    <published>2010-02-19T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;&lt;i&gt;Cryptococcus neoformans&lt;/i&gt; is an environmental fungus and an opportunistic human pathogen. Survival of this fungus within a human host depends on its ability to sense the host environment and respond with protective cellular changes. It is known that the cAMP/PKA signal transduction cascade is important for sensing host-specific environments and regulating the cellular adaptations, such as capsule and increased iron uptake, that are necessary for growth inside the infected host. Here we document that, unlike what has been described in other fungal species, a &lt;i&gt;C. neoformans&lt;/i&gt; Rim101 homologue is directly regulated by PKA. The Rim101 signaling pathway is also involved in capsule regulation and virulence. Our study demonstrates that Rim101 integrates two conserved signal transduction cascades, and it is important in regulating microbial pathogenesis.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/lN-jtGe3i8U" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000776</feedburner:origLink></entry>
  <entry>
    <title>Optineurin Negatively Regulates the Induction of IFNβ in Response to RNA Virus Infection</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/gEUN4hrllys/info%3Adoi%2F10.1371%2Fjournal.ppat.1000778" title="Optineurin Negatively Regulates the Induction of IFNβ in Response to RNA Virus Infection" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000778&amp;representation=XML" title="(XML) Optineurin Negatively Regulates the Induction of IFNβ in Response to RNA Virus Infection" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000778&amp;representation=PDF" title="(PDF) Optineurin Negatively Regulates the Induction of IFNβ in Response to RNA Virus Infection" />
    <author>
      <name>Jamel Mankouri et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000778</id>
    <updated>2010-02-19T08:00:00Z</updated>
    <published>2010-02-19T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;Viral infection stimulates the innate immune response to produce various cytokines and chemokines to induce an anti-viral state within the host. The best studied of these are the type I interferons (IFNα/β), which are essential for an effective anti-viral response. Our understanding of how IFNβ is regulated is not well understood. This study demonstrates that the Nemo-related protein optineurin helps to regulate the levels of IFNβ in response to virus infection. We expressed optineurin in cells and found that the cells failed to express IFNβ when infected with various RNA viruses. Using biochemical experiments we showed that optineurin interacts with the protein kinase TBK1 and the ubiquitin ligase TRAF3. Furthermore, a mutation in optineurin that prevents the interaction with the small protein modifier ubiquitin (D474N) ablated the negative regulatory function of optineurin. Our findings provide a first example of a role for optineurin in anti-viral signalling and aid in our understanding of the negative regulation of IFNβ.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/gEUN4hrllys" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000778</feedburner:origLink></entry>
  <entry>
    <title>Highly Differentiated, Resting Gn-Specific Memory CD8+ T Cells Persist Years after Infection by Andes Hantavirus</title>
    <link rel="alternate" href="http://feeds.plos.org/~r/plospathogens/NewArticles/~3/pA2Pnw5xmCw/info%3Adoi%2F10.1371%2Fjournal.ppat.1000779" title="Highly Differentiated, Resting Gn-Specific Memory CD8+ T Cells Persist Years after Infection by Andes Hantavirus" />
    <link rel="related" type="application/pdf" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000779&amp;representation=PDF" title="(PDF) Highly Differentiated, Resting Gn-Specific Memory CD8+ T Cells Persist Years after Infection by Andes Hantavirus" />
    <link rel="related" type="text/xml" href="http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info:doi/10.1371/journal.ppat.1000779&amp;representation=XML" title="(XML) Highly Differentiated, Resting Gn-Specific Memory CD8+ T Cells Persist Years after Infection by Andes Hantavirus" />
    <author>
      <name>Tobias Manigold et al.</name>
    </author>
    <id>info:doi/10.1371/journal.ppat.1000779</id>
    <updated>2010-02-19T08:00:00Z</updated>
    <published>2010-02-19T08:00:00Z</published>
    <content type="html">Author Summary

&lt;p xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:fn="http://www.w3.org/2005/xpath-functions" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:util="http://dtd.nlm.nih.gov/xsl/util" xmlns:fo="http://www.w3.org/1999/XSL/Format" xmlns:mml="http://www.w3.org/1998/Math/MathML"&gt;In man, hantavirus cardiopulmonary syndrome (HCPS) caused by Andes Virus (ANDV) is endemic in the Southern cone of Chile and Argentina but cases of HCPS are being increasingly reported all over South America since 1995. HCPS is characterized by fulminant pulmonary edema which progresses to shock and death in about 36% of patients with HCPS. Nevertheless, to date, neither antiviral treatments nor vaccines inducing neutralizing antibodies (NAb) have proven effective against HCPS-causing hantaviruses. We set out for the first study on human cellular immunity towards ANDV in 78 convalescent survivors of ANDV infection. We found that Gn-specific responses were predominant as compared to N- and Gc-specific responses, even up to 13 years after the infection. Surprisingly, most of the Gn-specific responses were restricted to two neighboring epitopes within the Gn carboxyterminus. Interestingly, among HLA-B*3501&lt;sup&gt;+&lt;/sup&gt; patients, Gn&lt;sub&gt;465−473&lt;/sub&gt;-specific CD8&lt;sup&gt;+&lt;/sup&gt; T-cells showed highly differentiated but resting phenotype and functions. It remains to be seen in future studies whether the immunodominace of Gn-specific T-cells is crucial for protective immunity. Most intriguingly, titers of neutralizing antibodies increased in 10/17 individuals months to years after the acute infection and independently of whether they were residents of endemic areas or not. Thus, our data suggest viral persistence or latency in part of ANDV-convalescent patients. However, it remains a major task for future studies to proof the concept of latent/persistent human ANDV infection by the determination of viral antigen in convalescent patients.&lt;/p&gt;&lt;img src="http://feeds.feedburner.com/~r/plospathogens/NewArticles/~4/pA2Pnw5xmCw" height="1" width="1"/&gt;</content>
  <feedburner:origLink>http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000779</feedburner:origLink></entry>
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