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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Severe Acute Respiratory Syndrome Coronavirus Protein 6 Accelerates Murine Coronavirus Infections<xref ref-type="fn" rid="fn1">▿</xref>
</title>
<author><name sortKey="Tangudu, Chandra" sort="Tangudu, Chandra" uniqKey="Tangudu C" first="Chandra" last="Tangudu">Chandra Tangudu</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Olivares, Heidi" sort="Olivares, Heidi" uniqKey="Olivares H" first="Heidi" last="Olivares">Heidi Olivares</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Netland, Jason" sort="Netland, Jason" uniqKey="Netland J" first="Jason" last="Netland">Jason Netland</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Gallagher, Thomas" sort="Gallagher, Thomas" uniqKey="Gallagher T" first="Thomas" last="Gallagher">Thomas Gallagher</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">17108045</idno>
<idno type="pmc">1797517</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1797517</idno>
<idno type="RBID">PMC:1797517</idno>
<idno type="doi">10.1128/JVI.01515-06</idno>
<date when="2006">2006</date>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Severe Acute Respiratory Syndrome Coronavirus Protein 6 Accelerates Murine Coronavirus Infections<xref ref-type="fn" rid="fn1">▿</xref>
</title>
<author><name sortKey="Tangudu, Chandra" sort="Tangudu, Chandra" uniqKey="Tangudu C" first="Chandra" last="Tangudu">Chandra Tangudu</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Olivares, Heidi" sort="Olivares, Heidi" uniqKey="Olivares H" first="Heidi" last="Olivares">Heidi Olivares</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Netland, Jason" sort="Netland, Jason" uniqKey="Netland J" first="Jason" last="Netland">Jason Netland</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Gallagher, Thomas" sort="Gallagher, Thomas" uniqKey="Gallagher T" first="Thomas" last="Gallagher">Thomas Gallagher</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Journal of Virology</title>
<idno type="ISSN">0022-538X</idno>
<idno type="eISSN">1098-5514</idno>
<imprint><date when="2006">2006</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
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</teiHeader>
<front><div type="abstract" xml:lang="en"><p>One or more of the unique 3′-proximal open reading frames (ORFs) of the severe acute respiratory syndrome (SARS) coronavirus may encode determinants of virus virulence. A prime candidate is ORF6, which encodes a 63-amino-acid membrane-associated peptide that can dramatically increase the lethality of an otherwise attenuated JHM strain of murine coronavirus (L. Pewe, H. Zhou, J. Netland, C. Tangudu, H. Olivares, L. Shi, D. Look, T. Gallagher, and S. Perlman, J. Virol. 79:11335-11342, 2005). To discern virulence mechanisms, we compared the in vitro growth properties of rJ.6, a recombinant JHM expressing the SARS peptide, with isogenic rJ.6-KO, which has an inactive ORF containing a mutated initiation codon and a termination codon at internal position 27. The rJ.6 infections proceeded rapidly, secreting progeny about 1.5 h earlier than rJ.6-KO infections did. The rJ.6 infections were also set apart by early viral protein accumulation and by robust expansion via syncytia, a characteristic feature of JHM virus dissemination. We found no evidence for protein 6 operating at the virus entry or assembly stage, as virions from either infection were indistinguishable. Rather, protein 6 appeared to operate by fostering viral RNA and protein synthesis, as RNA quantifications by reverse transcription-quantitative PCR revealed viral RNA levels in the rJ.6 cultures that were five to eight times higher than those lacking protein 6. Furthermore, protein 6 coimmunoprecipitated with viral RNAs and colocalized on cytoplasmic vesicles with replicating viral RNAs. The SARS coronavirus encodes a novel membrane protein 6 that can accelerate replication of a related mouse virus, a property that may explain its ability to increase in vivo virus virulence.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Virol</journal-id>
<journal-id journal-id-type="publisher-id">jvi</journal-id>
<journal-title>Journal of Virology</journal-title>
<issn pub-type="ppub">0022-538X</issn>
<issn pub-type="epub">1098-5514</issn>
<publisher><publisher-name>American Society for Microbiology</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">17108045</article-id>
<article-id pub-id-type="pmc">1797517</article-id>
<article-id pub-id-type="publisher-id">1515-06</article-id>
<article-id pub-id-type="doi">10.1128/JVI.01515-06</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Virus-Cell Interactions</subject>
</subj-group>
</article-categories>
<title-group><article-title>Severe Acute Respiratory Syndrome Coronavirus Protein 6 Accelerates Murine Coronavirus Infections<xref ref-type="fn" rid="fn1">▿</xref>
</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Tangudu</surname>
<given-names>Chandra</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Olivares</surname>
<given-names>Heidi</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Netland</surname>
<given-names>Jason</given-names>
</name>
<xref ref-type="aff" rid="aff1">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Perlman</surname>
<given-names>Stanley</given-names>
</name>
<xref ref-type="aff" rid="aff1">2</xref>
<xref ref-type="aff" rid="aff1">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gallagher</surname>
<given-names>Thomas</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="corresp" rid="cor1">*</xref>
</contrib>
</contrib-group>
<aff id="aff1">Department of Microbiology and Immunology, Loyola University Medical Center, Maywood, Illinois,<label>1</label>
Interdisciplinary Program in Immunology,<label>2</label>
Department of Microbiology, University of Iowa, Iowa City, Iowa<label>3</label>
</aff>
<author-notes><fn id="cor1"><label>*</label>
<p>Corresponding author. Mailing address: Department of Microbiology and Immunology, Loyola University Medical Center, 2160 South First Avenue, Maywood, IL 60153. Phone: (708) 216-4850. Fax: (708) 216-9574. E-mail: <email>tgallag@lumc.edu</email>
.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub"><month>2</month>
<year>2007</year>
</pub-date>
<pub-date pub-type="epub"><day>15</day>
<month>11</month>
<year>2006</year>
</pub-date>
<volume>81</volume>
<issue>3</issue>
<fpage>1220</fpage>
<lpage>1229</lpage>
<history><date date-type="received"><day>15</day>
<month>7</month>
<year>2006</year>
</date>
<date date-type="accepted"><day>2</day>
<month>11</month>
<year>2006</year>
</date>
</history>
<copyright-statement>Copyright © 2007, American Society for Microbiology</copyright-statement>
<copyright-year>2007</copyright-year>
<self-uri xlink:title="pdf" xlink:href="zjv00307001220.pdf"></self-uri>
<abstract><p>One or more of the unique 3′-proximal open reading frames (ORFs) of the severe acute respiratory syndrome (SARS) coronavirus may encode determinants of virus virulence. A prime candidate is ORF6, which encodes a 63-amino-acid membrane-associated peptide that can dramatically increase the lethality of an otherwise attenuated JHM strain of murine coronavirus (L. Pewe, H. Zhou, J. Netland, C. Tangudu, H. Olivares, L. Shi, D. Look, T. Gallagher, and S. Perlman, J. Virol. 79:11335-11342, 2005). To discern virulence mechanisms, we compared the in vitro growth properties of rJ.6, a recombinant JHM expressing the SARS peptide, with isogenic rJ.6-KO, which has an inactive ORF containing a mutated initiation codon and a termination codon at internal position 27. The rJ.6 infections proceeded rapidly, secreting progeny about 1.5 h earlier than rJ.6-KO infections did. The rJ.6 infections were also set apart by early viral protein accumulation and by robust expansion via syncytia, a characteristic feature of JHM virus dissemination. We found no evidence for protein 6 operating at the virus entry or assembly stage, as virions from either infection were indistinguishable. Rather, protein 6 appeared to operate by fostering viral RNA and protein synthesis, as RNA quantifications by reverse transcription-quantitative PCR revealed viral RNA levels in the rJ.6 cultures that were five to eight times higher than those lacking protein 6. Furthermore, protein 6 coimmunoprecipitated with viral RNAs and colocalized on cytoplasmic vesicles with replicating viral RNAs. The SARS coronavirus encodes a novel membrane protein 6 that can accelerate replication of a related mouse virus, a property that may explain its ability to increase in vivo virus virulence.</p>
</abstract>
</article-meta>
</front>
</pmc>
</record>
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