Severe acute respiratory syndrome coronavirus protein 6 accelerates murine coronavirus infections
Identifieur interne : 003B27 ( Main/Exploration ); précédent : 003B26; suivant : 003B28Severe acute respiratory syndrome coronavirus protein 6 accelerates murine coronavirus infections
Auteurs : Chandra Tangudu [États-Unis] ; Heidi Olivares [États-Unis] ; Jason Netland [États-Unis] ; Stanley Perlman [États-Unis] ; Thomas Gallagher [États-Unis]Source :
- Journal of virology [ 0022-538X ] ; 2007.
Descripteurs français
- Pascal (Inist)
English descriptors
Abstract
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.
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coronavirus protein 6 accelerates murine coronavirus infections</title><author><name sortKey="Tangudu, Chandra" sort="Tangudu, Chandra" uniqKey="Tangudu C" first="Chandra" last="Tangudu">Chandra Tangudu</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Microbiology and Immunology, Loyola University Medical Center</s1><s2>Maywood, Illinois</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Olivares, Heidi" sort="Olivares, Heidi" uniqKey="Olivares H" first="Heidi" last="Olivares">Heidi Olivares</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Microbiology and Immunology, Loyola University Medical Center</s1><s2>Maywood, Illinois</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Netland, Jason" sort="Netland, Jason" uniqKey="Netland J" first="Jason" last="Netland">Jason Netland</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Interdisciplinary Program in Immunology, University of Iowa</s1><s2>Iowa City, Iowa</s2><s3>USA</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation></author><author><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Interdisciplinary Program in Immunology, University of Iowa</s1><s2>Iowa City, Iowa</s2><s3>USA</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Department of Microbiology, University of Iowa</s1><s2>Iowa City, Iowa</s2><s3>USA</s3><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation></author><author><name sortKey="Gallagher, Thomas" sort="Gallagher, Thomas" uniqKey="Gallagher T" first="Thomas" last="Gallagher">Thomas Gallagher</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Microbiology and Immunology, Loyola University Medical Center</s1><s2>Maywood, Illinois</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Illinois</region></placeName></affiliation></author></analytic><series><title level="j" type="main">Journal of virology</title><title level="j" type="abbreviated">J. virol.</title><idno type="ISSN">0022-538X</idno><imprint><date when="2007">2007</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Journal of virology</title><title level="j" type="abbreviated">J. virol.</title><idno type="ISSN">0022-538X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Coronavirus</term><term>Murine hepatitis virus</term><term>Protein</term><term>Severe acute respiratory syndrome</term><term>Virology</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Coronavirus</term><term>Virus hépatite murine</term><term>Protéine</term><term>Virologie</term><term>Syndrome respiratoire aigu sévère</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Illinois</li><li>Iowa</li></region><settlement><li>Iowa City</li></settlement><orgName><li>Université de l'Iowa</li></orgName></list><tree><country name="États-Unis"><region name="Illinois"><name sortKey="Tangudu, Chandra" sort="Tangudu, Chandra" uniqKey="Tangudu C" first="Chandra" last="Tangudu">Chandra Tangudu</name></region><name sortKey="Gallagher, Thomas" sort="Gallagher, Thomas" uniqKey="Gallagher T" first="Thomas" last="Gallagher">Thomas Gallagher</name><name sortKey="Netland, Jason" sort="Netland, Jason" uniqKey="Netland J" first="Jason" last="Netland">Jason Netland</name><name sortKey="Olivares, Heidi" sort="Olivares, Heidi" uniqKey="Olivares H" first="Heidi" last="Olivares">Heidi Olivares</name><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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