Genetic Determinants of Mouse Hepatitis Virus Strain 1 Pneumovirulence
Identifieur interne : 002938 ( Main/Exploration ); précédent : 002937; suivant : 002939Genetic Determinants of Mouse Hepatitis Virus Strain 1 Pneumovirulence
Auteurs : Julian L. Leibowitz [États-Unis] ; Rajiv Srinivasa [États-Unis] ; Shawn T. Williamson [États-Unis] ; MING MING CHUA [États-Unis] ; MINGFENG LIU [Canada] ; SAMANTHA WU [Canada] ; HYOJEUNG KANG [États-Unis] ; Xue-Zhong Ma [Canada] ; JIANHUA ZHANG [Canada] ; Itay Shalev [Canada] ; Robert Smith [Canada] ; Melville J. Phillips [Canada] ; Gary A. Levy [Canada] ; Susan R. Weiss [États-Unis]Source :
- Journal of virology [ 0022-538X ] ; 2010.
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English descriptors
Abstract
We report here investigation into the genetic basis of mouse hepatitis virus strain 1 (MHV-1) pneumovirulence. Sequencing of the 3' one-third of the MHV-1 genome demonstrated that the genetic organization of MHV-1 was similar to that of other strains of MHV. The hemagglutinin esterase (HE) protein was truncated, and reverse transcription-PCR (RT-PCR) studies confirmed previous work that suggested that the MHV-1 HE is a pseudogene. Targeted recombination was used to select chimeric viruses containing either the MHV-1 S gene or genes encoding all of the MHV-1 structural proteins, on an MHV-A59 background. Challenge studies in mice demonstrated that expression of the MHV-1 S gene within the MHV-A59 background (rA59/SMHV-1) increased the pneumovirulence of MHV-A59, and mice infected with this recombinant virus developed pulmonary lesions that were similar to those observed with MHV-1, although rA59/SMHV-1 was significantly less virulent. Chimeras containing all of the MHV-1 structural genes on an MHV-A59 background were able to reproduce the severe acute respiratory syndrome (SARS)-like pathology observed with MHV-1 and reproducibly increased pneumovirulence relative to rA59/SMHV-1 but were still much less virulent than MHV-1. These data suggest that important determinants of pneumopathogenicity are contained within the 3' one-third of the MHV-1 genome, but additional important virulence factors must be encoded in the genome upstream of the S gene. The severity of the pulmonary lesions observed correlates better with elevated levels of inflammatory cytokines than with viral replication in the lungs, suggesting that pulmonary disease has an important immunological component.
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">Genetic Determinants of Mouse Hepatitis Virus Strain 1 Pneumovirulence</title><author><name sortKey="Leibowitz, Julian L" sort="Leibowitz, Julian L" uniqKey="Leibowitz J" first="Julian L." last="Leibowitz">Julian L. Leibowitz</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Microbial and Molecular Pathogenesis, Texas A&M University System-HSC, College of Medicine</s1><s2>College Station, Texas 77843-1114</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>College Station, Texas 77843-1114</wicri:noRegion></affiliation></author><author><name sortKey="Srinivasa, Rajiv" sort="Srinivasa, Rajiv" uniqKey="Srinivasa R" first="Rajiv" last="Srinivasa">Rajiv Srinivasa</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Microbial and Molecular Pathogenesis, Texas A&M University System-HSC, College of Medicine</s1><s2>College Station, Texas 77843-1114</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>College Station, Texas 77843-1114</wicri:noRegion></affiliation></author><author><name sortKey="Williamson, Shawn T" sort="Williamson, Shawn T" uniqKey="Williamson S" first="Shawn T." last="Williamson">Shawn T. Williamson</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Microbial and Molecular Pathogenesis, Texas A&M University System-HSC, College of Medicine</s1><s2>College Station, Texas 77843-1114</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>College Station, Texas 77843-1114</wicri:noRegion></affiliation></author><author><name sortKey="Ming Ming Chua" sort="Ming Ming Chua" uniqKey="Ming Ming Chua" last="Ming Ming Chua">MING MING CHUA</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Microbiology, University of Pennsylvania School of Medicine</s1><s2>Philadelphia, Pennsylvania 19104-6076</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Philadelphia, Pennsylvania 19104-6076</wicri:noRegion></affiliation></author><author><name sortKey="Mingfeng Liu" sort="Mingfeng Liu" uniqKey="Mingfeng Liu" last="Mingfeng Liu">MINGFENG LIU</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>University of Toronto Transplantation Institute</s1><s2>Toronto, Ontario, M5G 2N2</s2><s3>CAN</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>University of Toronto Transplantation Institute</wicri:noRegion></affiliation></author><author><name sortKey="Samantha Wu" sort="Samantha Wu" uniqKey="Samantha Wu" last="Samantha Wu">SAMANTHA WU</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>University of Toronto Transplantation Institute</s1><s2>Toronto, Ontario, M5G 2N2</s2><s3>CAN</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>University of Toronto Transplantation Institute</wicri:noRegion></affiliation></author><author><name sortKey="Hyojeung Kang" sort="Hyojeung Kang" uniqKey="Hyojeung Kang" last="Hyojeung Kang">HYOJEUNG KANG</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Microbial and Molecular Pathogenesis, Texas A&M University System-HSC, College of Medicine</s1><s2>College Station, Texas 77843-1114</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>College Station, Texas 77843-1114</wicri:noRegion></affiliation></author><author><name sortKey="Ma, Xue Zhong" sort="Ma, Xue Zhong" uniqKey="Ma X" first="Xue-Zhong" last="Ma">Xue-Zhong Ma</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>University of Toronto Transplantation Institute</s1><s2>Toronto, Ontario, M5G 2N2</s2><s3>CAN</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>University of Toronto Transplantation Institute</wicri:noRegion></affiliation></author><author><name sortKey="Jianhua Zhang" sort="Jianhua Zhang" uniqKey="Jianhua Zhang" last="Jianhua Zhang">JIANHUA ZHANG</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>University of Toronto Transplantation Institute</s1><s2>Toronto, Ontario, M5G 2N2</s2><s3>CAN</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>University of Toronto Transplantation Institute</wicri:noRegion></affiliation></author><author><name sortKey="Shalev, Itay" sort="Shalev, Itay" uniqKey="Shalev I" first="Itay" last="Shalev">Itay Shalev</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>University of Toronto Transplantation Institute</s1><s2>Toronto, Ontario, M5G 2N2</s2><s3>CAN</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>University of Toronto Transplantation Institute</wicri:noRegion></affiliation></author><author><name sortKey="Smith, Robert" sort="Smith, Robert" uniqKey="Smith R" first="Robert" last="Smith">Robert Smith</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>University of Toronto Transplantation Institute</s1><s2>Toronto, Ontario, M5G 2N2</s2><s3>CAN</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>University of Toronto Transplantation Institute</wicri:noRegion></affiliation></author><author><name sortKey="Phillips, Melville J" sort="Phillips, Melville J" uniqKey="Phillips M" first="Melville J." last="Phillips">Melville J. Phillips</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>University of Toronto Transplantation Institute</s1><s2>Toronto, Ontario, M5G 2N2</s2><s3>CAN</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>University of Toronto Transplantation Institute</wicri:noRegion></affiliation></author><author><name sortKey="Levy, Gary A" sort="Levy, Gary A" uniqKey="Levy G" first="Gary A." last="Levy">Gary A. Levy</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>University of Toronto Transplantation Institute</s1><s2>Toronto, Ontario, M5G 2N2</s2><s3>CAN</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>University of Toronto Transplantation Institute</wicri:noRegion></affiliation></author><author><name sortKey="Weiss, Susan R" sort="Weiss, Susan R" uniqKey="Weiss S" first="Susan R." last="Weiss">Susan R. Weiss</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Microbiology, University of Pennsylvania School of Medicine</s1><s2>Philadelphia, Pennsylvania 19104-6076</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Philadelphia, Pennsylvania 19104-6076</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">10-0419994</idno><date when="2010">2010</date><idno type="stanalyst">PASCAL 10-0419994 INIST</idno><idno type="RBID">Pascal:10-0419994</idno><idno type="wicri:Area/PascalFrancis/Corpus">000145</idno><idno type="wicri:Area/PascalFrancis/Curation">000843</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000148</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000148</idno><idno type="wicri:doubleKey">0022-538X:2010:Leibowitz J:genetic:determinants:of</idno><idno type="wicri:Area/Main/Merge">002980</idno><idno type="wicri:Area/Main/Curation">002938</idno><idno type="wicri:Area/Main/Exploration">002938</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Genetic Determinants of Mouse Hepatitis Virus Strain 1 Pneumovirulence</title><author><name sortKey="Leibowitz, Julian L" sort="Leibowitz, Julian L" uniqKey="Leibowitz J" first="Julian L." last="Leibowitz">Julian L. Leibowitz</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Microbial and Molecular Pathogenesis, Texas A&M University System-HSC, College of Medicine</s1><s2>College Station, Texas 77843-1114</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>College Station, Texas 77843-1114</wicri:noRegion></affiliation></author><author><name sortKey="Srinivasa, Rajiv" sort="Srinivasa, Rajiv" uniqKey="Srinivasa R" first="Rajiv" last="Srinivasa">Rajiv Srinivasa</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Microbial and Molecular Pathogenesis, Texas A&M University System-HSC, College of Medicine</s1><s2>College Station, Texas 77843-1114</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>College Station, Texas 77843-1114</wicri:noRegion></affiliation></author><author><name sortKey="Williamson, Shawn T" sort="Williamson, Shawn T" uniqKey="Williamson S" first="Shawn T." last="Williamson">Shawn T. Williamson</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Microbial and Molecular Pathogenesis, Texas A&M University System-HSC, College of Medicine</s1><s2>College Station, Texas 77843-1114</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>College Station, Texas 77843-1114</wicri:noRegion></affiliation></author><author><name sortKey="Ming Ming Chua" sort="Ming Ming Chua" uniqKey="Ming Ming Chua" last="Ming Ming Chua">MING MING CHUA</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Microbiology, University of Pennsylvania School of Medicine</s1><s2>Philadelphia, Pennsylvania 19104-6076</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Philadelphia, Pennsylvania 19104-6076</wicri:noRegion></affiliation></author><author><name sortKey="Mingfeng Liu" sort="Mingfeng Liu" uniqKey="Mingfeng Liu" last="Mingfeng Liu">MINGFENG LIU</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>University of Toronto Transplantation Institute</s1><s2>Toronto, Ontario, M5G 2N2</s2><s3>CAN</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>University of Toronto Transplantation Institute</wicri:noRegion></affiliation></author><author><name sortKey="Samantha Wu" sort="Samantha Wu" uniqKey="Samantha Wu" last="Samantha Wu">SAMANTHA WU</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>University of Toronto Transplantation Institute</s1><s2>Toronto, Ontario, M5G 2N2</s2><s3>CAN</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>University of Toronto Transplantation Institute</wicri:noRegion></affiliation></author><author><name sortKey="Hyojeung Kang" sort="Hyojeung Kang" uniqKey="Hyojeung Kang" last="Hyojeung Kang">HYOJEUNG KANG</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Microbial and Molecular Pathogenesis, Texas A&M University System-HSC, College of Medicine</s1><s2>College Station, Texas 77843-1114</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>College Station, Texas 77843-1114</wicri:noRegion></affiliation></author><author><name sortKey="Ma, Xue Zhong" sort="Ma, Xue Zhong" uniqKey="Ma X" first="Xue-Zhong" last="Ma">Xue-Zhong Ma</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>University of Toronto Transplantation Institute</s1><s2>Toronto, Ontario, M5G 2N2</s2><s3>CAN</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>University of Toronto Transplantation Institute</wicri:noRegion></affiliation></author><author><name sortKey="Jianhua Zhang" sort="Jianhua Zhang" uniqKey="Jianhua Zhang" last="Jianhua Zhang">JIANHUA ZHANG</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>University of Toronto Transplantation Institute</s1><s2>Toronto, Ontario, M5G 2N2</s2><s3>CAN</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>University of Toronto Transplantation Institute</wicri:noRegion></affiliation></author><author><name sortKey="Shalev, Itay" sort="Shalev, Itay" uniqKey="Shalev I" first="Itay" last="Shalev">Itay Shalev</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>University of Toronto Transplantation Institute</s1><s2>Toronto, Ontario, M5G 2N2</s2><s3>CAN</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>University of Toronto Transplantation Institute</wicri:noRegion></affiliation></author><author><name sortKey="Smith, Robert" sort="Smith, Robert" uniqKey="Smith R" first="Robert" last="Smith">Robert Smith</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>University of Toronto Transplantation Institute</s1><s2>Toronto, Ontario, M5G 2N2</s2><s3>CAN</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>University of Toronto Transplantation Institute</wicri:noRegion></affiliation></author><author><name sortKey="Phillips, Melville J" sort="Phillips, Melville J" uniqKey="Phillips M" first="Melville J." last="Phillips">Melville J. Phillips</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>University of Toronto Transplantation Institute</s1><s2>Toronto, Ontario, M5G 2N2</s2><s3>CAN</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>University of Toronto Transplantation Institute</wicri:noRegion></affiliation></author><author><name sortKey="Levy, Gary A" sort="Levy, Gary A" uniqKey="Levy G" first="Gary A." last="Levy">Gary A. Levy</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>University of Toronto Transplantation Institute</s1><s2>Toronto, Ontario, M5G 2N2</s2><s3>CAN</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ><sZ>12 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>University of Toronto Transplantation Institute</wicri:noRegion></affiliation></author><author><name sortKey="Weiss, Susan R" sort="Weiss, Susan R" uniqKey="Weiss S" first="Susan R." last="Weiss">Susan R. Weiss</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Microbiology, University of Pennsylvania School of Medicine</s1><s2>Philadelphia, Pennsylvania 19104-6076</s2><s3>USA</s3><sZ>4 aut.</sZ><sZ>14 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Philadelphia, Pennsylvania 19104-6076</wicri:noRegion></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="2010">2010</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>Genetics</term><term>Hepatitis</term><term>Mouse</term><term>Strain</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Souris</term><term>Génétique</term><term>Souche</term><term>Hépatite</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Génétique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">We report here investigation into the genetic basis of mouse hepatitis virus strain 1 (MHV-1) pneumovirulence. Sequencing of the 3' one-third of the MHV-1 genome demonstrated that the genetic organization of MHV-1 was similar to that of other strains of MHV. The hemagglutinin esterase (HE) protein was truncated, and reverse transcription-PCR (RT-PCR) studies confirmed previous work that suggested that the MHV-1 HE is a pseudogene. Targeted recombination was used to select chimeric viruses containing either the MHV-1 S gene or genes encoding all of the MHV-1 structural proteins, on an MHV-A59 background. Challenge studies in mice demonstrated that expression of the MHV-1 S gene within the MHV-A59 background (rA59/S<sub>MHV-1</sub>) increased the pneumovirulence of MHV-A59, and mice infected with this recombinant virus developed pulmonary lesions that were similar to those observed with MHV-1, although rA59/S<sub>MHV-1</sub> was significantly less virulent. Chimeras containing all of the MHV-1 structural genes on an MHV-A59 background were able to reproduce the severe acute respiratory syndrome (SARS)-like pathology observed with MHV-1 and reproducibly increased pneumovirulence relative to rA59/S<sub>MHV-1</sub> but were still much less virulent than MHV-1. These data suggest that important determinants of pneumopathogenicity are contained within the 3' one-third of the MHV-1 genome, but additional important virulence factors must be encoded in the genome upstream of the S gene. The severity of the pulmonary lesions observed correlates better with elevated levels of inflammatory cytokines than with viral replication in the lungs, suggesting that pulmonary disease has an important immunological component.</div></front></TEI><affiliations><list><country><li>Canada</li><li>États-Unis</li></country></list><tree><country name="États-Unis"><noRegion><name sortKey="Leibowitz, Julian L" sort="Leibowitz, Julian L" uniqKey="Leibowitz J" first="Julian L." last="Leibowitz">Julian L. Leibowitz</name></noRegion><name sortKey="Hyojeung Kang" sort="Hyojeung Kang" uniqKey="Hyojeung Kang" last="Hyojeung Kang">HYOJEUNG KANG</name><name sortKey="Ming Ming Chua" sort="Ming Ming Chua" uniqKey="Ming Ming Chua" last="Ming Ming Chua">MING MING CHUA</name><name sortKey="Srinivasa, Rajiv" sort="Srinivasa, Rajiv" uniqKey="Srinivasa R" first="Rajiv" last="Srinivasa">Rajiv Srinivasa</name><name sortKey="Weiss, Susan R" sort="Weiss, Susan R" uniqKey="Weiss S" first="Susan R." last="Weiss">Susan R. Weiss</name><name sortKey="Williamson, Shawn T" sort="Williamson, Shawn T" uniqKey="Williamson S" first="Shawn T." last="Williamson">Shawn T. Williamson</name></country><country name="Canada"><noRegion><name sortKey="Mingfeng Liu" sort="Mingfeng Liu" uniqKey="Mingfeng Liu" last="Mingfeng Liu">MINGFENG LIU</name></noRegion><name sortKey="Jianhua Zhang" sort="Jianhua Zhang" uniqKey="Jianhua Zhang" last="Jianhua Zhang">JIANHUA ZHANG</name><name sortKey="Levy, Gary A" sort="Levy, Gary A" uniqKey="Levy G" first="Gary A." last="Levy">Gary A. Levy</name><name sortKey="Ma, Xue Zhong" sort="Ma, Xue Zhong" uniqKey="Ma X" first="Xue-Zhong" last="Ma">Xue-Zhong Ma</name><name sortKey="Phillips, Melville J" sort="Phillips, Melville J" uniqKey="Phillips M" first="Melville J." last="Phillips">Melville J. Phillips</name><name sortKey="Samantha Wu" sort="Samantha Wu" uniqKey="Samantha Wu" last="Samantha Wu">SAMANTHA WU</name><name sortKey="Shalev, Itay" sort="Shalev, Itay" uniqKey="Shalev I" first="Itay" last="Shalev">Itay Shalev</name><name sortKey="Smith, Robert" sort="Smith, Robert" uniqKey="Smith R" first="Robert" last="Smith">Robert Smith</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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