Molecular determinants of severe acute respiratory syndrome coronavirus pathogenesis and virulence in young and aged mouse models of human disease.
Identifieur interne : 001450 ( PubMed/Corpus ); précédent : 001449; suivant : 001451Molecular determinants of severe acute respiratory syndrome coronavirus pathogenesis and virulence in young and aged mouse models of human disease.
Auteurs : Matthew Frieman ; Boyd Yount ; Sudhakar Agnihothram ; Carly Page ; Eric Donaldson ; Anjeanette Roberts ; Leatrice Vogel ; Becky Woodruff ; Diana Scorpio ; Kanta Subbarao ; Ralph S. BaricSource :
- Journal of virology [ 1098-5514 ] ; 2012.
English descriptors
- KwdEn :
- Age Factors, Animals, Cell Line, Disease Models, Animal, Female, Humans, Mice, Mice, Inbred BALB C, Mutation, Reverse Genetics, SARS Virus (genetics), SARS Virus (isolation & purification), SARS Virus (metabolism), SARS Virus (pathogenicity), Severe Acute Respiratory Syndrome (mortality), Severe Acute Respiratory Syndrome (pathology), Severe Acute Respiratory Syndrome (virology), Viral Proteins (genetics), Viral Proteins (metabolism), Virulence.
- MESH :
- chemical , genetics : Viral Proteins.
- genetics : SARS Virus.
- isolation & purification : SARS Virus.
- metabolism : SARS Virus, Viral Proteins.
- mortality : Severe Acute Respiratory Syndrome.
- pathogenicity : SARS Virus.
- pathology : Severe Acute Respiratory Syndrome.
- virology : Severe Acute Respiratory Syndrome.
- Age Factors, Animals, Cell Line, Disease Models, Animal, Female, Humans, Mice, Mice, Inbred BALB C, Mutation, Reverse Genetics, Virulence.
Abstract
SARS coronavirus (SARS-CoV) causes severe acute respiratory tract disease characterized by diffuse alveolar damage and hyaline membrane formation. This pathology often progresses to acute respiratory distress (such as acute respiratory distress syndrome [ARDS]) and atypical pneumonia in humans, with characteristic age-related mortality rates approaching 50% or more in immunosenescent populations. The molecular basis for the extreme virulence of SARS-CoV remains elusive. Since young and aged (1-year-old) mice do not develop severe clinical disease following infection with wild-type SARS-CoV, a mouse-adapted strain of SARS-CoV (called MA15) was developed and was shown to cause lethal infection in these animals. To understand the genetic contributions to the increased pathogenesis of MA15 in rodents, we used reverse genetics and evaluated the virulence of panels of derivative viruses encoding various combinations of mouse-adapted mutations. We found that mutations in the viral spike (S) glycoprotein and, to a much less rigorous extent, in the nsp9 nonstructural protein, were primarily associated with the acquisition of virulence in young animals. The mutations in S likely increase recognition of the mouse angiotensin-converting enzyme 2 (ACE2) receptor not only in MA15 but also in two additional, independently isolated mouse-adapted SARS-CoVs. In contrast to the findings for young animals, mutations to revert to the wild-type sequence in nsp9 and the S glycoprotein were not sufficient to significantly attenuate the virus compared to other combinations of mouse-adapted mutations in 12-month-old mice. This panel of SARS-CoVs provides novel reagents that we have used to further our understanding of differential, age-related pathogenic mechanisms in mouse models of human disease.
DOI: 10.1128/JVI.05957-11
PubMed: 22072787
Links to Exploration step
pubmed:22072787Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Molecular determinants of severe acute respiratory syndrome coronavirus pathogenesis and virulence in young and aged mouse models of human disease.</title><author><name sortKey="Frieman, Matthew" sort="Frieman, Matthew" uniqKey="Frieman M" first="Matthew" last="Frieman">Matthew Frieman</name><affiliation><nlm:affiliation>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA. mfrieman@som.umaryland.edu</nlm:affiliation></affiliation></author><author><name sortKey="Yount, Boyd" sort="Yount, Boyd" uniqKey="Yount B" first="Boyd" last="Yount">Boyd Yount</name></author><author><name sortKey="Agnihothram, Sudhakar" sort="Agnihothram, Sudhakar" uniqKey="Agnihothram S" first="Sudhakar" last="Agnihothram">Sudhakar Agnihothram</name></author><author><name sortKey="Page, Carly" sort="Page, Carly" uniqKey="Page C" first="Carly" last="Page">Carly Page</name></author><author><name sortKey="Donaldson, Eric" sort="Donaldson, Eric" uniqKey="Donaldson E" first="Eric" last="Donaldson">Eric Donaldson</name></author><author><name sortKey="Roberts, Anjeanette" sort="Roberts, Anjeanette" uniqKey="Roberts A" first="Anjeanette" last="Roberts">Anjeanette Roberts</name></author><author><name sortKey="Vogel, Leatrice" sort="Vogel, Leatrice" uniqKey="Vogel L" first="Leatrice" last="Vogel">Leatrice Vogel</name></author><author><name sortKey="Woodruff, Becky" sort="Woodruff, Becky" uniqKey="Woodruff B" first="Becky" last="Woodruff">Becky Woodruff</name></author><author><name sortKey="Scorpio, Diana" sort="Scorpio, Diana" uniqKey="Scorpio D" first="Diana" last="Scorpio">Diana Scorpio</name></author><author><name sortKey="Subbarao, Kanta" sort="Subbarao, Kanta" uniqKey="Subbarao K" first="Kanta" last="Subbarao">Kanta Subbarao</name></author><author><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S" last="Baric">Ralph S. Baric</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2012">2012</date><idno type="RBID">pubmed:22072787</idno><idno type="pmid">22072787</idno><idno type="doi">10.1128/JVI.05957-11</idno><idno type="wicri:Area/PubMed/Corpus">001450</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001450</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Molecular determinants of severe acute respiratory syndrome coronavirus pathogenesis and virulence in young and aged mouse models of human disease.</title><author><name sortKey="Frieman, Matthew" sort="Frieman, Matthew" uniqKey="Frieman M" first="Matthew" last="Frieman">Matthew Frieman</name><affiliation><nlm:affiliation>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA. mfrieman@som.umaryland.edu</nlm:affiliation></affiliation></author><author><name sortKey="Yount, Boyd" sort="Yount, Boyd" uniqKey="Yount B" first="Boyd" last="Yount">Boyd Yount</name></author><author><name sortKey="Agnihothram, Sudhakar" sort="Agnihothram, Sudhakar" uniqKey="Agnihothram S" first="Sudhakar" last="Agnihothram">Sudhakar Agnihothram</name></author><author><name sortKey="Page, Carly" sort="Page, Carly" uniqKey="Page C" first="Carly" last="Page">Carly Page</name></author><author><name sortKey="Donaldson, Eric" sort="Donaldson, Eric" uniqKey="Donaldson E" first="Eric" last="Donaldson">Eric Donaldson</name></author><author><name sortKey="Roberts, Anjeanette" sort="Roberts, Anjeanette" uniqKey="Roberts A" first="Anjeanette" last="Roberts">Anjeanette Roberts</name></author><author><name sortKey="Vogel, Leatrice" sort="Vogel, Leatrice" uniqKey="Vogel L" first="Leatrice" last="Vogel">Leatrice Vogel</name></author><author><name sortKey="Woodruff, Becky" sort="Woodruff, Becky" uniqKey="Woodruff B" first="Becky" last="Woodruff">Becky Woodruff</name></author><author><name sortKey="Scorpio, Diana" sort="Scorpio, Diana" uniqKey="Scorpio D" first="Diana" last="Scorpio">Diana Scorpio</name></author><author><name sortKey="Subbarao, Kanta" sort="Subbarao, Kanta" uniqKey="Subbarao K" first="Kanta" last="Subbarao">Kanta Subbarao</name></author><author><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S" last="Baric">Ralph S. Baric</name></author></analytic><series><title level="j">Journal of virology</title><idno type="eISSN">1098-5514</idno><imprint><date when="2012" type="published">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Age Factors</term><term>Animals</term><term>Cell Line</term><term>Disease Models, Animal</term><term>Female</term><term>Humans</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Mutation</term><term>Reverse Genetics</term><term>SARS Virus (genetics)</term><term>SARS Virus (isolation & purification)</term><term>SARS Virus (metabolism)</term><term>SARS Virus (pathogenicity)</term><term>Severe Acute Respiratory Syndrome (mortality)</term><term>Severe Acute Respiratory Syndrome (pathology)</term><term>Severe Acute Respiratory Syndrome (virology)</term><term>Viral Proteins (genetics)</term><term>Viral Proteins (metabolism)</term><term>Virulence</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Viral Proteins</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="isolation & purification" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>SARS Virus</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" qualifier="mortality" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Age Factors</term><term>Animals</term><term>Cell Line</term><term>Disease Models, Animal</term><term>Female</term><term>Humans</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Mutation</term><term>Reverse Genetics</term><term>Virulence</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">SARS coronavirus (SARS-CoV) causes severe acute respiratory tract disease characterized by diffuse alveolar damage and hyaline membrane formation. This pathology often progresses to acute respiratory distress (such as acute respiratory distress syndrome [ARDS]) and atypical pneumonia in humans, with characteristic age-related mortality rates approaching 50% or more in immunosenescent populations. The molecular basis for the extreme virulence of SARS-CoV remains elusive. Since young and aged (1-year-old) mice do not develop severe clinical disease following infection with wild-type SARS-CoV, a mouse-adapted strain of SARS-CoV (called MA15) was developed and was shown to cause lethal infection in these animals. To understand the genetic contributions to the increased pathogenesis of MA15 in rodents, we used reverse genetics and evaluated the virulence of panels of derivative viruses encoding various combinations of mouse-adapted mutations. We found that mutations in the viral spike (S) glycoprotein and, to a much less rigorous extent, in the nsp9 nonstructural protein, were primarily associated with the acquisition of virulence in young animals. The mutations in S likely increase recognition of the mouse angiotensin-converting enzyme 2 (ACE2) receptor not only in MA15 but also in two additional, independently isolated mouse-adapted SARS-CoVs. In contrast to the findings for young animals, mutations to revert to the wild-type sequence in nsp9 and the S glycoprotein were not sufficient to significantly attenuate the virus compared to other combinations of mouse-adapted mutations in 12-month-old mice. This panel of SARS-CoVs provides novel reagents that we have used to further our understanding of differential, age-related pathogenic mechanisms in mouse models of human disease.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">22072787</PMID><DateCompleted><Year>2012</Year><Month>02</Month><Day>22</Day></DateCompleted><DateRevised><Year>2018</Year><Month>11</Month><Day>13</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1098-5514</ISSN><JournalIssue CitedMedium="Internet"><Volume>86</Volume><Issue>2</Issue><PubDate><Year>2012</Year><Month>Jan</Month></PubDate></JournalIssue><Title>Journal of virology</Title><ISOAbbreviation>J. Virol.</ISOAbbreviation></Journal><ArticleTitle>Molecular determinants of severe acute respiratory syndrome coronavirus pathogenesis and virulence in young and aged mouse models of human disease.</ArticleTitle><Pagination><MedlinePgn>884-97</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1128/JVI.05957-11</ELocationID><Abstract><AbstractText>SARS coronavirus (SARS-CoV) causes severe acute respiratory tract disease characterized by diffuse alveolar damage and hyaline membrane formation. This pathology often progresses to acute respiratory distress (such as acute respiratory distress syndrome [ARDS]) and atypical pneumonia in humans, with characteristic age-related mortality rates approaching 50% or more in immunosenescent populations. The molecular basis for the extreme virulence of SARS-CoV remains elusive. Since young and aged (1-year-old) mice do not develop severe clinical disease following infection with wild-type SARS-CoV, a mouse-adapted strain of SARS-CoV (called MA15) was developed and was shown to cause lethal infection in these animals. To understand the genetic contributions to the increased pathogenesis of MA15 in rodents, we used reverse genetics and evaluated the virulence of panels of derivative viruses encoding various combinations of mouse-adapted mutations. We found that mutations in the viral spike (S) glycoprotein and, to a much less rigorous extent, in the nsp9 nonstructural protein, were primarily associated with the acquisition of virulence in young animals. The mutations in S likely increase recognition of the mouse angiotensin-converting enzyme 2 (ACE2) receptor not only in MA15 but also in two additional, independently isolated mouse-adapted SARS-CoVs. In contrast to the findings for young animals, mutations to revert to the wild-type sequence in nsp9 and the S glycoprotein were not sufficient to significantly attenuate the virus compared to other combinations of mouse-adapted mutations in 12-month-old mice. This panel of SARS-CoVs provides novel reagents that we have used to further our understanding of differential, age-related pathogenic mechanisms in mouse models of human disease.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Frieman</LastName><ForeName>Matthew</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA. mfrieman@som.umaryland.edu</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yount</LastName><ForeName>Boyd</ForeName><Initials>B</Initials></Author><Author ValidYN="Y"><LastName>Agnihothram</LastName><ForeName>Sudhakar</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Page</LastName><ForeName>Carly</ForeName><Initials>C</Initials></Author><Author ValidYN="Y"><LastName>Donaldson</LastName><ForeName>Eric</ForeName><Initials>E</Initials></Author><Author ValidYN="Y"><LastName>Roberts</LastName><ForeName>Anjeanette</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Vogel</LastName><ForeName>Leatrice</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Woodruff</LastName><ForeName>Becky</ForeName><Initials>B</Initials></Author><Author ValidYN="Y"><LastName>Scorpio</LastName><ForeName>Diana</ForeName><Initials>D</Initials></Author><Author ValidYN="Y"><LastName>Subbarao</LastName><ForeName>Kanta</ForeName><Initials>K</Initials></Author><Author ValidYN="Y"><LastName>Baric</LastName><ForeName>Ralph S</ForeName><Initials>RS</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>F32 AI066542</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AI075297</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>T32 AI007540</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D003160">Comparative Study</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2011</Year><Month>11</Month><Day>09</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Virol</MedlineTA><NlmUniqueID>0113724</NlmUniqueID><ISSNLinking>0022-538X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D014764">Viral Proteins</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000367" MajorTopicYN="N">Age Factors</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002460" MajorTopicYN="N">Cell Line</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004195" MajorTopicYN="Y">Disease Models, Animal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="Y">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008807" MajorTopicYN="N">Mice, Inbred BALB C</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009154" MajorTopicYN="N">Mutation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D059386" MajorTopicYN="N">Reverse Genetics</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D045473" MajorTopicYN="N">SARS Virus</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000302" MajorTopicYN="N">isolation & purification</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000472" MajorTopicYN="Y">pathogenicity</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D045169" MajorTopicYN="N">Severe Acute Respiratory Syndrome</DescriptorName><QualifierName UI="Q000401" MajorTopicYN="N">mortality</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName><QualifierName UI="Q000821" MajorTopicYN="Y">virology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014764" MajorTopicYN="N">Viral Proteins</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014774" MajorTopicYN="N">Virulence</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2011</Year><Month>11</Month><Day>11</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2011</Year><Month>11</Month><Day>11</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2012</Year><Month>2</Month><Day>23</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">22072787</ArticleId><ArticleId IdType="pii">JVI.05957-11</ArticleId><ArticleId IdType="doi">10.1128/JVI.05957-11</ArticleId><ArticleId IdType="pmc">PMC3255850</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>J Virol. 2004 Sep;78(18):9977-86</Citation><ArticleIdList><ArticleId IdType="pubmed">15331731</ArticleId></ArticleIdList></Reference><Reference><Citation>Proc Natl Acad Sci U S A. 2005 Feb 15;102(7):2430-5</Citation><ArticleIdList><ArticleId IdType="pubmed">15695582</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virol. 2005 Dec;79(24):15189-98</Citation><ArticleIdList><ArticleId IdType="pubmed">16306590</ArticleId></ArticleIdList></Reference><Reference><Citation>Virus Res. 2008 Apr;133(1):20-32</Citation><ArticleIdList><ArticleId IdType="pubmed">17499378</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virol. 2008 Mar;82(5):2274-85</Citation><ArticleIdList><ArticleId IdType="pubmed">18094188</ArticleId></ArticleIdList></Reference><Reference><Citation>PLoS Med. 2006 Feb;3(2):e27</Citation><ArticleIdList><ArticleId IdType="pubmed">16379499</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virol. 2004 May;78(9):4552-60</Citation><ArticleIdList><ArticleId IdType="pubmed">15078936</ArticleId></ArticleIdList></Reference><Reference><Citation>N Engl J Med. 2003 May 15;348(20):1967-76</Citation><ArticleIdList><ArticleId IdType="pubmed">12690091</ArticleId></ArticleIdList></Reference><Reference><Citation>EMBO J. 2005 Apr 20;24(8):1634-43</Citation><ArticleIdList><ArticleId IdType="pubmed">15791205</ArticleId></ArticleIdList></Reference><Reference><Citation>Biochem Biophys Res Commun. 2003 Dec 26;312(4):1159-64</Citation><ArticleIdList><ArticleId IdType="pubmed">14651994</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virol. 2008 Jun;82(11):5137-44</Citation><ArticleIdList><ArticleId IdType="pubmed">18367528</ArticleId></ArticleIdList></Reference><Reference><Citation>PLoS Pathog. 2008 Dec;4(12):e1000240</Citation><ArticleIdList><ArticleId IdType="pubmed">19079579</ArticleId></ArticleIdList></Reference><Reference><Citation>Virology. 2009 Dec 20;395(2):210-22</Citation><ArticleIdList><ArticleId IdType="pubmed">19853271</ArticleId></ArticleIdList></Reference><Reference><Citation>Science. 2004 Mar 12;303(5664):1666-9</Citation><ArticleIdList><ArticleId IdType="pubmed">14752165</ArticleId></ArticleIdList></Reference><Reference><Citation>Adv Exp Med Biol. 2006;581:285-8</Citation><ArticleIdList><ArticleId IdType="pubmed">17037544</ArticleId></ArticleIdList></Reference><Reference><Citation>Hong Kong Med J. 2010;16(5 Suppl 4):29-33</Citation><ArticleIdList><ArticleId IdType="pubmed">20864745</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virol. 2007 Jul;81(14):7410-23</Citation><ArticleIdList><ArticleId IdType="pubmed">17507479</ArticleId></ArticleIdList></Reference><Reference><Citation>Lancet. 2003 May 24;361(9371):1767-72</Citation><ArticleIdList><ArticleId IdType="pubmed">12781535</ArticleId></ArticleIdList></Reference><Reference><Citation>PLoS Pathog. 2010 Apr;6(4):e1000849</Citation><ArticleIdList><ArticleId IdType="pubmed">20386712</ArticleId></ArticleIdList></Reference><Reference><Citation>Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12995-3000</Citation><ArticleIdList><ArticleId IdType="pubmed">14569023</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virol. 2007 Nov;81(22):12135-44</Citation><ArticleIdList><ArticleId IdType="pubmed">17804504</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virol. 2004 Oct;78(19):10628-35</Citation><ArticleIdList><ArticleId IdType="pubmed">15367630</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virol. 2008 May;82(9):4471-9</Citation><ArticleIdList><ArticleId IdType="pubmed">18305050</ArticleId></ArticleIdList></Reference><Reference><Citation>Proc Natl Acad Sci U S A. 2004 Mar 16;101(11):3792-6</Citation><ArticleIdList><ArticleId IdType="pubmed">15007178</ArticleId></ArticleIdList></Reference><Reference><Citation>Histopathology. 2004 Aug;45(2):119-24</Citation><ArticleIdList><ArticleId IdType="pubmed">15279629</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virol. 2008 Jul;82(14):6984-91</Citation><ArticleIdList><ArticleId IdType="pubmed">18448527</ArticleId></ArticleIdList></Reference><Reference><Citation>J Gen Virol. 1980 Jan;46(1):1-13</Citation><ArticleIdList><ArticleId IdType="pubmed">6766176</ArticleId></ArticleIdList></Reference><Reference><Citation>Science. 2005 Sep 16;309(5742):1864-8</Citation><ArticleIdList><ArticleId IdType="pubmed">16166518</ArticleId></ArticleIdList></Reference><Reference><Citation>Adv Exp Med Biol. 2001;494:101-7</Citation><ArticleIdList><ArticleId IdType="pubmed">11774452</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virol. 2009 Dec;83(24):12998-3008</Citation><ArticleIdList><ArticleId IdType="pubmed">19828617</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virol. 2005 May;79(9):5833-8</Citation><ArticleIdList><ArticleId IdType="pubmed">15827197</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virol. 2009 Jul;83(13):6689-705</Citation><ArticleIdList><ArticleId IdType="pubmed">19369340</ArticleId></ArticleIdList></Reference><Reference><Citation>Infect Immun. 1981 Jan;31(1):334-8</Citation><ArticleIdList><ArticleId IdType="pubmed">6111538</ArticleId></ArticleIdList></Reference><Reference><Citation>Cell. 1990 Oct 19;63(2):353-62</Citation><ArticleIdList><ArticleId IdType="pubmed">2170026</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virol. 1996 Oct;70(10):6673-81</Citation><ArticleIdList><ArticleId IdType="pubmed">8794303</ArticleId></ArticleIdList></Reference><Reference><Citation>J Gen Virol. 1997 Dec;78 ( Pt 12):3207-15</Citation><ArticleIdList><ArticleId IdType="pubmed">9400971</ArticleId></ArticleIdList></Reference><Reference><Citation>Hum Pathol. 2006 Apr;37(4):381-90</Citation><ArticleIdList><ArticleId IdType="pubmed">16564911</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virol. 2004 Dec;78(24):13600-12</Citation><ArticleIdList><ArticleId IdType="pubmed">15564471</ArticleId></ArticleIdList></Reference><Reference><Citation>PLoS Pathog. 2009 Oct;5(10):e1000636</Citation><ArticleIdList><ArticleId IdType="pubmed">19851468</ArticleId></ArticleIdList></Reference><Reference><Citation>RNA Biol. 2011 Mar-Apr;8(2):270-9</Citation><ArticleIdList><ArticleId IdType="pubmed">21593585</ArticleId></ArticleIdList></Reference><Reference><Citation>Am J Trop Med Hyg. 1985 Mar;34(2):388-95</Citation><ArticleIdList><ArticleId IdType="pubmed">2858987</ArticleId></ArticleIdList></Reference><Reference><Citation>Lab Anim Sci. 1990 Sep;40(5):481-5</Citation><ArticleIdList><ArticleId IdType="pubmed">2170746</ArticleId></ArticleIdList></Reference><Reference><Citation>J Immunol. 2004 Sep 15;173(6):4030-9</Citation><ArticleIdList><ArticleId IdType="pubmed">15356152</ArticleId></ArticleIdList></Reference><Reference><Citation>Science. 2003 Oct 10;302(5643):276-8</Citation><ArticleIdList><ArticleId IdType="pubmed">12958366</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virol. 2004 Jun;78(11):5619-32</Citation><ArticleIdList><ArticleId IdType="pubmed">15140959</ArticleId></ArticleIdList></Reference><Reference><Citation>Emerg Infect Dis. 2004 Sep;10(9):1550-7</Citation><ArticleIdList><ArticleId IdType="pubmed">15498155</ArticleId></ArticleIdList></Reference><Reference><Citation>Structure. 2004 Feb;12(2):341-53</Citation><ArticleIdList><ArticleId IdType="pubmed">14962394</ArticleId></ArticleIdList></Reference><Reference><Citation>Virology. 2004 Feb 20;319(2):262-73</Citation><ArticleIdList><ArticleId IdType="pubmed">14980486</ArticleId></ArticleIdList></Reference><Reference><Citation>Curr Opin Pharmacol. 2006 Jun;6(3):271-6</Citation><ArticleIdList><ArticleId IdType="pubmed">16581295</ArticleId></ArticleIdList></Reference><Reference><Citation>Cell. 2003 Jun 13;113(6):701-2</Citation><ArticleIdList><ArticleId IdType="pubmed">12809601</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virol. 2005 Mar;79(6):3391-400</Citation><ArticleIdList><ArticleId IdType="pubmed">15731233</ArticleId></ArticleIdList></Reference><Reference><Citation>Science. 2005 Sep 16;309(5742):1822-3</Citation><ArticleIdList><ArticleId IdType="pubmed">16166506</ArticleId></ArticleIdList></Reference><Reference><Citation>Lancet. 2003 May 24;361(9371):1773-8</Citation><ArticleIdList><ArticleId IdType="pubmed">12781536</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virol. 2010 Nov;84(21):11297-309</Citation><ArticleIdList><ArticleId IdType="pubmed">20702617</ArticleId></ArticleIdList></Reference><Reference><Citation>Science. 2003 May 30;300(5624):1394-9</Citation><ArticleIdList><ArticleId IdType="pubmed">12730500</ArticleId></ArticleIdList></Reference><Reference><Citation>Science. 1949 Aug 19;110(2851):184</Citation><ArticleIdList><ArticleId IdType="pubmed">17779824</ArticleId></ArticleIdList></Reference><Reference><Citation>PLoS Pathog. 2007 Jan;3(1):e5</Citation><ArticleIdList><ArticleId IdType="pubmed">17222058</ArticleId></ArticleIdList></Reference><Reference><Citation>N Engl J Med. 2003 May 15;348(20):1953-66</Citation><ArticleIdList><ArticleId IdType="pubmed">12690092</ArticleId></ArticleIdList></Reference><Reference><Citation>Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4659-63</Citation><ArticleIdList><ArticleId IdType="pubmed">9114047</ArticleId></ArticleIdList></Reference><Reference><Citation>Curr Opin Immunol. 2005 Aug;17(4):404-10</Citation><ArticleIdList><ArticleId IdType="pubmed">15950449</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virol. 2007 Jan;81(2):813-21</Citation><ArticleIdList><ArticleId IdType="pubmed">17079315</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virol. 2008 Sep;82(17):8721-32</Citation><ArticleIdList><ArticleId IdType="pubmed">18579604</ArticleId></ArticleIdList></Reference><Reference><Citation>PLoS Pathog. 2010 May;6(5):e1000896</Citation><ArticleIdList><ArticleId IdType="pubmed">20463816</ArticleId></ArticleIdList></Reference><Reference><Citation>N Engl J Med. 2003 Dec 18;349(25):2431-41</Citation><ArticleIdList><ArticleId IdType="pubmed">14681510</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virol. 1987 Sep;61(9):2917-20</Citation><ArticleIdList><ArticleId IdType="pubmed">3039178</ArticleId></ArticleIdList></Reference><Reference><Citation>J Biol Chem. 2004 Jan 30;279(5):3197-201</Citation><ArticleIdList><ArticleId IdType="pubmed">14670965</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virol. 2009 Jul;83(14):7062-74</Citation><ArticleIdList><ArticleId IdType="pubmed">19420084</ArticleId></ArticleIdList></Reference><Reference><Citation>Proc Natl Acad Sci U S A. 2005 Jun 7;102(23):8275-80</Citation><ArticleIdList><ArticleId IdType="pubmed">15919828</ArticleId></ArticleIdList></Reference><Reference><Citation>Can J Infect Dis Med Microbiol. 2006 Nov;17(6):330-6</Citation><ArticleIdList><ArticleId IdType="pubmed">18382647</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virol. 2004 Mar;78(6):2701-10</Citation><ArticleIdList><ArticleId IdType="pubmed">14990690</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virol. 2011 Jan;85(1):217-30</Citation><ArticleIdList><ArticleId IdType="pubmed">20980507</ArticleId></ArticleIdList></Reference><Reference><Citation>PLoS Pathog. 2006 Jul;2(7):e73</Citation><ArticleIdList><ArticleId IdType="pubmed">16848640</ArticleId></ArticleIdList></Reference><Reference><Citation>J Gen Virol. 2001 Jun;82(Pt 6):1365-73</Citation><ArticleIdList><ArticleId IdType="pubmed">11369881</ArticleId></ArticleIdList></Reference><Reference><Citation>Nucleic Acids Res. 2010 Nov;38(21):7626-36</Citation><ArticleIdList><ArticleId IdType="pubmed">20671029</ArticleId></ArticleIdList></Reference><Reference><Citation>Proc Natl Acad Sci U S A. 2000 Sep 12;97(19):10578-83</Citation><ArticleIdList><ArticleId IdType="pubmed">10973478</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/PubMed/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001450 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/PubMed/Corpus/biblio.hfd -nk 001450 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= SrasV1
|flux= PubMed
|étape= Corpus
|type= RBID
|clé= pubmed:22072787
|texte= Molecular determinants of severe acute respiratory syndrome coronavirus pathogenesis and virulence in young and aged mouse models of human disease.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/PubMed/Corpus/RBID.i -Sk "pubmed:22072787" \
| HfdSelect -Kh $EXPLOR_AREA/Data/PubMed/Corpus/biblio.hfd \
| NlmPubMed2Wicri -a SrasV1
| This area was generated with Dilib version V0.6.33. |  |