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Lethal infection of K18-hACE2 mice infected with severe acute respiratory syndrome coronavirus

Identifieur interne : 003B55 ( Main/Exploration ); précédent : 003B54; suivant : 003B56

Lethal infection of K18-hACE2 mice infected with severe acute respiratory syndrome coronavirus

Auteurs : Paul B. Jr Mccray [États-Unis] ; Lecia Pewe [États-Unis] ; Christine Wohlford-Lenane [États-Unis] ; Melissa Hickey [États-Unis] ; Lori Manzel [États-Unis] ; LEI SHI [États-Unis] ; Jason Netland [États-Unis] ; HONG PENG JIA [États-Unis] ; Carmen Halabi [États-Unis] ; Curt D. Sigmund [États-Unis] ; David K. Meyerholz [États-Unis] ; Patricia Kirby [États-Unis] ; Dwight C. Look [États-Unis] ; Stanley Perlman [États-Unis]

Source :

RBID : Pascal:07-0182099

Descripteurs français

English descriptors

Abstract

The severe acute respiratory syndrome (SARS), caused by a novel coronavirus (SARS-CoV), resulted in substantial morbidity, mortality, and economic losses during the 2003 epidemic. While SARS-CoV infection has not recurred to a significant extent since 2003, it still remains a potential threat. Understanding of SARS and development of therapeutic approaches have been hampered by the absence of an animal model that mimics the human disease and is reproducible. Here we show that transgenic mice that express the SARS-CoV receptor (human angiotensin-converting enzyme 2 [hACE2]) in airway and other epithelia develop a rapidly lethal infection after intranasal inoculation with a human strain of the virus. Infection begins in airway epithelia, with subsequent alveolar involvement and extrapulmonary virus spread to the brain. Infection results in macrophage and lymphocyte infiltration in the lungs and upregulation of proinflammatory cytokines and chemokines in both the lung and the brain. This model of lethal infection with SARS-CoV should be useful for studies of pathogenesis and for the development of antiviral therapies.


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<name sortKey="Halabi, Carmen" sort="Halabi, Carmen" uniqKey="Halabi C" first="Carmen" last="Halabi">Carmen Halabi</name>
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<inist:fA14 i1="02">
<s1>Department of Genetics, University of Iowa</s1>
<s2>Iowa City, Iowa 52242</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName>
<settlement type="city">Iowa City</settlement>
<region type="state">Iowa</region>
</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 52242</s2>
<s3>USA</s3>
<sZ>2 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName>
<settlement type="city">Iowa City</settlement>
<region type="state">Iowa</region>
</placeName>
<orgName type="university">Université de l'Iowa</orgName>
</affiliation>
</author>
<author>
<name sortKey="Sigmund, Curt D" sort="Sigmund, Curt D" uniqKey="Sigmund C" first="Curt D." last="Sigmund">Curt D. Sigmund</name>
<affiliation wicri:level="4">
<inist:fA14 i1="02">
<s1>Department of Genetics, University of Iowa</s1>
<s2>Iowa City, Iowa 52242</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName>
<settlement type="city">Iowa City</settlement>
<region type="state">Iowa</region>
</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 52242</s2>
<s3>USA</s3>
<sZ>2 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName>
<settlement type="city">Iowa City</settlement>
<region type="state">Iowa</region>
</placeName>
<orgName type="university">Université de l'Iowa</orgName>
</affiliation>
</author>
<author>
<name sortKey="Meyerholz, David K" sort="Meyerholz, David K" uniqKey="Meyerholz D" first="David K." last="Meyerholz">David K. Meyerholz</name>
<affiliation wicri:level="4">
<inist:fA14 i1="06">
<s1>Department of Pathology, University of Iowa</s1>
<s2>Iowa City, Iowa 52242</s2>
<s3>USA</s3>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName>
<settlement type="city">Iowa City</settlement>
<region type="state">Iowa</region>
</placeName>
<orgName type="university">Université de l'Iowa</orgName>
</affiliation>
</author>
<author>
<name sortKey="Kirby, Patricia" sort="Kirby, Patricia" uniqKey="Kirby P" first="Patricia" last="Kirby">Patricia Kirby</name>
<affiliation wicri:level="4">
<inist:fA14 i1="06">
<s1>Department of Pathology, University of Iowa</s1>
<s2>Iowa City, Iowa 52242</s2>
<s3>USA</s3>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName>
<settlement type="city">Iowa City</settlement>
<region type="state">Iowa</region>
</placeName>
<orgName type="university">Université de l'Iowa</orgName>
</affiliation>
</author>
<author>
<name sortKey="Look, Dwight C" sort="Look, Dwight C" uniqKey="Look D" first="Dwight C." last="Look">Dwight C. Look</name>
<affiliation wicri:level="4">
<inist:fA14 i1="04">
<s1>Department of Internal Medicine, University of Iowa</s1>
<s2>Iowa City, Iowa 52242</s2>
<s3>USA</s3>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName>
<settlement type="city">Iowa City</settlement>
<region type="state">Iowa</region>
</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="01">
<s1>Department of Pediatrics, University of Iowa</s1>
<s2>Iowa City, Iowa 52242</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName>
<settlement type="city">Iowa City</settlement>
<region type="state">Iowa</region>
</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 52242</s2>
<s3>USA</s3>
<sZ>2 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName>
<settlement type="city">Iowa City</settlement>
<region type="state">Iowa</region>
</placeName>
<orgName type="university">Université de l'Iowa</orgName>
</affiliation>
<affiliation wicri:level="4">
<inist:fA14 i1="05">
<s1>Department of Interdisciplinary Programs in Immunology, University of Iowa</s1>
<s2>Iowa City, Iowa 52242</s2>
<s3>USA</s3>
<sZ>7 aut.</sZ>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName>
<settlement type="city">Iowa City</settlement>
<region type="state">Iowa</region>
</placeName>
<orgName type="university">Université de l'Iowa</orgName>
</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>Infection</term>
<term>Mouse</term>
<term>Severe acute respiratory syndrome</term>
<term>Virology</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr">
<term>Souris</term>
<term>Coronavirus</term>
<term>Virologie</term>
<term>Infection</term>
<term>Syndrome respiratoire aigu sévère</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">The severe acute respiratory syndrome (SARS), caused by a novel coronavirus (SARS-CoV), resulted in substantial morbidity, mortality, and economic losses during the 2003 epidemic. While SARS-CoV infection has not recurred to a significant extent since 2003, it still remains a potential threat. Understanding of SARS and development of therapeutic approaches have been hampered by the absence of an animal model that mimics the human disease and is reproducible. Here we show that transgenic mice that express the SARS-CoV receptor (human angiotensin-converting enzyme 2 [hACE2]) in airway and other epithelia develop a rapidly lethal infection after intranasal inoculation with a human strain of the virus. Infection begins in airway epithelia, with subsequent alveolar involvement and extrapulmonary virus spread to the brain. Infection results in macrophage and lymphocyte infiltration in the lungs and upregulation of proinflammatory cytokines and chemokines in both the lung and the brain. This model of lethal infection with SARS-CoV should be useful for studies of pathogenesis and for the development of antiviral therapies.</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>États-Unis</li>
</country>
<region>
<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="Iowa">
<name sortKey="Mccray, Paul B Jr" sort="Mccray, Paul B Jr" uniqKey="Mccray P" first="Paul B. Jr" last="Mccray">Paul B. Jr Mccray</name>
</region>
<name sortKey="Halabi, Carmen" sort="Halabi, Carmen" uniqKey="Halabi C" first="Carmen" last="Halabi">Carmen Halabi</name>
<name sortKey="Halabi, Carmen" sort="Halabi, Carmen" uniqKey="Halabi C" first="Carmen" last="Halabi">Carmen Halabi</name>
<name sortKey="Hickey, Melissa" sort="Hickey, Melissa" uniqKey="Hickey M" first="Melissa" last="Hickey">Melissa Hickey</name>
<name sortKey="Hong Peng Jia" sort="Hong Peng Jia" uniqKey="Hong Peng Jia" last="Hong Peng Jia">HONG PENG JIA</name>
<name sortKey="Kirby, Patricia" sort="Kirby, Patricia" uniqKey="Kirby P" first="Patricia" last="Kirby">Patricia Kirby</name>
<name sortKey="Lei Shi" sort="Lei Shi" uniqKey="Lei Shi" last="Lei Shi">LEI SHI</name>
<name sortKey="Look, Dwight C" sort="Look, Dwight C" uniqKey="Look D" first="Dwight C." last="Look">Dwight C. Look</name>
<name sortKey="Manzel, Lori" sort="Manzel, Lori" uniqKey="Manzel L" first="Lori" last="Manzel">Lori Manzel</name>
<name sortKey="Mccray, Paul B Jr" sort="Mccray, Paul B Jr" uniqKey="Mccray P" first="Paul B. Jr" last="Mccray">Paul B. Jr Mccray</name>
<name sortKey="Meyerholz, David K" sort="Meyerholz, David K" uniqKey="Meyerholz D" first="David K." last="Meyerholz">David K. Meyerholz</name>
<name sortKey="Netland, Jason" sort="Netland, Jason" uniqKey="Netland J" first="Jason" last="Netland">Jason Netland</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>
<name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name>
<name sortKey="Pewe, Lecia" sort="Pewe, Lecia" uniqKey="Pewe L" first="Lecia" last="Pewe">Lecia Pewe</name>
<name sortKey="Sigmund, Curt D" sort="Sigmund, Curt D" uniqKey="Sigmund C" first="Curt D." last="Sigmund">Curt D. Sigmund</name>
<name sortKey="Sigmund, Curt D" sort="Sigmund, Curt D" uniqKey="Sigmund C" first="Curt D." last="Sigmund">Curt D. Sigmund</name>
<name sortKey="Wohlford Lenane, Christine" sort="Wohlford Lenane, Christine" uniqKey="Wohlford Lenane C" first="Christine" last="Wohlford-Lenane">Christine Wohlford-Lenane</name>
</country>
</tree>
</affiliations>
</record>

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