Severe Acute Respiratory Syndrome Coronavirus Infection of Mice Transgenic for the Human Angiotensin-Converting Enzyme 2 Virus Receptor▿
Identifieur interne : 000708 ( Pmc/Corpus ); précédent : 000707; suivant : 000709Severe Acute Respiratory Syndrome Coronavirus Infection of Mice Transgenic for the Human Angiotensin-Converting Enzyme 2 Virus Receptor▿
Auteurs : Chien-Te K. Tseng ; Cheng Huang ; Patrick Newman ; Nan Wang ; Krishna Narayanan ; Douglas M. Watts ; Shinji Makino ; Michelle M. Packard ; Sherif R. Zaki ; Teh-Sheng Chan ; Clarence J. PetersSource :
- Journal of Virology [ 0022-538X ] ; 2006.
Abstract
Animal models for severe acute respiratory syndrome (SARS) coronavirus infection of humans are needed to elucidate SARS pathogenesis and develop vaccines and antivirals. We developed transgenic mice expressing human angiotensin-converting enzyme 2, a functional receptor for the virus, under the regulation of a global promoter. A transgenic lineage, designated AC70, was among the best characterized against SARS coronavirus infection, showing weight loss and other clinical manifestations before reaching 100% mortality within 8 days after intranasal infection. High virus titers were detected in the lungs and brains of transgene-positive (Tg+) mice on days 1 and 3 after infection. Inflammatory mediators were also detected in these tissues, coinciding with high levels of virus replication. Lower virus titers were also detected in other tissues, including blood. In contrast, infected transgene-negative (Tg−) mice survived without showing any clinical illness. Pathologic examination suggests that the extensive involvement of the central nervous system likely contributed to the death of Tg+ mice, even though viral pneumonia was present. Preliminary studies with mice of a second lineage, AC63, in which the transgene expression was considerably less abundant than that in the AC70 line, revealed that virus replication was largely restricted to the lungs but not the brain. Importantly, despite significant weight loss, infected Tg+ AC63 mice eventually recovered from the illness without any mortality. The severity of the disease that developed in these transgenic mice—AC70 in particular—makes these mouse models valuable not only for evaluating the efficacy of antivirals and vaccines, but also for studying SARS coronavirus pathogenesis.
Url:
DOI: 10.1128/JVI.01702-06
PubMed: 17108019
PubMed Central: 1797529
Links to Exploration step
PMC:1797529Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Severe Acute Respiratory Syndrome Coronavirus Infection of Mice Transgenic for the Human Angiotensin-Converting Enzyme 2 Virus Receptor<xref ref-type="fn" rid="fn1">▿</xref>
</title>
<author><name sortKey="Tseng, Chien Te K" sort="Tseng, Chien Te K" uniqKey="Tseng C" first="Chien-Te K." last="Tseng">Chien-Te K. Tseng</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Huang, Cheng" sort="Huang, Cheng" uniqKey="Huang C" first="Cheng" last="Huang">Cheng Huang</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Newman, Patrick" sort="Newman, Patrick" uniqKey="Newman P" first="Patrick" last="Newman">Patrick Newman</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wang, Nan" sort="Wang, Nan" uniqKey="Wang N" first="Nan" last="Wang">Nan Wang</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Narayanan, Krishna" sort="Narayanan, Krishna" uniqKey="Narayanan K" first="Krishna" last="Narayanan">Krishna Narayanan</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Watts, Douglas M" sort="Watts, Douglas M" uniqKey="Watts D" first="Douglas M." last="Watts">Douglas M. Watts</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Makino, Shinji" sort="Makino, Shinji" uniqKey="Makino S" first="Shinji" last="Makino">Shinji Makino</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Packard, Michelle M" sort="Packard, Michelle M" uniqKey="Packard M" first="Michelle M." last="Packard">Michelle M. Packard</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zaki, Sherif R" sort="Zaki, Sherif R" uniqKey="Zaki S" first="Sherif R." last="Zaki">Sherif R. Zaki</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chan, Teh Sheng" sort="Chan, Teh Sheng" uniqKey="Chan T" first="Teh-Sheng" last="Chan">Teh-Sheng Chan</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Peters, Clarence J" sort="Peters, Clarence J" uniqKey="Peters C" first="Clarence J." last="Peters">Clarence J. Peters</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">17108019</idno>
<idno type="pmc">1797529</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1797529</idno>
<idno type="RBID">PMC:1797529</idno>
<idno type="doi">10.1128/JVI.01702-06</idno>
<date when="2006">2006</date>
<idno type="wicri:Area/Pmc/Corpus">000708</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000708</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Severe Acute Respiratory Syndrome Coronavirus Infection of Mice Transgenic for the Human Angiotensin-Converting Enzyme 2 Virus Receptor<xref ref-type="fn" rid="fn1">▿</xref>
</title>
<author><name sortKey="Tseng, Chien Te K" sort="Tseng, Chien Te K" uniqKey="Tseng C" first="Chien-Te K." last="Tseng">Chien-Te K. Tseng</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Huang, Cheng" sort="Huang, Cheng" uniqKey="Huang C" first="Cheng" last="Huang">Cheng Huang</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Newman, Patrick" sort="Newman, Patrick" uniqKey="Newman P" first="Patrick" last="Newman">Patrick Newman</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wang, Nan" sort="Wang, Nan" uniqKey="Wang N" first="Nan" last="Wang">Nan Wang</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Narayanan, Krishna" sort="Narayanan, Krishna" uniqKey="Narayanan K" first="Krishna" last="Narayanan">Krishna Narayanan</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Watts, Douglas M" sort="Watts, Douglas M" uniqKey="Watts D" first="Douglas M." last="Watts">Douglas M. Watts</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Makino, Shinji" sort="Makino, Shinji" uniqKey="Makino S" first="Shinji" last="Makino">Shinji Makino</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Packard, Michelle M" sort="Packard, Michelle M" uniqKey="Packard M" first="Michelle M." last="Packard">Michelle M. Packard</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zaki, Sherif R" sort="Zaki, Sherif R" uniqKey="Zaki S" first="Sherif R." last="Zaki">Sherif R. Zaki</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chan, Teh Sheng" sort="Chan, Teh Sheng" uniqKey="Chan T" first="Teh-Sheng" last="Chan">Teh-Sheng Chan</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Peters, Clarence J" sort="Peters, Clarence J" uniqKey="Peters C" first="Clarence J." last="Peters">Clarence J. Peters</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<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>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Animal models for severe acute respiratory syndrome (SARS) coronavirus infection of humans are needed to elucidate SARS pathogenesis and develop vaccines and antivirals. We developed transgenic mice expressing human angiotensin-converting enzyme 2, a functional receptor for the virus, under the regulation of a global promoter. A transgenic lineage, designated AC70, was among the best characterized against SARS coronavirus infection, showing weight loss and other clinical manifestations before reaching 100% mortality within 8 days after intranasal infection. High virus titers were detected in the lungs and brains of transgene-positive (Tg<sup>+</sup>
) mice on days 1 and 3 after infection. Inflammatory mediators were also detected in these tissues, coinciding with high levels of virus replication. Lower virus titers were also detected in other tissues, including blood. In contrast, infected transgene-negative (Tg<sup>−</sup>
) mice survived without showing any clinical illness. Pathologic examination suggests that the extensive involvement of the central nervous system likely contributed to the death of Tg<sup>+</sup>
mice, even though viral pneumonia was present. Preliminary studies with mice of a second lineage, AC63, in which the transgene expression was considerably less abundant than that in the AC70 line, revealed that virus replication was largely restricted to the lungs but not the brain. Importantly, despite significant weight loss, infected Tg<sup>+</sup>
AC63 mice eventually recovered from the illness without any mortality. The severity of the disease that developed in these transgenic mice—AC70 in particular—makes these mouse models valuable not only for evaluating the efficacy of antivirals and vaccines, but also for studying SARS coronavirus pathogenesis.</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">17108019</article-id>
<article-id pub-id-type="pmc">1797529</article-id>
<article-id pub-id-type="publisher-id">1702-06</article-id>
<article-id pub-id-type="doi">10.1128/JVI.01702-06</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Pathogenesis and Immunity</subject>
</subj-group>
</article-categories>
<title-group><article-title>Severe Acute Respiratory Syndrome Coronavirus Infection of Mice Transgenic for the Human Angiotensin-Converting Enzyme 2 Virus Receptor<xref ref-type="fn" rid="fn1">▿</xref>
</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Tseng</surname>
<given-names>Chien-Te K.</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="aff" rid="aff1">3</xref>
<xref ref-type="corresp" rid="cor1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Huang</surname>
<given-names>Cheng</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Newman</surname>
<given-names>Patrick</given-names>
</name>
<xref ref-type="aff" rid="aff1">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wang</surname>
<given-names>Nan</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Narayanan</surname>
<given-names>Krishna</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Watts</surname>
<given-names>Douglas M.</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>Makino</surname>
<given-names>Shinji</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="aff" rid="aff1">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Packard</surname>
<given-names>Michelle M.</given-names>
</name>
<xref ref-type="aff" rid="aff1">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zaki</surname>
<given-names>Sherif R.</given-names>
</name>
<xref ref-type="aff" rid="aff1">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chan</surname>
<given-names>Teh-sheng</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Peters</surname>
<given-names>Clarence J.</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="aff" rid="aff1">2</xref>
<xref ref-type="aff" rid="aff1">3</xref>
</contrib>
</contrib-group>
<aff id="aff1">Departments of Microbiology and Immunology,<label>1</label>
Pathology,<label>2</label>
Center of Biodefense and Emerging Infectious Disease, University of Texas Medical Branch, Galveston, Texas,<label>3</label>
Centers for Disease Control and Prevention, Atlanta, Georgia<label>4</label>
</aff>
<author-notes><fn id="cor1"><label>*</label>
<p>Corresponding author. Mailing address: Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Boulevard, G-150 Keiller Building, Galveston, TX 77555-0609. Phone: (409) 772-0175. Fax: (409) 747-0762. E-mail: <email>sktseng@utmb.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>1162</fpage>
<lpage>1173</lpage>
<history><date date-type="received"><day>7</day>
<month>8</month>
<year>2006</year>
</date>
<date date-type="accepted"><day>10</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="zjv00307001162.pdf"></self-uri>
<abstract><p>Animal models for severe acute respiratory syndrome (SARS) coronavirus infection of humans are needed to elucidate SARS pathogenesis and develop vaccines and antivirals. We developed transgenic mice expressing human angiotensin-converting enzyme 2, a functional receptor for the virus, under the regulation of a global promoter. A transgenic lineage, designated AC70, was among the best characterized against SARS coronavirus infection, showing weight loss and other clinical manifestations before reaching 100% mortality within 8 days after intranasal infection. High virus titers were detected in the lungs and brains of transgene-positive (Tg<sup>+</sup>
) mice on days 1 and 3 after infection. Inflammatory mediators were also detected in these tissues, coinciding with high levels of virus replication. Lower virus titers were also detected in other tissues, including blood. In contrast, infected transgene-negative (Tg<sup>−</sup>
) mice survived without showing any clinical illness. Pathologic examination suggests that the extensive involvement of the central nervous system likely contributed to the death of Tg<sup>+</sup>
mice, even though viral pneumonia was present. Preliminary studies with mice of a second lineage, AC63, in which the transgene expression was considerably less abundant than that in the AC70 line, revealed that virus replication was largely restricted to the lungs but not the brain. Importantly, despite significant weight loss, infected Tg<sup>+</sup>
AC63 mice eventually recovered from the illness without any mortality. The severity of the disease that developed in these transgenic mice—AC70 in particular—makes these mouse models valuable not only for evaluating the efficacy of antivirals and vaccines, but also for studying SARS coronavirus pathogenesis.</p>
</abstract>
</article-meta>
</front>
</pmc>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000708 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 000708 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Sante |area= SrasV1 |flux= Pmc |étape= Corpus |type= RBID |clé= PMC:1797529 |texte= Severe Acute Respiratory Syndrome Coronavirus Infection of Mice Transgenic for the Human Angiotensin-Converting Enzyme 2 Virus Receptor▿ }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/RBID.i -Sk "pubmed:17108019" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd \ | NlmPubMed2Wicri -a SrasV1
![]() | This area was generated with Dilib version V0.6.33. | ![]() |