Differential Virological and Immunological Outcome of Severe Acute Respiratory Syndrome Coronavirus Infection in Susceptible and Resistant Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2
Identifieur interne : 002F35 ( Main/Curation ); précédent : 002F34; suivant : 002F36Differential Virological and Immunological Outcome of Severe Acute Respiratory Syndrome Coronavirus Infection in Susceptible and Resistant Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2
Auteurs : Naoko Yoshikawa [États-Unis] ; Tomoki Yoshikawa [États-Unis] ; Terence Hill [États-Unis] ; CHENG HUANG [États-Unis] ; Douglas M. Watts [États-Unis] ; Shinji Makino [États-Unis] ; Gregg Milligan [États-Unis] ; Tehsheng Chan [États-Unis] ; Clarence J. Peter [États-Unis] ; Chien-Te K. Tseng [États-Unis]Source :
- Journal of virology [ 0022-538X ] ; 2009.
Descripteurs français
- KwdFr :
- Animaux, Cinétique, Concanavaline A (pharmacologie), Cytokines (immunologie), Encéphalopathies (virologie), Humains, Lymphocytes (), Lymphocytes (cytologie), Lymphocytes (immunologie), Maladies pulmonaires (virologie), Peptidyl-Dipeptidase A (génétique), Peptidyl-Dipeptidase A (métabolisme), Prolifération cellulaire (), Prédisposition génétique à une maladie (génétique), Rate (), Rate (cytologie), Rate (immunologie), Régulation de l'expression des gènes codant pour des enzymes, Réplication virale, Souris, Souris transgéniques, Spécificité d'organe, Syndrome respiratoire aigu sévère (anatomopathologie), Syndrome respiratoire aigu sévère (immunologie), Syndrome respiratoire aigu sévère (métabolisme), Syndrome respiratoire aigu sévère (virologie), Virus du SRAS (immunologie).
- MESH :
- anatomopathologie : Syndrome respiratoire aigu sévère.
- cytologie : Lymphocytes, Rate.
- génétique : Peptidyl-Dipeptidase A, Prédisposition génétique à une maladie.
- immunologie : Cytokines, Lymphocytes, Rate, Syndrome respiratoire aigu sévère, Virus du SRAS.
- métabolisme : Peptidyl-Dipeptidase A, Syndrome respiratoire aigu sévère.
- pharmacologie : Concanavaline A.
- virologie : Encéphalopathies, Maladies pulmonaires, Syndrome respiratoire aigu sévère.
- Pascal (Inist)
- Animaux, Cinétique, Coronavirus, Animal transgénique, Humains, Lymphocytes, Prolifération cellulaire, Rate, Régulation de l'expression des gènes codant pour des enzymes, Réplication virale, Souris, Homme, Pronostic, Infection, Résistance, Souris transgéniques, Spécificité d'organe, Virologie, Syndrome respiratoire aigu sévère, Angiotensin converting enzyme 2.
- Wicri :
- topic : Animal transgénique, Homme.
English descriptors
- KwdEn :
- Animals, Brain Diseases (virology), Cell Proliferation (drug effects), Concanavalin A (pharmacology), Coronavirus, Cytokines (immunology), Gene Expression Regulation, Enzymologic, Genetic Predisposition to Disease (genetics), Human, Humans, Infection, Kinetics, Lung Diseases (virology), Lymphocytes (cytology), Lymphocytes (drug effects), Lymphocytes (immunology), Mice, Mice, Transgenic, Mouse, Organ Specificity, Peptidyl-Dipeptidase A (genetics), Peptidyl-Dipeptidase A (metabolism), Prognosis, Resistance, SARS Virus (immunology), Severe Acute Respiratory Syndrome (immunology), Severe Acute Respiratory Syndrome (metabolism), Severe Acute Respiratory Syndrome (pathology), Severe Acute Respiratory Syndrome (virology), Severe acute respiratory syndrome, Spleen (cytology), Spleen (drug effects), Spleen (immunology), Transgenic animal, Virology, Virus Replication.
- MESH :
- chemical , genetics : Peptidyl-Dipeptidase A.
- chemical , immunology : Cytokines.
- chemical , metabolism : Peptidyl-Dipeptidase A.
- chemical , pharmacology : Concanavalin A.
- cytology : Lymphocytes, Spleen.
- drug effects : Cell Proliferation, Lymphocytes, Spleen.
- genetics : Genetic Predisposition to Disease.
- immunology : Lymphocytes, SARS Virus, Severe Acute Respiratory Syndrome, Spleen.
- metabolism : Severe Acute Respiratory Syndrome.
- pathology : Severe Acute Respiratory Syndrome.
- virology : Brain Diseases, Lung Diseases, Severe Acute Respiratory Syndrome.
- Animals, Gene Expression Regulation, Enzymologic, Humans, Kinetics, Mice, Mice, Transgenic, Organ Specificity, Virus Replication.
Abstract
We previously reported that transgenic (Tg) mice expressing human angiotensin-converting enzyme 2 (hACE2), the receptor for severe acute respiratory syndrome coronavirus (SARS-CoV), were highly susceptible to SARS-CoV infection, which resulted in the development of disease of various severity and even death in some lineages. In this study, we further characterized and compared the pathogeneses of SARS-CoV infection in two of the most stable Tg lineages, AC70 and AC22, representing those susceptible and resistant to the lethal SARS-CoV infection, respectively. The kinetics of virus replication and the inflammatory responses within the lungs and brains, as well as the clinical and pathological outcomes, were assessed in each lineage. In addition, we generated information on lymphocyte subsets and mitogen-mediated proliferation of splenocytes. We found that while both lineages were permissive to SARS-CoV infection, causing elevated secretion of many inflammatory mediators within the lungs and brains, viral infection appeared to be more intense in AC70 than in AC22 mice, especially in the brain. Moreover, such infection was accompanied by a more profound immune suppression in the former, as evidenced by the extensive loss ofT cells, compromised responses to concanavalin A stimulation, and absence of inflammatory infiltrates within the brain. We also found that CD8+ T cells were partially effective in attenuating the pathogenesis of SARS-CoV infection in lethality-resistant AC22 mice. Collectively, our data revealed a more intense viral infection and immunosuppression in AC70 mice than in AC22 mice, thereby providing us with an immunopathogenic basis for the fatal outcome of SARS-CoV infection in the AC70 mice.
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Pascal:09-0239898Le document en format XML
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<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="2009">2009</date>
</imprint>
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<seriesStmt><title level="j" type="main">Journal of virology</title>
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<term>Brain Diseases (virology)</term>
<term>Cell Proliferation (drug effects)</term>
<term>Concanavalin A (pharmacology)</term>
<term>Coronavirus</term>
<term>Cytokines (immunology)</term>
<term>Gene Expression Regulation, Enzymologic</term>
<term>Genetic Predisposition to Disease (genetics)</term>
<term>Human</term>
<term>Humans</term>
<term>Infection</term>
<term>Kinetics</term>
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<term>Lymphocytes (immunology)</term>
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<term>Mouse</term>
<term>Organ Specificity</term>
<term>Peptidyl-Dipeptidase A (genetics)</term>
<term>Peptidyl-Dipeptidase A (metabolism)</term>
<term>Prognosis</term>
<term>Resistance</term>
<term>SARS Virus (immunology)</term>
<term>Severe Acute Respiratory Syndrome (immunology)</term>
<term>Severe Acute Respiratory Syndrome (metabolism)</term>
<term>Severe Acute Respiratory Syndrome (pathology)</term>
<term>Severe Acute Respiratory Syndrome (virology)</term>
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<term>Lung Diseases</term>
<term>Severe Acute Respiratory Syndrome</term>
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<term>Gene Expression Regulation, Enzymologic</term>
<term>Humans</term>
<term>Kinetics</term>
<term>Mice</term>
<term>Mice, Transgenic</term>
<term>Organ Specificity</term>
<term>Virus Replication</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Animaux</term>
<term>Cinétique</term>
<term>Coronavirus</term>
<term>Animal transgénique</term>
<term>Humains</term>
<term>Lymphocytes</term>
<term>Prolifération cellulaire</term>
<term>Rate</term>
<term>Régulation de l'expression des gènes codant pour des enzymes</term>
<term>Réplication virale</term>
<term>Souris</term>
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<term>Pronostic</term>
<term>Infection</term>
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<term>Spécificité d'organe</term>
<term>Virologie</term>
<term>Syndrome respiratoire aigu sévère</term>
<term>Angiotensin converting enzyme 2</term>
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<front><div type="abstract" xml:lang="en">We previously reported that transgenic (Tg) mice expressing human angiotensin-converting enzyme 2 (hACE2), the receptor for severe acute respiratory syndrome coronavirus (SARS-CoV), were highly susceptible to SARS-CoV infection, which resulted in the development of disease of various severity and even death in some lineages. In this study, we further characterized and compared the pathogeneses of SARS-CoV infection in two of the most stable Tg lineages, AC70 and AC22, representing those susceptible and resistant to the lethal SARS-CoV infection, respectively. The kinetics of virus replication and the inflammatory responses within the lungs and brains, as well as the clinical and pathological outcomes, were assessed in each lineage. In addition, we generated information on lymphocyte subsets and mitogen-mediated proliferation of splenocytes. We found that while both lineages were permissive to SARS-CoV infection, causing elevated secretion of many inflammatory mediators within the lungs and brains, viral infection appeared to be more intense in AC70 than in AC22 mice, especially in the brain. Moreover, such infection was accompanied by a more profound immune suppression in the former, as evidenced by the extensive loss ofT cells, compromised responses to concanavalin A stimulation, and absence of inflammatory infiltrates within the brain. We also found that CD8<sup>+</sup>
T cells were partially effective in attenuating the pathogenesis of SARS-CoV infection in lethality-resistant AC22 mice. Collectively, our data revealed a more intense viral infection and immunosuppression in AC70 mice than in AC22 mice, thereby providing us with an immunopathogenic basis for the fatal outcome of SARS-CoV infection in the AC70 mice.</div>
</front>
</TEI>
<double idat="0022-538X:2009:Yoshikawa N:differential:virological:and"><INIST><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">Differential Virological and Immunological Outcome of Severe Acute Respiratory Syndrome Coronavirus Infection in Susceptible and Resistant Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2</title>
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<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Microbiology and Immunology, University of Texas Medical Branch</s1>
<s2>Galveston, Texas 77555-0609</s2>
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</affiliation>
</author>
<author><name sortKey="Yoshikawa, Tomoki" sort="Yoshikawa, Tomoki" uniqKey="Yoshikawa T" first="Tomoki" last="Yoshikawa">Tomoki Yoshikawa</name>
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<author><name sortKey="Cheng Huang" sort="Cheng Huang" uniqKey="Cheng Huang" last="Cheng Huang">CHENG HUANG</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Differential Virological and Immunological Outcome of Severe Acute Respiratory Syndrome Coronavirus Infection in Susceptible and Resistant Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2</title>
<author><name sortKey="Yoshikawa, Naoko" sort="Yoshikawa, Naoko" uniqKey="Yoshikawa N" first="Naoko" last="Yoshikawa">Naoko Yoshikawa</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Microbiology and Immunology, University of Texas Medical Branch</s1>
<s2>Galveston, Texas 77555-0609</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
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</inist:fA14>
<country>États-Unis</country>
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</affiliation>
</author>
<author><name sortKey="Yoshikawa, Tomoki" sort="Yoshikawa, Tomoki" uniqKey="Yoshikawa T" first="Tomoki" last="Yoshikawa">Tomoki Yoshikawa</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Microbiology and Immunology, University of Texas Medical Branch</s1>
<s2>Galveston, Texas 77555-0609</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Galveston, Texas 77555-0609</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Hill, Terence" sort="Hill, Terence" uniqKey="Hill T" first="Terence" last="Hill">Terence Hill</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Microbiology and Immunology, University of Texas Medical Branch</s1>
<s2>Galveston, Texas 77555-0609</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Galveston, Texas 77555-0609</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Cheng Huang" sort="Cheng Huang" uniqKey="Cheng Huang" last="Cheng Huang">CHENG HUANG</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Microbiology and Immunology, University of Texas Medical Branch</s1>
<s2>Galveston, Texas 77555-0609</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Galveston, Texas 77555-0609</wicri:noRegion>
</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 wicri:level="1"><inist:fA14 i1="02"><s1>Department of Pathology, University of Texas Medical Branch</s1>
<s2>Galveston, Texas 77555-0609</s2>
<s3>USA</s3>
<sZ>5 aut.</sZ>
<sZ>9 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Galveston, Texas 77555-0609</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Makino, Shinji" sort="Makino, Shinji" uniqKey="Makino S" first="Shinji" last="Makino">Shinji Makino</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Microbiology and Immunology, University of Texas Medical Branch</s1>
<s2>Galveston, Texas 77555-0609</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Galveston, Texas 77555-0609</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Milligan, Gregg" sort="Milligan, Gregg" uniqKey="Milligan G" first="Gregg" last="Milligan">Gregg Milligan</name>
<affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Pediatrics, University of Texas Medical Branch</s1>
<s2>Galveston, Texas 77555-0609</s2>
<s3>USA</s3>
<sZ>7 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Galveston, Texas 77555-0609</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Chan, Tehsheng" sort="Chan, Tehsheng" uniqKey="Chan T" first="Tehsheng" last="Chan">Tehsheng Chan</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Microbiology and Immunology, University of Texas Medical Branch</s1>
<s2>Galveston, Texas 77555-0609</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Galveston, Texas 77555-0609</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Peter, Clarence J" sort="Peter, Clarence J" uniqKey="Peter C" first="Clarence J." last="Peter">Clarence J. Peter</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Microbiology and Immunology, University of Texas Medical Branch</s1>
<s2>Galveston, Texas 77555-0609</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Galveston, Texas 77555-0609</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Pathology, University of Texas Medical Branch</s1>
<s2>Galveston, Texas 77555-0609</s2>
<s3>USA</s3>
<sZ>5 aut.</sZ>
<sZ>9 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Galveston, Texas 77555-0609</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Center for Biodefense and Emerging Infectious Disease, University of Texas Medical Branch</s1>
<s2>Galveston, Texas 77555-0609</s2>
<s3>USA</s3>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Galveston, Texas 77555-0609</wicri:noRegion>
</affiliation>
</author>
<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 wicri:level="1"><inist:fA14 i1="01"><s1>Department of Microbiology and Immunology, University of Texas Medical Branch</s1>
<s2>Galveston, Texas 77555-0609</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Galveston, Texas 77555-0609</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Center for Biodefense and Emerging Infectious Disease, University of Texas Medical Branch</s1>
<s2>Galveston, Texas 77555-0609</s2>
<s3>USA</s3>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Galveston, Texas 77555-0609</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="2009">2009</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>Human</term>
<term>Infection</term>
<term>Mouse</term>
<term>Prognosis</term>
<term>Resistance</term>
<term>Severe acute respiratory syndrome</term>
<term>Transgenic animal</term>
<term>Virology</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Coronavirus</term>
<term>Animal transgénique</term>
<term>Souris</term>
<term>Homme</term>
<term>Pronostic</term>
<term>Infection</term>
<term>Résistance</term>
<term>Virologie</term>
<term>Syndrome respiratoire aigu sévère</term>
<term>Angiotensin converting enzyme 2</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Animal transgénique</term>
<term>Homme</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">We previously reported that transgenic (Tg) mice expressing human angiotensin-converting enzyme 2 (hACE2), the receptor for severe acute respiratory syndrome coronavirus (SARS-CoV), were highly susceptible to SARS-CoV infection, which resulted in the development of disease of various severity and even death in some lineages. In this study, we further characterized and compared the pathogeneses of SARS-CoV infection in two of the most stable Tg lineages, AC70 and AC22, representing those susceptible and resistant to the lethal SARS-CoV infection, respectively. The kinetics of virus replication and the inflammatory responses within the lungs and brains, as well as the clinical and pathological outcomes, were assessed in each lineage. In addition, we generated information on lymphocyte subsets and mitogen-mediated proliferation of splenocytes. We found that while both lineages were permissive to SARS-CoV infection, causing elevated secretion of many inflammatory mediators within the lungs and brains, viral infection appeared to be more intense in AC70 than in AC22 mice, especially in the brain. Moreover, such infection was accompanied by a more profound immune suppression in the former, as evidenced by the extensive loss ofT cells, compromised responses to concanavalin A stimulation, and absence of inflammatory infiltrates within the brain. We also found that CD8<sup>+</sup>
T cells were partially effective in attenuating the pathogenesis of SARS-CoV infection in lethality-resistant AC22 mice. Collectively, our data revealed a more intense viral infection and immunosuppression in AC70 mice than in AC22 mice, thereby providing us with an immunopathogenic basis for the fatal outcome of SARS-CoV infection in the AC70 mice.</div>
</front>
</TEI>
</INIST>
<PMC><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Differential Virological and Immunological Outcome of Severe Acute Respiratory Syndrome Coronavirus Infection in Susceptible and Resistant Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2<xref ref-type="fn" rid="fn1">▿</xref>
</title>
<author><name sortKey="Yoshikawa, Naoko" sort="Yoshikawa, Naoko" uniqKey="Yoshikawa N" first="Naoko" last="Yoshikawa">Naoko Yoshikawa</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Yoshikawa, Tomoki" sort="Yoshikawa, Tomoki" uniqKey="Yoshikawa T" first="Tomoki" last="Yoshikawa">Tomoki Yoshikawa</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hill, Terence" sort="Hill, Terence" uniqKey="Hill T" first="Terence" last="Hill">Terence Hill</name>
<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="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>
</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>
</author>
<author><name sortKey="Milligan, Gregg" sort="Milligan, Gregg" uniqKey="Milligan G" first="Gregg" last="Milligan">Gregg Milligan</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chan, Tehsheng" sort="Chan, Tehsheng" uniqKey="Chan T" first="Tehsheng" last="Chan">Tehsheng 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>
<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>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">19297479</idno>
<idno type="pmc">2681954</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2681954</idno>
<idno type="RBID">PMC:2681954</idno>
<idno type="doi">10.1128/JVI.02272-08</idno>
<date when="2009">2009</date>
<idno type="wicri:Area/Pmc/Corpus">000671</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000671</idno>
<idno type="wicri:Area/Pmc/Curation">000671</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000671</idno>
<idno type="wicri:Area/Pmc/Checkpoint">000D32</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000D32</idno>
<idno type="wicri:source">PubMed</idno>
<idno type="RBID">pubmed:19297479</idno>
<idno type="wicri:Area/PubMed/Corpus">001941</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001941</idno>
<idno type="wicri:Area/PubMed/Curation">001941</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001941</idno>
<idno type="wicri:Area/PubMed/Checkpoint">001895</idno>
<idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001895</idno>
<idno type="wicri:Area/Ncbi/Merge">001E74</idno>
<idno type="wicri:Area/Ncbi/Curation">001E74</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">001E74</idno>
<idno type="wicri:doubleKey">0022-538X:2009:Yoshikawa N:differential:virological:and</idno>
<idno type="wicri:Area/Main/Merge">002B90</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Differential Virological and Immunological Outcome of Severe Acute Respiratory Syndrome Coronavirus Infection in Susceptible and Resistant Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2<xref ref-type="fn" rid="fn1">▿</xref>
</title>
<author><name sortKey="Yoshikawa, Naoko" sort="Yoshikawa, Naoko" uniqKey="Yoshikawa N" first="Naoko" last="Yoshikawa">Naoko Yoshikawa</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Yoshikawa, Tomoki" sort="Yoshikawa, Tomoki" uniqKey="Yoshikawa T" first="Tomoki" last="Yoshikawa">Tomoki Yoshikawa</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hill, Terence" sort="Hill, Terence" uniqKey="Hill T" first="Terence" last="Hill">Terence Hill</name>
<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="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>
</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>
</author>
<author><name sortKey="Milligan, Gregg" sort="Milligan, Gregg" uniqKey="Milligan G" first="Gregg" last="Milligan">Gregg Milligan</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chan, Tehsheng" sort="Chan, Tehsheng" uniqKey="Chan T" first="Tehsheng" last="Chan">Tehsheng 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>
<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>
</analytic>
<series><title level="j">Journal of Virology</title>
<idno type="ISSN">0022-538X</idno>
<idno type="eISSN">1098-5514</idno>
<imprint><date when="2009">2009</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term>
<term>Brain Diseases (virology)</term>
<term>Cell Proliferation (drug effects)</term>
<term>Concanavalin A (pharmacology)</term>
<term>Cytokines (immunology)</term>
<term>Gene Expression Regulation, Enzymologic</term>
<term>Genetic Predisposition to Disease (genetics)</term>
<term>Humans</term>
<term>Kinetics</term>
<term>Lung Diseases (virology)</term>
<term>Lymphocytes (cytology)</term>
<term>Lymphocytes (drug effects)</term>
<term>Lymphocytes (immunology)</term>
<term>Mice</term>
<term>Mice, Transgenic</term>
<term>Organ Specificity</term>
<term>Peptidyl-Dipeptidase A (genetics)</term>
<term>Peptidyl-Dipeptidase A (metabolism)</term>
<term>SARS Virus (immunology)</term>
<term>Severe Acute Respiratory Syndrome (immunology)</term>
<term>Severe Acute Respiratory Syndrome (metabolism)</term>
<term>Severe Acute Respiratory Syndrome (pathology)</term>
<term>Severe Acute Respiratory Syndrome (virology)</term>
<term>Spleen (cytology)</term>
<term>Spleen (drug effects)</term>
<term>Spleen (immunology)</term>
<term>Virus Replication</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term>
<term>Cinétique</term>
<term>Concanavaline A (pharmacologie)</term>
<term>Cytokines (immunologie)</term>
<term>Encéphalopathies (virologie)</term>
<term>Humains</term>
<term>Lymphocytes ()</term>
<term>Lymphocytes (cytologie)</term>
<term>Lymphocytes (immunologie)</term>
<term>Maladies pulmonaires (virologie)</term>
<term>Peptidyl-Dipeptidase A (génétique)</term>
<term>Peptidyl-Dipeptidase A (métabolisme)</term>
<term>Prolifération cellulaire ()</term>
<term>Prédisposition génétique à une maladie (génétique)</term>
<term>Rate ()</term>
<term>Rate (cytologie)</term>
<term>Rate (immunologie)</term>
<term>Régulation de l'expression des gènes codant pour des enzymes</term>
<term>Réplication virale</term>
<term>Souris</term>
<term>Souris transgéniques</term>
<term>Spécificité d'organe</term>
<term>Syndrome respiratoire aigu sévère (anatomopathologie)</term>
<term>Syndrome respiratoire aigu sévère (immunologie)</term>
<term>Syndrome respiratoire aigu sévère (métabolisme)</term>
<term>Syndrome respiratoire aigu sévère (virologie)</term>
<term>Virus du SRAS (immunologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Peptidyl-Dipeptidase A</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Cytokines</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Peptidyl-Dipeptidase A</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Concanavalin A</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Syndrome respiratoire aigu sévère</term>
</keywords>
<keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Lymphocytes</term>
<term>Rate</term>
</keywords>
<keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Lymphocytes</term>
<term>Spleen</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cell Proliferation</term>
<term>Lymphocytes</term>
<term>Spleen</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Genetic Predisposition to Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Peptidyl-Dipeptidase A</term>
<term>Prédisposition génétique à une maladie</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Cytokines</term>
<term>Lymphocytes</term>
<term>Rate</term>
<term>Syndrome respiratoire aigu sévère</term>
<term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Lymphocytes</term>
<term>SARS Virus</term>
<term>Severe Acute Respiratory Syndrome</term>
<term>Spleen</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Peptidyl-Dipeptidase A</term>
<term>Syndrome respiratoire aigu sévère</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Concanavaline A</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Encéphalopathies</term>
<term>Maladies pulmonaires</term>
<term>Syndrome respiratoire aigu sévère</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Brain Diseases</term>
<term>Lung Diseases</term>
<term>Severe Acute Respiratory Syndrome</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Gene Expression Regulation, Enzymologic</term>
<term>Humans</term>
<term>Kinetics</term>
<term>Mice</term>
<term>Mice, Transgenic</term>
<term>Organ Specificity</term>
<term>Virus Replication</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Cinétique</term>
<term>Humains</term>
<term>Lymphocytes</term>
<term>Prolifération cellulaire</term>
<term>Rate</term>
<term>Régulation de l'expression des gènes codant pour des enzymes</term>
<term>Réplication virale</term>
<term>Souris</term>
<term>Souris transgéniques</term>
<term>Spécificité d'organe</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>We previously reported that transgenic (Tg) mice expressing human angiotensin-converting enzyme 2 (hACE2), the receptor for severe acute respiratory syndrome coronavirus (SARS-CoV), were highly susceptible to SARS-CoV infection, which resulted in the development of disease of various severity and even death in some lineages. In this study, we further characterized and compared the pathogeneses of SARS-CoV infection in two of the most stable Tg lineages, AC70 and AC22, representing those susceptible and resistant to the lethal SARS-CoV infection, respectively. The kinetics of virus replication and the inflammatory responses within the lungs and brains, as well as the clinical and pathological outcomes, were assessed in each lineage. In addition, we generated information on lymphocyte subsets and mitogen-mediated proliferation of splenocytes. We found that while both lineages were permissive to SARS-CoV infection, causing elevated secretion of many inflammatory mediators within the lungs and brains, viral infection appeared to be more intense in AC70 than in AC22 mice, especially in the brain. Moreover, such infection was accompanied by a more profound immune suppression in the former, as evidenced by the extensive loss of T cells, compromised responses to concanavalin A stimulation, and absence of inflammatory infiltrates within the brain. We also found that CD8<sup>+</sup>
T cells were partially effective in attenuating the pathogenesis of SARS-CoV infection in lethality-resistant AC22 mice. Collectively, our data revealed a more intense viral infection and immunosuppression in AC70 mice than in AC22 mice, thereby providing us with an immunopathogenic basis for the fatal outcome of SARS-CoV infection in the AC70 mice.</p>
</div>
</front>
</TEI>
</PMC>
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