Intranasal Treatment with Poly(I.C) Protects Aged Mice from Lethal Respiratory Virus Infections
Identifieur interne : 001F78 ( Main/Exploration ); précédent : 001F77; suivant : 001F79Intranasal Treatment with Poly(I.C) Protects Aged Mice from Lethal Respiratory Virus Infections
Auteurs : JINCUN ZHAO [États-Unis] ; Christine Wohlford-Lenane [États-Unis] ; JINGXIAN ZHAO [États-Unis, République populaire de Chine] ; Erica Fleming [États-Unis] ; Thomas E. Lane [États-Unis] ; Paul B. Jr Mccray [États-Unis] ; Stanley Perlman [États-Unis]Source :
- Journal of virology [ 0022-538X ] ; 2012.
Descripteurs français
- Pascal (Inist)
English descriptors
Abstract
In the 2002-2003 severe acute respiratory syndrome coronavirus (SARS-CoV) epidemic, no patients under 24 years of age died, while mortality was greater than 50% in those over 65 years. Greater than 90% of all deaths from influenza A virus (IAV) occur in the elderly (> 65 years of age). To address this age-related susceptibility to SARS-CoV and IAV, we infected C57BL/6 (B6) mice with mouse-adapted SARS-CoV (MA15) or IAV (PR8), both of which cause severe disease in aged mice. Intranasal pretreatment of aged mice with poly(I.C) (a TLR3 agonist) and, to a lesser extent, CpG, R848, or lipopolysaccharide (TLR9, TLR7/8, or TLR4 agonists), provided a high level of protection [90% to 100% survival rate after poly(I.C) treatment] against lethal MA15 or IAV challenge and reduced pathological changes and virus loads in the lungs at early times after infection. Poly(I.C) pretreatment upregulated beta interferon (IFN-β), IFN-γ, IL-1β, and tumor necrosis factor (TNF) gene expression in the lungs. Intranasal pretreatment with IFN-β or IFN-γ but not IL-1β or TNF also protected aged mice, consistent with the notion that poly(I.C) pretreatment functioned, at least in part, by inducing IFN-β and IFN-γ. We also identified a potential cellular target for poly(I.C) by showing that treatment inhibited virus replication in primary human airway epithelial cells. These results suggest that intranasal poly(I.C) should be evaluated as a prophylactic agent in aged individuals at high risk for contracting SARS-CoV or IAV infections.
Affiliations:
- République populaire de Chine, États-Unis
- Californie, Guangdong, Iowa
- Iowa City, Jiangmen
- Université de l'Iowa
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Iowa</s1><s2>Iowa City, Iowa</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation></author><author><name sortKey="Wohlford Lenane, Christine" sort="Wohlford Lenane, Christine" uniqKey="Wohlford Lenane C" first="Christine" last="Wohlford-Lenane">Christine Wohlford-Lenane</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Department of Pediatrics, University of Iowa</s1><s2>Iowa City, Iowa</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation></author><author><name sortKey="Jingxian Zhao" sort="Jingxian Zhao" 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Fleming</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Department of Microbiology, University of Iowa</s1><s2>Iowa City, Iowa</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation></author><author><name sortKey="Lane, Thomas E" sort="Lane, Thomas E" uniqKey="Lane T" first="Thomas E." last="Lane">Thomas E. Lane</name><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Department of Molecular Biology and Biochemistry, University of California at Irvine</s1><s2>Irvine, California</s2><s3>USA</s3><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Californie</region></placeName></affiliation></author><author><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><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Department of Microbiology, University of Iowa</s1><s2>Iowa City, Iowa</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Department of Pediatrics, University of Iowa</s1><s2>Iowa City, Iowa</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></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 Microbiology, University of Iowa</s1><s2>Iowa City, Iowa</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Department of Pediatrics, University of Iowa</s1><s2>Iowa City, Iowa</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></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="2012">2012</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>Intranasal administration</term><term>Mouse</term><term>Respiratory disease</term><term>Treatment</term><term>Viral disease</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Souris</term><term>Voie intranasale</term><term>Traitement</term><term>Pathologie de l'appareil respiratoire</term><term>Virose</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">In the 2002-2003 severe acute respiratory syndrome coronavirus (SARS-CoV) epidemic, no patients under 24 years of age died, while mortality was greater than 50% in those over 65 years. Greater than 90% of all deaths from influenza A virus (IAV) occur in the elderly (> 65 years of age). To address this age-related susceptibility to SARS-CoV and IAV, we infected C57BL/6 (B6) mice with mouse-adapted SARS-CoV (MA15) or IAV (PR8), both of which cause severe disease in aged mice. Intranasal pretreatment of aged mice with poly(I.C) (a TLR3 agonist) and, to a lesser extent, CpG, R848, or lipopolysaccharide (TLR9, TLR7/8, or TLR4 agonists), provided a high level of protection [90% to 100% survival rate after poly(I.C) treatment] against lethal MA15 or IAV challenge and reduced pathological changes and virus loads in the lungs at early times after infection. Poly(I.C) pretreatment upregulated beta interferon (IFN-β), IFN-γ, IL-1β, and tumor necrosis factor (TNF) gene expression in the lungs. Intranasal pretreatment with IFN-β or IFN-γ but not IL-1β or TNF also protected aged mice, consistent with the notion that poly(I.C) pretreatment functioned, at least in part, by inducing IFN-β and IFN-γ. We also identified a potential cellular target for poly(I.C) by showing that treatment inhibited virus replication in primary human airway epithelial cells. These results suggest that intranasal poly(I.C) should be evaluated as a prophylactic agent in aged individuals at high risk for contracting SARS-CoV or IAV infections.</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li><li>États-Unis</li></country><region><li>Californie</li><li>Guangdong</li><li>Iowa</li></region><settlement><li>Iowa City</li><li>Jiangmen</li></settlement><orgName><li>Université de l'Iowa</li></orgName></list><tree><country name="États-Unis"><region name="Iowa"><name sortKey="Jincun Zhao" sort="Jincun Zhao" uniqKey="Jincun Zhao" last="Jincun Zhao">JINCUN ZHAO</name></region><name sortKey="Fleming, Erica" sort="Fleming, Erica" uniqKey="Fleming E" first="Erica" last="Fleming">Erica Fleming</name><name sortKey="Jingxian Zhao" sort="Jingxian Zhao" uniqKey="Jingxian Zhao" last="Jingxian Zhao">JINGXIAN ZHAO</name><name sortKey="Lane, Thomas E" sort="Lane, Thomas E" uniqKey="Lane T" first="Thomas E." last="Lane">Thomas E. Lane</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="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="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="Wohlford Lenane, Christine" sort="Wohlford Lenane, Christine" uniqKey="Wohlford Lenane C" first="Christine" last="Wohlford-Lenane">Christine Wohlford-Lenane</name></country><country name="République populaire de Chine"><region name="Guangdong"><name sortKey="Jingxian Zhao" sort="Jingxian Zhao" uniqKey="Jingxian Zhao" last="Jingxian Zhao">JINGXIAN ZHAO</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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