AustralieFrV1, Main, Exploration, bibRecord, 005B30

Interferon Response Factors 3 and 7 Protect against Chikungunya Virus Hemorrhagic Fever and Shock

Identifieur interne : 005B30 ( Main/Exploration ); précédent : 005B29; suivant : 005B31

Interferon Response Factors 3 and 7 Protect against Chikungunya Virus Hemorrhagic Fever and Shock

Auteurs : Penny A. Rudd [Australie] ; Jane Wilson [Australie] ; Joy Gardner [Australie] ; Thibaut Larcher [France] ; Candice Babarit [France] ; Thuy T. Le [Australie] ; Itaru Anraku [Australie] ; Yutaro Kumagai [Japon] ; Yueh-Ming Loo [États-Unis] ; Michael Jr Gale [États-Unis] ; Shizuo Akira [Japon] ; Alexander A. Khromykh [Australie] ; Andreas Suhrbier [Australie]

Source :

Journal of virology [ 0022-538X ] ; 2012.

RBID : Pascal:12-0360858

Descripteurs français

Pascal (Inist)
- Virus Chikungunya, Interféron, Fièvre hémorragique.

English descriptors

KwdEn :
- Chikungunya virus, Hemorrhagic fever, Interferon.

Abstract

Chikungunya virus (CHIKV) infections can produce severe disease and mortality. Here we show that CHIKV infection of adult mice deficient in interferon response factors 3 and 7 (IRF3/7^-/-) is lethal. Mortality was associated with undetectable levels of alpha/beta interferon (IFN-α/β) in serum, ∼50- and ∼ 10-fold increases in levels of IFN-γ and tumor necrosis factor (TNF), respectively, increased virus replication, edema, vasculitis, hemorrhage, fever followed by hypothermia, oliguria, thrombocytopenia, and raised hematocrits. These features are consistent with hemorrhagic shock and were also evident in infected IFN-α/β receptor-deficient mice. In situ hybridization suggested CHIKV infection of endothelium, fibroblasts, skeletal muscle, mononuclear cells, chondrocytes, and keratinocytes in IRF3/7^-/- mice; all but the latter two stained positive in wild-type mice. Vaccination protected IRF3/7^-/- mice, suggesting that defective antibody responses were not responsible for mortality. IPS-1- and TRIF-dependent pathways were primarily responsible for IFN-α/β induction, with IRF7 being upregulated > 100-fold in infected wild-type mice. These studies suggest that inadequate IFN-a/β responses following virus infection can be sufficient to induce hemorrhagic fever and shock, a finding with implications for understanding severe CHIKV disease and dengue hemorrhagic fever/dengue shock syndrome.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3446587

Affiliations:

Le document en format XML

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<sZ>7 aut.</sZ>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>Australie</country>
<wicri:noRegion>Queensland Institute of Medical Research</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Australian Infectious Diseases Research Centre, School of Chemistry & Molecular Biosciences, University of Queensland</s1>
<s2>Brisbane, Queensland</s2>
<s3>AUS</s3>
<sZ>1 aut.</sZ>
<sZ>12 aut.</sZ>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>Australie</country>
<wicri:noRegion>Brisbane, Queensland</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="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>Chikungunya virus</term>
<term>Hemorrhagic fever</term>
<term>Interferon</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Virus Chikungunya</term>
<term>Interféron</term>
<term>Fièvre hémorragique</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Chikungunya virus (CHIKV) infections can produce severe disease and mortality. Here we show that CHIKV infection of adult mice deficient in interferon response factors 3 and 7 (IRF3/7<sup>-/-</sup>
) is lethal. Mortality was associated with undetectable levels of alpha/beta interferon (IFN-α/β) in serum, ∼50- and ∼ 10-fold increases in levels of IFN-γ and tumor necrosis factor (TNF), respectively, increased virus replication, edema, vasculitis, hemorrhage, fever followed by hypothermia, oliguria, thrombocytopenia, and raised hematocrits. These features are consistent with hemorrhagic shock and were also evident in infected IFN-α/β receptor-deficient mice. In situ hybridization suggested CHIKV infection of endothelium, fibroblasts, skeletal muscle, mononuclear cells, chondrocytes, and keratinocytes in IRF3/7<sup>-/-</sup>
 mice; all but the latter two stained positive in wild-type mice. Vaccination protected IRF3/7<sup>-/-</sup>
 mice, suggesting that defective antibody responses were not responsible for mortality. IPS-1- and TRIF-dependent pathways were primarily responsible for IFN-α/β induction, with IRF7 being upregulated > 100-fold in infected wild-type mice. These studies suggest that inadequate IFN-a/β responses following virus infection can be sufficient to induce hemorrhagic fever and shock, a finding with implications for understanding severe CHIKV disease and dengue hemorrhagic fever/dengue shock syndrome.</div>
</front>
</TEI>
<affiliations><list><country><li>Australie</li>
<li>France</li>
<li>Japon</li>
<li>États-Unis</li>
</country>
<region><li>Pays de la Loire</li>
<li>Washington (État)</li>
</region>
<settlement><li>Nantes</li>
</settlement>
</list>
<tree><country name="Australie"><noRegion><name sortKey="Rudd, Penny A" sort="Rudd, Penny A" uniqKey="Rudd P" first="Penny A." last="Rudd">Penny A. Rudd</name>
</noRegion>
<name sortKey="Anraku, Itaru" sort="Anraku, Itaru" uniqKey="Anraku I" first="Itaru" last="Anraku">Itaru Anraku</name>
<name sortKey="Gardner, Joy" sort="Gardner, Joy" uniqKey="Gardner J" first="Joy" last="Gardner">Joy Gardner</name>
<name sortKey="Khromykh, Alexander A" sort="Khromykh, Alexander A" uniqKey="Khromykh A" first="Alexander A." last="Khromykh">Alexander A. Khromykh</name>
<name sortKey="Le, Thuy T" sort="Le, Thuy T" uniqKey="Le T" first="Thuy T." last="Le">Thuy T. Le</name>
<name sortKey="Rudd, Penny A" sort="Rudd, Penny A" uniqKey="Rudd P" first="Penny A." last="Rudd">Penny A. Rudd</name>
<name sortKey="Suhrbier, Andreas" sort="Suhrbier, Andreas" uniqKey="Suhrbier A" first="Andreas" last="Suhrbier">Andreas Suhrbier</name>
<name sortKey="Suhrbier, Andreas" sort="Suhrbier, Andreas" uniqKey="Suhrbier A" first="Andreas" last="Suhrbier">Andreas Suhrbier</name>
<name sortKey="Wilson, Jane" sort="Wilson, Jane" uniqKey="Wilson J" first="Jane" last="Wilson">Jane Wilson</name>
<name sortKey="Wilson, Jane" sort="Wilson, Jane" uniqKey="Wilson J" first="Jane" last="Wilson">Jane Wilson</name>
</country>
<country name="France"><region name="Pays de la Loire"><name sortKey="Larcher, Thibaut" sort="Larcher, Thibaut" uniqKey="Larcher T" first="Thibaut" last="Larcher">Thibaut Larcher</name>
</region>
<name sortKey="Babarit, Candice" sort="Babarit, Candice" uniqKey="Babarit C" first="Candice" last="Babarit">Candice Babarit</name>
</country>
<country name="Japon"><noRegion><name sortKey="Kumagai, Yutaro" sort="Kumagai, Yutaro" uniqKey="Kumagai Y" first="Yutaro" last="Kumagai">Yutaro Kumagai</name>
</noRegion>
<name sortKey="Akira, Shizuo" sort="Akira, Shizuo" uniqKey="Akira S" first="Shizuo" last="Akira">Shizuo Akira</name>
</country>
<country name="États-Unis"><region name="Washington (État)"><name sortKey="Loo, Yueh Ming" sort="Loo, Yueh Ming" uniqKey="Loo Y" first="Yueh-Ming" last="Loo">Yueh-Ming Loo</name>
</region>
<name sortKey="Gale, Michael Jr" sort="Gale, Michael Jr" uniqKey="Gale M" first="Michael Jr" last="Gale">Michael Jr Gale</name>
</country>
</tree>
</affiliations>
</record>

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Interferon Response Factors 3 and 7 Protect against Chikungunya Virus Hemorrhagic Fever and Shock

Interferon Response Factors 3 and 7 Protect against Chikungunya Virus Hemorrhagic Fever and Shock

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