Dengue virus-specific CD4+ and CD8+ T lymphocytes target NS1, NS3 and NS5 in infected Indian rhesus macaques
Identifieur interne : 000496 ( Istex/Checkpoint ); précédent : 000495; suivant : 000497Dengue virus-specific CD4+ and CD8+ T lymphocytes target NS1, NS3 and NS5 in infected Indian rhesus macaques
Auteurs : Katherine M. Mladinich [États-Unis] ; Shari M. Piaskowski [États-Unis] ; Richard Rudersdorf [États-Unis] ; Christopher M. Eernisse [États-Unis] ; Kim L. Weisgrau [États-Unis] ; Mauricio A. Martins [États-Unis] ; Jessica R. Furlott [États-Unis] ; Charalambos D. Partidos [États-Unis] ; Joseph N. Brewoo [États-Unis] ; Jorge E. Osorio [États-Unis] ; Nancy A. Wilson [États-Unis] ; Eva G. Rakasz [États-Unis] ; David I. Watkins [États-Unis]Source :
- Immunogenetics [ 0093-7711 ] ; 2012-02-01.
English descriptors
Abstract
Abstract: Every year, Dengue virus (DENV) infects approximately 100 million people. There are currently several vaccines undergoing clinical studies, but most target the induction of neutralizing antibodies. Unfortunately, DENV infection can be enhanced by subneutralizing levels of antibodies that bind virions and deliver them to cells of the myeloid lineage, thereby increasing viral replication (termed antibody-dependent enhancement [ADE]). T lymphocyte-based vaccines may offer an alternative that avoids ADE. The goal of our study was to describe the cellular immune response generated after primary DENV infection in Indian rhesus macaques. We infected eight rhesus macaques with 105 plaque-forming units (PFU) of DENV serotype 2 (DENV2) New Guinea C (NGC) strain, and monitored viral load and the cellular immune response to the virus. Viral replication peaked at day 4 post-infection and was resolved by day 10. DENV-specific CD4+ and CD8+ T lymphocytes targeted nonstructural (NS) 1, NS3 and NS5 proteins after resolution of peak viremia. DENV-specific CD4+ cells expressed interferon-gamma (IFN-γ) along with tumor necrosis factor-alpha (TNF-α), interleukin-2 (IL-2), and macrophage inflammatory protein-1 beta (MIP-1β). In comparison, DENV-specific CD8+ cells expressed IFN-γ in addition to MIP-1β and TNF-α and were positive for the degranulation marker CD107a. Interestingly, a fraction of the DENV-specific CD4+ cells also stained for CD107a, suggesting that they might be cytotoxic. Our results provide a more complete understanding of the cellular immune response during DENV infection in rhesus macaques and contribute to the development of rhesus macaques as an animal model for DENV vaccine and pathogenicity studies.
Url:
DOI: 10.1007/s00251-011-0566-0
Affiliations:
Links toward previous steps (curation, corpus...)
Links to Exploration step
ISTEX:7F606692732506B8032C69042A0A4704A90A9656Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Dengue virus-specific CD4+ and CD8+ T lymphocytes target NS1, NS3 and NS5 in infected Indian rhesus macaques</title><author><name sortKey="Mladinich, Katherine M" sort="Mladinich, Katherine M" uniqKey="Mladinich K" first="Katherine M." last="Mladinich">Katherine M. Mladinich</name></author><author><name sortKey="Piaskowski, Shari M" sort="Piaskowski, Shari M" uniqKey="Piaskowski S" first="Shari M." last="Piaskowski">Shari M. Piaskowski</name></author><author><name sortKey="Rudersdorf, Richard" sort="Rudersdorf, Richard" uniqKey="Rudersdorf R" first="Richard" last="Rudersdorf">Richard Rudersdorf</name></author><author><name sortKey="Eernisse, Christopher M" sort="Eernisse, Christopher M" uniqKey="Eernisse C" first="Christopher M." last="Eernisse">Christopher M. Eernisse</name></author><author><name sortKey="Weisgrau, Kim L" sort="Weisgrau, Kim L" uniqKey="Weisgrau K" first="Kim L." last="Weisgrau">Kim L. Weisgrau</name></author><author><name sortKey="Martins, Mauricio A" sort="Martins, Mauricio A" uniqKey="Martins M" first="Mauricio A." last="Martins">Mauricio A. Martins</name></author><author><name sortKey="Furlott, Jessica R" sort="Furlott, Jessica R" uniqKey="Furlott J" first="Jessica R." last="Furlott">Jessica R. Furlott</name></author><author><name sortKey="Partidos, Charalambos D" sort="Partidos, Charalambos D" uniqKey="Partidos C" first="Charalambos D." last="Partidos">Charalambos D. Partidos</name></author><author><name sortKey="Brewoo, Joseph N" sort="Brewoo, Joseph N" uniqKey="Brewoo J" first="Joseph N." last="Brewoo">Joseph N. Brewoo</name></author><author><name sortKey="Osorio, Jorge E" sort="Osorio, Jorge E" uniqKey="Osorio J" first="Jorge E." last="Osorio">Jorge E. Osorio</name></author><author><name sortKey="Wilson, Nancy A" sort="Wilson, Nancy A" uniqKey="Wilson N" first="Nancy A." last="Wilson">Nancy A. Wilson</name></author><author><name sortKey="Rakasz, Eva G" sort="Rakasz, Eva G" uniqKey="Rakasz E" first="Eva G." last="Rakasz">Eva G. Rakasz</name></author><author><name sortKey="Watkins, David I" sort="Watkins, David I" uniqKey="Watkins D" first="David I." last="Watkins">David I. Watkins</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:7F606692732506B8032C69042A0A4704A90A9656</idno><date when="2011" year="2011">2011</date><idno type="doi">10.1007/s00251-011-0566-0</idno><idno type="url">https://api.istex.fr/ark:/67375/VQC-MB0DJTP2-0/fulltext.pdf</idno><idno type="wicri:Area/Istex/Corpus">000A28</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">000A28</idno><idno type="wicri:Area/Istex/Curation">000A28</idno><idno type="wicri:Area/Istex/Checkpoint">000496</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Checkpoint">000496</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Dengue virus-specific CD4+ and CD8+ T lymphocytes target NS1, NS3 and NS5 in infected Indian rhesus macaques</title><author><name sortKey="Mladinich, Katherine M" sort="Mladinich, Katherine M" uniqKey="Mladinich K" first="Katherine M." last="Mladinich">Katherine M. Mladinich</name><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Microbiology Doctoral Training Program, University of Wisconsin–Madison, 1326 Microbial Sciences, 1550 Linden Drive, 53706, Madison, WI</wicri:regionArea><orgName type="university">Université du Wisconsin à Madison</orgName><placeName><settlement type="city">Madison (Wisconsin)</settlement><region type="state">Wisconsin</region></placeName></affiliation></author><author><name sortKey="Piaskowski, Shari M" sort="Piaskowski, Shari M" uniqKey="Piaskowski S" first="Shari M." last="Piaskowski">Shari M. Piaskowski</name><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Laboratory Medicine, University of Wisconsin–Madison, 555 Science Dr, 53711, Madison, WI</wicri:regionArea><orgName type="university">Université du Wisconsin à Madison</orgName><placeName><settlement type="city">Madison (Wisconsin)</settlement><region type="state">Wisconsin</region></placeName></affiliation></author><author><name sortKey="Rudersdorf, Richard" sort="Rudersdorf, Richard" uniqKey="Rudersdorf R" first="Richard" last="Rudersdorf">Richard Rudersdorf</name><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Laboratory Medicine, University of Wisconsin–Madison, 555 Science Dr, 53711, Madison, WI</wicri:regionArea><orgName type="university">Université du Wisconsin à Madison</orgName><placeName><settlement type="city">Madison (Wisconsin)</settlement><region type="state">Wisconsin</region></placeName></affiliation></author><author><name sortKey="Eernisse, Christopher M" sort="Eernisse, Christopher M" uniqKey="Eernisse C" first="Christopher M." last="Eernisse">Christopher M. Eernisse</name><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Laboratory Medicine, University of Wisconsin–Madison, 555 Science Dr, 53711, Madison, WI</wicri:regionArea><orgName type="university">Université du Wisconsin à Madison</orgName><placeName><settlement type="city">Madison (Wisconsin)</settlement><region type="state">Wisconsin</region></placeName></affiliation><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wisconsin National Primate Research Center, University of Wisconsin–Madison, Madison, WI</wicri:regionArea><orgName type="university">Université du Wisconsin à Madison</orgName><placeName><settlement type="city">Madison (Wisconsin)</settlement><region type="state">Wisconsin</region></placeName></affiliation></author><author><name sortKey="Weisgrau, Kim L" sort="Weisgrau, Kim L" uniqKey="Weisgrau K" first="Kim L." last="Weisgrau">Kim L. Weisgrau</name><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Laboratory Medicine, University of Wisconsin–Madison, 555 Science Dr, 53711, Madison, WI</wicri:regionArea><orgName type="university">Université du Wisconsin à Madison</orgName><placeName><settlement type="city">Madison (Wisconsin)</settlement><region type="state">Wisconsin</region></placeName></affiliation><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wisconsin National Primate Research Center, University of Wisconsin–Madison, Madison, WI</wicri:regionArea><orgName type="university">Université du Wisconsin à Madison</orgName><placeName><settlement type="city">Madison (Wisconsin)</settlement><region type="state">Wisconsin</region></placeName></affiliation></author><author><name sortKey="Martins, Mauricio A" sort="Martins, Mauricio A" uniqKey="Martins M" first="Mauricio A." last="Martins">Mauricio A. Martins</name><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Laboratory Medicine, University of Wisconsin–Madison, 555 Science Dr, 53711, Madison, WI</wicri:regionArea><orgName type="university">Université du Wisconsin à Madison</orgName><placeName><settlement type="city">Madison (Wisconsin)</settlement><region type="state">Wisconsin</region></placeName></affiliation></author><author><name sortKey="Furlott, Jessica R" sort="Furlott, Jessica R" uniqKey="Furlott J" first="Jessica R." last="Furlott">Jessica R. Furlott</name><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Laboratory Medicine, University of Wisconsin–Madison, 555 Science Dr, 53711, Madison, WI</wicri:regionArea><orgName type="university">Université du Wisconsin à Madison</orgName><placeName><settlement type="city">Madison (Wisconsin)</settlement><region type="state">Wisconsin</region></placeName></affiliation><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wisconsin National Primate Research Center, University of Wisconsin–Madison, Madison, WI</wicri:regionArea><orgName type="university">Université du Wisconsin à Madison</orgName><placeName><settlement type="city">Madison (Wisconsin)</settlement><region type="state">Wisconsin</region></placeName></affiliation></author><author><name sortKey="Partidos, Charalambos D" sort="Partidos, Charalambos D" uniqKey="Partidos C" first="Charalambos D." last="Partidos">Charalambos D. Partidos</name><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathobiological Sciences, University of Wisconsin–Madison, 119 AHABS, 1656 Linden Drive, 53706, Madison, WI</wicri:regionArea><orgName type="university">Université du Wisconsin à Madison</orgName><placeName><settlement type="city">Madison (Wisconsin)</settlement><region type="state">Wisconsin</region></placeName></affiliation></author><author><name sortKey="Brewoo, Joseph N" sort="Brewoo, Joseph N" uniqKey="Brewoo J" first="Joseph N." last="Brewoo">Joseph N. Brewoo</name><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathobiological Sciences, University of Wisconsin–Madison, 119 AHABS, 1656 Linden Drive, 53706, Madison, WI</wicri:regionArea><orgName type="university">Université du Wisconsin à Madison</orgName><placeName><settlement type="city">Madison (Wisconsin)</settlement><region type="state">Wisconsin</region></placeName></affiliation></author><author><name sortKey="Osorio, Jorge E" sort="Osorio, Jorge E" uniqKey="Osorio J" first="Jorge E." last="Osorio">Jorge E. Osorio</name><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathobiological Sciences, University of Wisconsin–Madison, 119 AHABS, 1656 Linden Drive, 53706, Madison, WI</wicri:regionArea><orgName type="university">Université du Wisconsin à Madison</orgName><placeName><settlement type="city">Madison (Wisconsin)</settlement><region type="state">Wisconsin</region></placeName></affiliation></author><author><name sortKey="Wilson, Nancy A" sort="Wilson, Nancy A" uniqKey="Wilson N" first="Nancy A." last="Wilson">Nancy A. Wilson</name><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Laboratory Medicine, University of Wisconsin–Madison, 555 Science Dr, 53711, Madison, WI</wicri:regionArea><orgName type="university">Université du Wisconsin à Madison</orgName><placeName><settlement type="city">Madison (Wisconsin)</settlement><region type="state">Wisconsin</region></placeName></affiliation><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wisconsin National Primate Research Center, University of Wisconsin–Madison, Madison, WI</wicri:regionArea><orgName type="university">Université du Wisconsin à Madison</orgName><placeName><settlement type="city">Madison (Wisconsin)</settlement><region type="state">Wisconsin</region></placeName></affiliation></author><author><name sortKey="Rakasz, Eva G" sort="Rakasz, Eva G" uniqKey="Rakasz E" first="Eva G." last="Rakasz">Eva G. Rakasz</name><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Laboratory Medicine, University of Wisconsin–Madison, 555 Science Dr, 53711, Madison, WI</wicri:regionArea><orgName type="university">Université du Wisconsin à Madison</orgName><placeName><settlement type="city">Madison (Wisconsin)</settlement><region type="state">Wisconsin</region></placeName></affiliation><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wisconsin National Primate Research Center, University of Wisconsin–Madison, Madison, WI</wicri:regionArea><orgName type="university">Université du Wisconsin à Madison</orgName><placeName><settlement type="city">Madison (Wisconsin)</settlement><region type="state">Wisconsin</region></placeName></affiliation></author><author><name sortKey="Watkins, David I" sort="Watkins, David I" uniqKey="Watkins D" first="David I." last="Watkins">David I. Watkins</name><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology and Laboratory Medicine, University of Wisconsin–Madison, 555 Science Dr, 53711, Madison, WI</wicri:regionArea><orgName type="university">Université du Wisconsin à Madison</orgName><placeName><settlement type="city">Madison (Wisconsin)</settlement><region type="state">Wisconsin</region></placeName></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>University of Wisconsin, 555 Science Drive, 53711, Madison, WI</wicri:regionArea><wicri:noRegion>WI</wicri:noRegion></affiliation><affiliation wicri:level="1"><country wicri:rule="url">États-Unis</country></affiliation></author></analytic><monogr></monogr><series><title level="j">Immunogenetics</title><title level="j" type="abbrev">Immunogenetics</title><idno type="ISSN">0093-7711</idno><idno type="eISSN">1432-1211</idno><imprint><publisher>Springer-Verlag</publisher><pubPlace>Berlin/Heidelberg</pubPlace><date type="published" when="2012-02-01">2012-02-01</date><biblScope unit="volume">64</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="111">111</biblScope><biblScope unit="page" to="121">121</biblScope></imprint><idno type="ISSN">0093-7711</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0093-7711</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>CD8+ and CD4+ T lymphocytes</term><term>Dengue</term><term>Indian rhesus macaque</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: Every year, Dengue virus (DENV) infects approximately 100 million people. There are currently several vaccines undergoing clinical studies, but most target the induction of neutralizing antibodies. Unfortunately, DENV infection can be enhanced by subneutralizing levels of antibodies that bind virions and deliver them to cells of the myeloid lineage, thereby increasing viral replication (termed antibody-dependent enhancement [ADE]). T lymphocyte-based vaccines may offer an alternative that avoids ADE. The goal of our study was to describe the cellular immune response generated after primary DENV infection in Indian rhesus macaques. We infected eight rhesus macaques with 105 plaque-forming units (PFU) of DENV serotype 2 (DENV2) New Guinea C (NGC) strain, and monitored viral load and the cellular immune response to the virus. Viral replication peaked at day 4 post-infection and was resolved by day 10. DENV-specific CD4+ and CD8+ T lymphocytes targeted nonstructural (NS) 1, NS3 and NS5 proteins after resolution of peak viremia. DENV-specific CD4+ cells expressed interferon-gamma (IFN-γ) along with tumor necrosis factor-alpha (TNF-α), interleukin-2 (IL-2), and macrophage inflammatory protein-1 beta (MIP-1β). In comparison, DENV-specific CD8+ cells expressed IFN-γ in addition to MIP-1β and TNF-α and were positive for the degranulation marker CD107a. Interestingly, a fraction of the DENV-specific CD4+ cells also stained for CD107a, suggesting that they might be cytotoxic. Our results provide a more complete understanding of the cellular immune response during DENV infection in rhesus macaques and contribute to the development of rhesus macaques as an animal model for DENV vaccine and pathogenicity studies.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Wisconsin</li></region><settlement><li>Madison (Wisconsin)</li></settlement><orgName><li>Université du Wisconsin à Madison</li></orgName></list><tree><country name="États-Unis"><region name="Wisconsin"><name sortKey="Mladinich, Katherine M" sort="Mladinich, Katherine M" uniqKey="Mladinich K" first="Katherine M." last="Mladinich">Katherine M. Mladinich</name></region><name sortKey="Brewoo, Joseph N" sort="Brewoo, Joseph N" uniqKey="Brewoo J" first="Joseph N." last="Brewoo">Joseph N. Brewoo</name><name sortKey="Eernisse, Christopher M" sort="Eernisse, Christopher M" uniqKey="Eernisse C" first="Christopher M." last="Eernisse">Christopher M. Eernisse</name><name sortKey="Eernisse, Christopher M" sort="Eernisse, Christopher M" uniqKey="Eernisse C" first="Christopher M." last="Eernisse">Christopher M. Eernisse</name><name sortKey="Furlott, Jessica R" sort="Furlott, Jessica R" uniqKey="Furlott J" first="Jessica R." last="Furlott">Jessica R. Furlott</name><name sortKey="Furlott, Jessica R" sort="Furlott, Jessica R" uniqKey="Furlott J" first="Jessica R." last="Furlott">Jessica R. Furlott</name><name sortKey="Martins, Mauricio A" sort="Martins, Mauricio A" uniqKey="Martins M" first="Mauricio A." last="Martins">Mauricio A. Martins</name><name sortKey="Osorio, Jorge E" sort="Osorio, Jorge E" uniqKey="Osorio J" first="Jorge E." last="Osorio">Jorge E. Osorio</name><name sortKey="Partidos, Charalambos D" sort="Partidos, Charalambos D" uniqKey="Partidos C" first="Charalambos D." last="Partidos">Charalambos D. Partidos</name><name sortKey="Piaskowski, Shari M" sort="Piaskowski, Shari M" uniqKey="Piaskowski S" first="Shari M." last="Piaskowski">Shari M. Piaskowski</name><name sortKey="Rakasz, Eva G" sort="Rakasz, Eva G" uniqKey="Rakasz E" first="Eva G." last="Rakasz">Eva G. Rakasz</name><name sortKey="Rakasz, Eva G" sort="Rakasz, Eva G" uniqKey="Rakasz E" first="Eva G." last="Rakasz">Eva G. Rakasz</name><name sortKey="Rudersdorf, Richard" sort="Rudersdorf, Richard" uniqKey="Rudersdorf R" first="Richard" last="Rudersdorf">Richard Rudersdorf</name><name sortKey="Watkins, David I" sort="Watkins, David I" uniqKey="Watkins D" first="David I." last="Watkins">David I. Watkins</name><name sortKey="Watkins, David I" sort="Watkins, David I" uniqKey="Watkins D" first="David I." last="Watkins">David I. Watkins</name><name sortKey="Watkins, David I" sort="Watkins, David I" uniqKey="Watkins D" first="David I." last="Watkins">David I. Watkins</name><name sortKey="Weisgrau, Kim L" sort="Weisgrau, Kim L" uniqKey="Weisgrau K" first="Kim L." last="Weisgrau">Kim L. Weisgrau</name><name sortKey="Weisgrau, Kim L" sort="Weisgrau, Kim L" uniqKey="Weisgrau K" first="Kim L." last="Weisgrau">Kim L. Weisgrau</name><name sortKey="Wilson, Nancy A" sort="Wilson, Nancy A" uniqKey="Wilson N" first="Nancy A." last="Wilson">Nancy A. Wilson</name><name sortKey="Wilson, Nancy A" sort="Wilson, Nancy A" uniqKey="Wilson N" first="Nancy A." last="Wilson">Nancy A. Wilson</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/MersV1/Data/Istex/Checkpoint
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000496 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Istex/Checkpoint/biblio.hfd -nk 000496 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= MersV1
|flux= Istex
|étape= Checkpoint
|type= RBID
|clé= ISTEX:7F606692732506B8032C69042A0A4704A90A9656
|texte= Dengue virus-specific CD4+ and CD8+ T lymphocytes target NS1, NS3 and NS5 in infected Indian rhesus macaques
}}
| This area was generated with Dilib version V0.6.33. |  |