Nonstructural Nipah virus C protein regulates both the early host proinflammatory response and viral virulence.
Identifieur interne : 000255 ( Main/Exploration ); précédent : 000254; suivant : 000256Nonstructural Nipah virus C protein regulates both the early host proinflammatory response and viral virulence.
Auteurs : Cyrille Mathieu [France] ; Vanessa Guillaume ; Valentina A. Volchkova ; Christine Pohl ; Frederique Jacquot ; Ren Yih Looi ; Kum Thong Wong ; Catherine Legras-Lachuer ; Viktor E. Volchkov ; Joel Lachuer ; Branka HorvatSource :
- Journal of virology [ 1098-5514 ] ; 2012.
English descriptors
- KwdEn :
- Animals, Cricetinae, Cytokines (metabolism), Endothelial Cells (cytology), Endothelial Cells (virology), Gene Expression Regulation, Viral, HEK293 Cells, Humans, Inflammation, Mesocricetus, Microcirculation, Nipah Virus (metabolism), Phosphoproteins (genetics), Phosphoproteins (physiology), Recombinant Proteins (chemistry), Time Factors, Umbilical Veins (cytology), Viral Proteins (genetics), Viral Proteins (physiology), Virulence.
- MESH :
- chemical , chemistry : Recombinant Proteins.
- chemical , genetics : Phosphoproteins, Viral Proteins.
- chemical , metabolism : Cytokines.
- cytology : Endothelial Cells, Umbilical Veins.
- metabolism : Nipah Virus.
- chemical , physiology : Phosphoproteins, Viral Proteins.
- virology : Endothelial Cells.
- Animals, Cricetinae, Gene Expression Regulation, Viral, HEK293 Cells, Humans, Inflammation, Mesocricetus, Microcirculation, Time Factors, Virulence.
Abstract
Nipah virus (NiV) is a highly pathogenic, negative-strand RNA paramyxovirus that has recently emerged from flying foxes to cause serious human disease. We have analyzed the role of the nonstructural NiV C protein in viral immunopathogenesis using recombinant virus lacking the expression of NiV C (NiVΔC). While wild-type NiV was highly pathogenic in the hamster animal model, NiVΔC was strongly attenuated. Replication of NiVΔC was followed by the production of NiV-specific antibodies and associated with higher recruitment of inflammatory cells and less intensive histopathological lesions in different organs than in wild-type-NiV-infected animals. To analyze the molecular basis of NiVΔC attenuation, we studied early changes in gene expression in infected primary human endothelial cells, a major cellular target of NiV infection. The transcriptomic approach revealed the striking difference between wild-type and mutant NiV in the expression of genes involved in immunity, with the particularly interesting differential patterns of proinflammatory cytokines. Compared to wild-type virus, NiVΔC induced increased expression of interleukin 1 beta (IL-1β), IL-8, CXCL2, CXCL3, CXCL6, CCL20, and beta interferon. Furthermore, the expression of NiV C in stably transfected cells decreased the production of the same panel of cytokines, revealing a role of the C protein in the regulation of cytokine balance. Together, these results suggest that NiV C regulates expression of proinflammatory cytokines, therefore providing a signal responsible for the coordination of leukocyte recruitment and the chemokine-induced immune response and controlling the lethal outcome of the infection.
DOI: 10.1128/JVI.01203-12
PubMed: 22837207
Affiliations:
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Le document en format XML
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Volchkova</name></author><author><name sortKey="Pohl, Christine" sort="Pohl, Christine" uniqKey="Pohl C" first="Christine" last="Pohl">Christine Pohl</name></author><author><name sortKey="Jacquot, Frederique" sort="Jacquot, Frederique" uniqKey="Jacquot F" first="Frederique" last="Jacquot">Frederique Jacquot</name></author><author><name sortKey="Looi, Ren Yih" sort="Looi, Ren Yih" uniqKey="Looi R" first="Ren Yih" last="Looi">Ren Yih Looi</name></author><author><name sortKey="Wong, Kum Thong" sort="Wong, Kum Thong" uniqKey="Wong K" first="Kum Thong" last="Wong">Kum Thong Wong</name></author><author><name sortKey="Legras Lachuer, Catherine" sort="Legras Lachuer, Catherine" uniqKey="Legras Lachuer C" first="Catherine" last="Legras-Lachuer">Catherine Legras-Lachuer</name></author><author><name sortKey="Volchkov, Viktor E" sort="Volchkov, Viktor E" uniqKey="Volchkov V" first="Viktor E" last="Volchkov">Viktor E. Volchkov</name></author><author><name sortKey="Lachuer, Joel" sort="Lachuer, Joel" uniqKey="Lachuer J" first="Joel" last="Lachuer">Joel Lachuer</name></author><author><name sortKey="Horvat, Branka" sort="Horvat, Branka" uniqKey="Horvat B" first="Branka" last="Horvat">Branka Horvat</name></author></analytic><series><title level="j">Journal of virology</title><idno type="eISSN">1098-5514</idno><imprint><date when="2012" type="published">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Cricetinae</term><term>Cytokines (metabolism)</term><term>Endothelial Cells (cytology)</term><term>Endothelial Cells (virology)</term><term>Gene Expression Regulation, Viral</term><term>HEK293 Cells</term><term>Humans</term><term>Inflammation</term><term>Mesocricetus</term><term>Microcirculation</term><term>Nipah Virus (metabolism)</term><term>Phosphoproteins (genetics)</term><term>Phosphoproteins (physiology)</term><term>Recombinant Proteins (chemistry)</term><term>Time Factors</term><term>Umbilical Veins (cytology)</term><term>Viral Proteins (genetics)</term><term>Viral Proteins (physiology)</term><term>Virulence</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Recombinant Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Phosphoproteins</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Cytokines</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Endothelial Cells</term><term>Umbilical Veins</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Nipah Virus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Phosphoproteins</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Endothelial Cells</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cricetinae</term><term>Gene Expression Regulation, Viral</term><term>HEK293 Cells</term><term>Humans</term><term>Inflammation</term><term>Mesocricetus</term><term>Microcirculation</term><term>Time Factors</term><term>Virulence</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Nipah virus (NiV) is a highly pathogenic, negative-strand RNA paramyxovirus that has recently emerged from flying foxes to cause serious human disease. We have analyzed the role of the nonstructural NiV C protein in viral immunopathogenesis using recombinant virus lacking the expression of NiV C (NiVΔC). While wild-type NiV was highly pathogenic in the hamster animal model, NiVΔC was strongly attenuated. Replication of NiVΔC was followed by the production of NiV-specific antibodies and associated with higher recruitment of inflammatory cells and less intensive histopathological lesions in different organs than in wild-type-NiV-infected animals. To analyze the molecular basis of NiVΔC attenuation, we studied early changes in gene expression in infected primary human endothelial cells, a major cellular target of NiV infection. The transcriptomic approach revealed the striking difference between wild-type and mutant NiV in the expression of genes involved in immunity, with the particularly interesting differential patterns of proinflammatory cytokines. Compared to wild-type virus, NiVΔC induced increased expression of interleukin 1 beta (IL-1β), IL-8, CXCL2, CXCL3, CXCL6, CCL20, and beta interferon. Furthermore, the expression of NiV C in stably transfected cells decreased the production of the same panel of cytokines, revealing a role of the C protein in the regulation of cytokine balance. Together, these results suggest that NiV C regulates expression of proinflammatory cytokines, therefore providing a signal responsible for the coordination of leukocyte recruitment and the chemokine-induced immune response and controlling the lethal outcome of the infection.</div></front></TEI><affiliations><list><country><li>France</li></country><region><li>Auvergne-Rhône-Alpes</li><li>Rhône-Alpes</li></region><settlement><li>Lyon</li></settlement></list><tree><noCountry><name sortKey="Guillaume, Vanessa" sort="Guillaume, Vanessa" uniqKey="Guillaume V" first="Vanessa" last="Guillaume">Vanessa Guillaume</name><name sortKey="Horvat, Branka" sort="Horvat, Branka" uniqKey="Horvat B" first="Branka" last="Horvat">Branka Horvat</name><name sortKey="Jacquot, Frederique" sort="Jacquot, Frederique" uniqKey="Jacquot F" first="Frederique" last="Jacquot">Frederique Jacquot</name><name sortKey="Lachuer, Joel" sort="Lachuer, Joel" uniqKey="Lachuer J" first="Joel" last="Lachuer">Joel Lachuer</name><name sortKey="Legras Lachuer, Catherine" sort="Legras Lachuer, Catherine" uniqKey="Legras Lachuer C" first="Catherine" last="Legras-Lachuer">Catherine Legras-Lachuer</name><name sortKey="Looi, Ren Yih" sort="Looi, Ren Yih" uniqKey="Looi R" first="Ren Yih" last="Looi">Ren Yih Looi</name><name sortKey="Pohl, Christine" sort="Pohl, Christine" uniqKey="Pohl C" first="Christine" last="Pohl">Christine Pohl</name><name sortKey="Volchkov, Viktor E" sort="Volchkov, Viktor E" uniqKey="Volchkov V" first="Viktor E" last="Volchkov">Viktor E. Volchkov</name><name sortKey="Volchkova, Valentina A" sort="Volchkova, Valentina A" uniqKey="Volchkova V" first="Valentina A" last="Volchkova">Valentina A. Volchkova</name><name sortKey="Wong, Kum Thong" sort="Wong, Kum Thong" uniqKey="Wong K" first="Kum Thong" last="Wong">Kum Thong Wong</name></noCountry><country name="France"><region name="Auvergne-Rhône-Alpes"><name sortKey="Mathieu, Cyrille" sort="Mathieu, Cyrille" uniqKey="Mathieu C" first="Cyrille" last="Mathieu">Cyrille Mathieu</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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