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Nonstructural Nipah virus C protein regulates both the early host proinflammatory response and viral 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 (NiV?C). While wild-type NiV was highly pathogenic in the hamster animal model, NiV?C was strongly attenuated. Replication of NiV?C 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 NiV?C 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, NiV?C induced increased expression of interleukin 1 beta (IL-1?), 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.

SUBMITTER: Mathieu C

PROVIDER: S-EPMC3457280 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Nonstructural Nipah virus C protein regulates both the early host proinflammatory response and viral virulence.

Mathieu Cyrille C Guillaume Vanessa V Volchkova Valentina A VA Pohl Christine C Jacquot Frederique F Looi Ren Yih RY Wong Kum Thong KT Legras-Lachuer Catherine C Volchkov Viktor E VE Lachuer Joel J Horvat Branka B

Journal of virology 20120725 19

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 associate ...[more]

PMID: 22837207

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Nonstructural Nipah virus C protein regulates both the early host proinflammatory response and viral virulence.

Publications

Nonstructural Nipah virus C protein regulates both the early host proinflammatory response and viral virulence.

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