Nonstructural Nipah virus C protein regulates both the early host proinflammatory response and viral virulence. - Université Claude Bernard Lyon 1 Accéder directement au contenu
Article Dans Une Revue Journal of Virology Année : 2012

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

Résumé

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.

Dates et versions

hal-00965888 , version 1 (25-03-2014)

Identifiants

Citer

Cyrille Mathieu, Vanessa Guillaume, Valentina A Volchkova, Christine Pohl, Frederique Jacquot, et al.. Nonstructural Nipah virus C protein regulates both the early host proinflammatory response and viral virulence.. Journal of Virology, 2012, 86 (19), pp.10766-75. ⟨10.1128/JVI.01203-12⟩. ⟨hal-00965888⟩
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