title: 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 (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.
authors: INSERM, U758, Ecole Normale Supérieure de Lyon, Lyon, France.
authors: Cyrille
authors: C
authors: Mathieu
authors: Vanessa
authors: V
authors: Guillaume
authors: Valentina A
authors: VA
authors: Volchkova
authors: Christine
authors: C
authors: Pohl
authors: Frederique
authors: F
authors: Jacquot
authors: Ren Yih
authors: RY
authors: Looi
authors: Kum Thong
authors: KT
authors: Wong
authors: Catherine
authors: C
authors: Legras-Lachuer
authors: Viktor E
authors: VE
authors: Volchkov
authors: Joel
authors: J
authors: Lachuer
authors: Branka
authors: B
authors: Horvat
mesh_terms: D000818:Animals; D006224:Cricetinae; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000821:virology; D015967:Gene Expression Regulation, Viral; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation; D008647:Mesocricetus; D008833:Microcirculation; D045405:Nipah Virus / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics* / Q000502:physiology*; D011994:Recombinant Proteins / Q000737:chemistry; D013997:Time Factors; D014471:Umbilical Veins / Q000166:cytology; D014764:Viral Proteins / Q000235:genetics* / Q000502:physiology*; D014774:Virulence
chemical_list: C543302:C protein, Nipah virus; D016207:Cytokines; D010750:Phosphoproteins; D011994:Recombinant Proteins; D014764:Viral Proteins