Autor(es): Ekchariyawat Peeraya, Hamel Rodolphe, Bernard Eric, Wichit Sineewanlaya, Surasombatpattana Pornapat, Talignani Loïc, Thomas Frédéric, Choumet Valérie, Yssel Hans, Desprès Philippe, Briant Laurence, Missé Dorothée

Resumo: Arboviruses represent an emerging threat to human. They are transmitted to vertebrates by the bite of infected arthropods. Early transmission to vertebrates is initiated by skin puncture - deposition of virus in this organ. However, events at the bite site remain largely unknown. Here, we report that Chikungunya virus (CHIKV) - West Nile virus (WNV), despite belonging to distinct viral families, elicit a common antiviral signature in primary human dermal fibroblasts, attesting for the up regulation of interferon signaling pathways - leading to an increased expression of IFN-?, interleukins - chemokines. Remarkably, CHIKV - WNV enhance IL-1? expression - induce maturation of caspase-1, indicating the capacity of these pathogens to elicit activation of the inflammasome program in resident skin cells. CHIKV - WNV also induce the expression of the inflammasome sensor AIM2 in dermal fibroblasts, whereas inhibition of caspase-1 - AIM2 with siRNA interferes with both CHIKV- - WNV-induced IL-1? production by these cells. Finally, inhibition of the inflammasome via caspase-1 silencing was found to enhance CHIKV replication in dermal fibroblasts. Together, these results indicate that the skin contributes to the pro-inflammatory - anti-viral microenvironment via the activation of the inflammasome in the early stages following infection with arboviruses.

Palavras-Chave: AIM2; Arbovirus; Caspase 1; Chikungunya virus; Inflammasome; West Nile virus

Imprenta: Infection, Genetics and Evolution, v. 32, p. 401-408, 2015

Identificador do objeto digital: 10.1016/j.meegid.2015.03.025

Descritores: Chikungunya virus - Arbovirus ; Chikungunya virus - Biosynthesis ; Chikungunya virus - Cell ; Chikungunya virus - Cytopathology ; Chikungunya virus - DNA ; Chikungunya virus - Flaviviridae ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Cytokines ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Transmission ; Chikungunya virus - Immunology

Data de publicação: 2015