Autor(es): Krejbich-Trotot Pascale, Denizot Melanie, Hoarau Jean-Jacques, Jaffar-B-jee Marie-Christine, Das Trina, Gasque Philippe

Resumo: Chikungunya virus (CHIKV) surprised medical workers by a massive outbreak in the Indian Ocean region, reaching Europe in 2007, with exceptional pathologies in infants - elderly patients. Although CHIKV was recently shown to persist in myoblasts, monocytes, - macrophages, we argued that robust antiviral mechanisms, including apoptosis, are essential to ward off the virus. Herein, we tested the capacity of CHIKV to mobilize the apoptotic machinery in HeLa cells as well as primary fibroblasts, making use of several inhibitors of caspases, cell blebbing, - engulfment of the apoptotic blebs by neighboring cells. CHIKV triggered apoptosis through intrinsic - extrinsic pathways. Byst-er apoptosis was also evidenced in neighboring cells in a caspase-8-dependent manner. Remarkably, by hiding in apoptotic blebs, CHIKV was able to infect neighboring cells. In HeLa cells, these events were inhibited specifically by zVAD-fmk - DEVD-cho (caspase inhibitors), blebbistatin, Y-27632 (ROCK inhibitor), - genistein, annexin V, - cytochalasin B (inhibitors of blebbing - engulfment). These CHIKV-apoptotic blebs were also capable of infecting macrophages (primary cultures, MM6- - THP1-PMA differentiated cells) otherwise refractory to infection by CHIKV alone. Remarkably, viral replication in macrophages did not yield a proinflammatory response. We describe a novel infectious mechanism by which CHIKV invades host cells - escapes the host response.

Imprenta: FASEB Journal, v. 25, n. 1, p. 314-325, 2011

Identificador do objeto digital: 10.1096/fj.10-164178

Descritores: Chikungunya virus - Biosynthesis ; Chikungunya virus - Cell ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Immunopathology ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus

Data de publicação: 2011

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