Autor(es): Fros Jelke J, Liu Wen Jun, Prow Natalie A, Geertsema Corinne, Ligtenberg Maarten, Vanlandingham Dana L, Schnettler Esther, Vlak Just M, Suhrbier Andreas, Khromykh Alexander A, Pijlman Gorben P

Resumo: Chikungunya virus (CHIKV) is an emerging human pathogen transmitted by mosquitoes. Like that of other alphaviruses, CHIKV replication causes general host shutoff, leading to severe cytopathicity in mammalian cells, - inhibits the ability of infected cells to respond to interferon (IFN). Recent research, however, suggests that alphaviruses may have additional mechanisms to circumvent the host's antiviral IFN response. Here we show that CHIKV replication is resistant to inhibition by interferon once RNA replication has been established - that CHIKV actively suppresses the antiviral IFN response by preventing IFN-induced gene expression. Both CHIKV infection - CHIKV replicon RNA replication efficiently blocked STAT1 phosphorylation -/or nuclear translocation in mammalian cells induced by either type I or type II IFN. Expression of individual CHIKV nonstructural proteins (nsPs) showed that nsP2 was a potent inhibitor of IFN-induced JAK-STAT signaling. In addition, mutations in CHIKV-nsP2 (P718S) - Sindbis virus (SINV)-nsP2 (P726S) that render alphavirus replicons noncytopathic significantly reduced JAK-STAT inhibition. This host shutoff-independent inhibition of IFN signaling by CHIKV is likely to have an important role in viral pathogenesis.

Imprenta: Journal of Virology, v. 84, n. 20, 10877-10887, 2010

Identificador do objeto digital: 10.1128/JVI.00949-10

Descritores: Chikungunya virus - Cell ; Chikungunya virus - DNA ; Chikungunya virus - Genome ; Chikungunya virus - Molecular structure ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - RNA ; Chikungunya virus - Cytokines ; Chikungunya Virus - Virus

Data de publicação: 2010

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