Autor(es)Teng Terk-Shin, Foo Suan-Sin, Simamarta Diane, Lum Fok-Moon, Teo Teck-Hui, Lulla Aleksei, Yeo Nicholas K W, Koh Esther G L, Chow Angela, Leo Yee-Sin, Merits Andres, Chin Keh-Chuang, Ng Lisa F P

ResumoChikungunya virus (CHIKV) is a mosquito-borne arthralgia arbovirus that is reemergent in sub-Saharan Africa - Southeast Asia. CHIKV infection has been shown to be self-limiting, but the molecular mechanisms of the innate immune response that control CHIKV replication remain undefined. Here, longitudinal transcriptional analyses of PBMCs from a cohort of CHIKV-infected patients revealed that type I IFNs controlled CHIKV infection via RSAD2 (which encodes viperin), an enigmatic multifunctional IFN-stimulated gene (ISG). Viperin was highly induced in monocytes, the major target cell of CHIKV in blood. Anti-CHIKV functions of viperin were dependent on its localization in the ER, - the N-terminal amphipathic ?-helical domain was crucial for its antiviral activity in controlling CHIKV replication. Furthermore, mice lacking Rsad2 had higher viremia - severe joint inflammation compared with wild-type mice. Our data demonstrate that viperin is a critical antiviral host protein that controls CHIKV infection - provide a preclinical basis for the design of effective control strategies against CHIKV - other reemerging arthrogenic alphaviruses.

ImprentaThe Journal of Clinical Investigation, v. 122, n. 12, p. 4447-4460, 2012

DescritoresChikungunya virus - Arbovirus ; Chikungunya virus - Biosynthesis ; Chikungunya virus - Cell ; Chikungunya virus - Cytopathology ; Chikungunya virus - Immune response ; Chikungunya virus - Molecular structure ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Immune response ; Chikungunya virus - Inflammation ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Molecular screening ; Chikungunya virus - Immunology ; Chikungunya virus - Public health

Data de Publicação:2012