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J Clin Invest. 2012 Dec;122(12):4447-60. doi: 10.1172/JCI63120. Epub 2012 Nov 19.

Viperin restricts chikungunya virus replication and pathology.

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1
Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore.

Abstract

Chikungunya virus (CHIKV) is a mosquito-borne arthralgia arbovirus that is reemergent in sub-Saharan Africa and 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, and the N-terminal amphipathic α-helical domain was crucial for its antiviral activity in controlling CHIKV replication. Furthermore, mice lacking Rsad2 had higher viremia and severe joint inflammation compared with wild-type mice. Our data demonstrate that viperin is a critical antiviral host protein that controls CHIKV infection and provide a preclinical basis for the design of effective control strategies against CHIKV and other reemerging arthrogenic alphaviruses.

PMID:
23160199
PMCID:
PMC3533538
DOI:
10.1172/JCI63120
[Indexed for MEDLINE]
Free PMC Article
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