Viperin restricts chikungunya virus replication and pathology.
J Clin Invest
; 122(12): 4447-60, 2012 Dec.
Article
em En
| MEDLINE
| ID: mdl-23160199
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Replicação Viral
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Proteínas
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Vírus Chikungunya
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Infecções por Alphavirus
Tipo de estudo:
Observational_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article