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PMID:23160199
| Citation |
Teng, TS, Foo, SS, Simamarta, D, Lum, FM, Teo, TH, Lulla, A, Yeo, NK, Koh, EG, Chow, A, Leo, YS, Merits, A, Chin, KC and Ng, LF (2012) Viperin restricts chikungunya virus replication and pathology. J. Clin. Invest. 122:4447-60 |
|---|---|
| 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. |
| Links |
PubMed PMC3533538 Online version:10.1172/JCI63120 |
| Keywords |
Alphavirus Infections/immunology; Alphavirus Infections/pathology; Alphavirus Infections/virology; Animals; Case-Control Studies; Chikungunya virus/immunology; Chikungunya virus/physiology; Cluster Analysis; Endoplasmic Reticulum/metabolism; Female; Foot/pathology; Foot/virology; Gene Expression Regulation/immunology; HEK293 Cells; Host-Pathogen Interactions; Humans; Immunity, Innate/genetics; Mice; Mice, Inbred C57BL; Monocytes/metabolism; Monocytes/virology; Protein Structure, Secondary; Protein Structure, Tertiary; Protein Transport; Proteins/genetics; Proteins/metabolism; Proteins/physiology; Statistics, Nonparametric; Transcriptome; Virus Replication |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0002230: positive regulation of defense response to virus by host |
ECO:0000314: |
P |
As seen in figure 7, researchers investigated whether loss of viperin expression affects type I IFN–mediated antiviral response by pretreating WT and Rsad2–/– fibroblasts with type I IFNs for 4 hours prior to CHIKV infection. Both IFN-α and IFN-β effectively inhibited CHIKV infection and replication to a comparable level in WT and Rsad2–/– fibroblasts, which demonstrated the importance of type I IFNs in limiting CHIKV infection. |
complete | ||||
| GO:0005783: endoplasmic reticulum |
ECO:0000314: |
C |
Fig.5 |
complete | ||||
|
part_of |
GO:0005783: endoplasmic reticulum |
ECO:0000314: direct assay evidence used in manual assertion |
C |
Seeded From UniProt |
complete | |||
| GO:0044165: host cell endoplasmic reticulum |
ECO:0000314: |
C |
Fig.5 |
complete | ||||
|
part_of |
GO:0044165: host cell endoplasmic reticulum |
ECO:0000314: direct assay evidence used in manual assertion |
C |
Seeded From UniProt |
complete | |||
See also
References
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