Viperin restricts chikungunya virus replication and pathology
Terk-Shin Teng, … , Keh-Chuang Chin, Lisa F.P. Ng
Terk-Shin Teng, … , Keh-Chuang Chin, Lisa F.P. Ng
Published November 19, 2012
Citation Information: J Clin Invest. 2012;122(12):4447-4460. https://doi.org/10.1172/JCI63120.
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Research Article Virology

Viperin restricts chikungunya virus replication and pathology

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.

Authors

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

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Figure 1

Expression profiles of type I IFNs and related ISGs in CHIKV-infected patients.

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Expression profiles of type I IFNs and related ISGs in CHIKV-infected pa...
(A) Expression profiles of type I IFNs and related ISGs in PBMCs of CHIKV-infected patients (n = 24) at various time points of the disease were analyzed by qRT-PCR. Data were normalized to GAPDH and presented as expression relative to the mean of healthy controls (n = 10). Data are presented by 2-way hierarchical clustering after dividing the patient cohort according to viral load levels into HVL (n = 11) and LVL (n = 13) groups. Each colored well in the 4 heatmaps represents the relative levels of expression of a particular gene (green, low expression; red, high expression). The different phases of the disease are defined as acute phase (median 4 days post illness onset), early convalescent phase (median 10 days post illness onset), late convalescent phase (4–6 weeks post illness onset) and chronic phase (2–3 months post illness onset). (B) Viral load influenced induction of the innate immune response. The relative expression of the indicated genes was compared between HVL and LVL groups during the acute phase of disease at median 4 days post illness onset. Data are mean ± SEM. **P < 0.01, ***P < 0.001, Mann-Whitney U test.