Viperin inhibits hepatitis C virus replication by interfering with binding of NS5A to host protein hVAP-33

Wang, Shanshan; Wu, Xianfang; Pan, Tingting; Song, Wuhui; Wang, Yaohui; Zhang, Fei; Yuan, Zhenghong

doi:10.1099/vir.0.033860-0

Cited by 101 publications

(125 citation statements)

References 32 publications

Supporting

Mentioning

120

Contrasting

Order By: Relevance

“…The C-terminus rather than the SAM domains of viperin were essential for its antiviral effect. 23,45 Viperin appears to inhibit replication of other viruses by at least 2 different mechanisms. First, in influenza virus-infected murine macrophages, viperin interacts with and inhibits FPPS, an enzyme involved in the synthesis of multiple isoprenoid-derived lipids.…”

Section: Discussionmentioning

confidence: 99%

HIV-1 infection of human macrophages directly induces viperin which inhibits viral production

Nasr

Maddocks

Turville

et al. 2012

Blood

187

198

View full text Add to dashboard Cite

AbstractMacrophages are key target cells for HIV-1. HIV-1BaL induced a subset of interferon-stimulated genes in monocyte-derived macrophages (MDMs), which differed from that in monocyte-derived dendritic cells and CD4 T cells, without inducing any interferons. Inhibition of type I interferon induction was mediated by HIV-1 inhibition of interferon-regulated factor (IRF3) nuclear translocation. In MDMs, viperin was the most up-regulated interferon-stimulated genes, and it significantly inhibited HIV-1 production. HIV-1 infection disrupted lipid rafts via viperin induction and redistributed viperin to CD81 compartments, the site of HIV-1 egress by budding in MDMs. Exogenous farnesol, which enhances membrane protein prenylation, reversed viperin-mediated inhibition of HIV-1 production. Mutagenesis analysis in transfected cell lines showed that the internal S-adenosyl methionine domains of viperin were essential for its antiviral activity. Thus viperin may contribute to persistent noncytopathic HIV-1 infection of macrophages and possibly to biologic differences with HIV-1–infected T cells.

show abstract

Section: Discussionmentioning

confidence: 99%

HIV-1 infection of human macrophages directly induces viperin which inhibits viral production

Nasr

Maddocks

Turville

et al. 2012

Blood

187

198

View full text Add to dashboard Cite

show abstract

“…Interestingly, RSAD2, an ISG with a broad spectrum of antiviral functions (28)(29)(30)(31)(39)(40)(41), was also significantly induced during CHIKV infection ( Figure 1A and Supplemental Figure 1). Expression of IFNA, IFNB, IRF7, RSAD2, ISG15, ISG54, ISG56, RIG-I, MDA5, and PKR generally peaked during the acute phase of the disease and was sustained to the early convalescent phase (median…”

Section: Figurementioning

confidence: 99%

Viperin restricts chikungunya virus replication and pathology

Teng¹,

Foo²,

Simamarta³

et al. 2012

J. Clin. Invest.

162

194

View full text Add to dashboard Cite

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.

show abstract

“…Viperin also associates with lipid droplets (16), vital components in the hepatitis C virus (HCV) life cycle. Viperin appears to disrupt the formation of the HCV replication complex on lipid droplets by its interaction with hVAP-33 (vesicle-associated membrane protein-associated protein of 33 kDa), which interferes with binding of the viral NS5A protein to hVAP-33 (15,45). Besides being induced by IFN, viperin expression is also induced following virus infection, and viperin actually aids HCMV replication in fibroblasts (41).…”

Section: Discussionmentioning

confidence: 99%

Viperin, MTAP44, and Protein Kinase R Contribute to the Interferon-Induced Inhibition of Bunyamwera Orthobunyavirus Replication

Carlton-Smith

Elliott

2012

J Virol

View full text Add to dashboard Cite

The first line of defense against viral infection is the interferon (IFN) response, which culminates in the expression of hundreds of proteins with presumed antiviral activity, and must be overcome by a virus for successful replication. The nonstructural NSs protein is the primary IFN antagonist encoded by Bunyamwera virus (BUNV), the prototype of the Orthobunyavirus genus and the family Bunyaviridae. The NSs protein interferes with RNA polymerase II-mediated transcription, thereby inhibiting cellular mRNA production, including IFN mRNAs. A recombinant virus, rBUNdelNSs, that is unable to express the NSs protein does not inhibit cellular transcription and is a strong IFN inducer. We report here that cells stimulated into the antiviral state by IFN-␤ treatment were protected against wild-type BUNV and rBUNdelNSs infection but addition of IFN-␤ after infection had little effect on the replication cycle of either virus. By screening a panel of cell lines that overexpressed individual IFN-stimulated genes, we found that protein kinase R (PKR), MTAP44, and particularly viperin appreciably restricted BUNV replication. The enzymatic activities of PKR and viperin were required for their inhibitory activities. Taken together, our data show that the restriction of BUNV replication mediated by IFN is an accumulated effect of at least three IFN-stimulated genes that probably act on different stages of the viral replication cycle.

show abstract

Viperin inhibits hepatitis C virus replication by interfering with binding of NS5A to host protein hVAP-33

Cited by 101 publications

References 32 publications

HIV-1 infection of human macrophages directly induces viperin which inhibits viral production

HIV-1 infection of human macrophages directly induces viperin which inhibits viral production

Viperin restricts chikungunya virus replication and pathology

Viperin, MTAP44, and Protein Kinase R Contribute to the Interferon-Induced Inhibition of Bunyamwera Orthobunyavirus Replication

Contact Info

Product

Resources

About