The interferon-inducible protein viperin inhibits influenza virus release by perturbing lipid rafts

被引:408
作者
Wang, Xiuyan
Hinson, Ella R.
Cresswell, Peter
机构
[1] Yale Univ, Sch Med, Dept Immunol, New Haven, CT 06520 USA
[2] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06520 USA
关键词
D O I
10.1016/j.chom.2007.06.009
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Interferons initiate the host antiviral response by inducing a number of genes, most with no defined antiviral function. Here we show that the interferon-induced protein viperin inhibits influenza A virus release from the plasma membrane of infected cells. Viperin expression altered plasma membrane fluidity by affecting the formation of lipid rafts, which are detergent-resistant membrane microdomains known to be the sites of influenza virus budding. Intracellular interaction of viperin with farnesyl diphosphate synthase (FPPS), an enzyme essential for isoprenoid biosynthesis, decreased the activity of the enzyme. Overexpression of FPPS reversed viperin-mediated inhibition of virus production and restored normal membrane fluidity, and reduction of FPPS levels by siRNA inhibited virus release and replication, indicating that the FPPS interaction underlies viperin's effects. These findings suggest that targeting the release stage of the life cycle may affect the replication of many enveloped viruses. Furthermore, FPPS may be an attractive target for antiviral therapy.
引用
收藏
页码:96 / 105
页数:10
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