Viperin (cig5), an IFN-inducible antiviral protein directly induced by human cytomegalovirus
Viperin (cig5), an IFN-inducible antiviral protein directly induced by human cytomegalovirus
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DOI：
10.1073/pnas.011593298
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发表时间：
2001-12-18
影响因子：
11.1
通讯作者：
Cresswell, P
中科院分区：
文献类型：
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作者：
Chin, KC;Cresswell, P
干扰素抑制人巨细胞病毒（HCMV）复制的机制知之甚少。事实上，HCMV感染成纤维细胞启动了I型IFN诱导基因的一个子集的表达，其在感染过程中的作用尚不清楚。我们在这里描述了一种细胞质抗病毒蛋白的鉴定，该蛋白由IFN、HCMV感染和HCMV包膜蛋白糖蛋白B（gB）诱导。该蛋白在成纤维细胞中的稳定表达抑制了生产性HCMV感染，下调了已知对于病毒组装和成熟不可或缺的几种HCMV结构蛋白（gB、pp28和pp65）。我们将这种蛋白质命名为viperin（病毒抑制蛋白，内质网相关，干扰素诱导）。HCMV感染导致诱导的蝰蛇蛋白从其正常的内质网协会的重新分配，首先到高尔基体，然后到含有gB和pp28的细胞质空泡。HCMV感染前的表达减少了蝰蛇蛋白从内质网到高尔基体的再分布，并阻止了空泡定位，这可能反映了HCMV逃避抗病毒功能的机制。
Little is known about the mechanism by which IFNs inhibit human cytomegalovirus (HCMV) replication. Indeed, infection of fibroblasts with HCMV initiates the expression of a subset of type I IFN-inducible genes whose role in the infectious process is unclear. We describe here the identification of a cytoplasmic antiviral protein that is induced by IFNs, by HCMV infection, and by the HCMV envelope protein, glycoprotein B (gB). Stable expression of the protein in fibroblasts inhibits productive HCMV infection, down-regulating several HCMV structural proteins (gB, pp28, and pp65) known to be indispensable for viral assembly and maturation. We have named the protein viperin (for virus inhibitory protein, endoplasmic reticulum-associated, interferon-inducible). HCMV infection causes the redistribution of the induced viperin from its normal endoplasmic reticulum association, first to the Golgi apparatus and then to cytoplasmic vacuoles containing gB and pp28. Expression before HCMV infection reduces viperin redistribution from the endoplasmic reticulum to the Golgi apparatus and prevents vacuolar localization, perhaps reflecting the mechanism used by HCMV to evade the antiviral function.