Viperin (cig5), an IFN-inducible antiviral protein directly induced by human cytomegalovirus

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.

目前学界对于干扰素 (IFNs) 抑制人巨细胞病毒 (human cytomegalovirus, HCMV) 复制的具体机制仍知之甚少。事实上，人巨细胞病毒感染成纤维细胞后，会启动一组I型干扰素诱导基因的表达，但其在感染过程中的具体作用尚不明确。本研究报道了一种胞质抗病毒蛋白的鉴定结果：该蛋白可被干扰素 (IFNs)、人巨细胞病毒感染，以及人巨细胞病毒包膜糖蛋白B (glycoprotein B, gB) 诱导表达。在成纤维细胞中稳定表达该蛋白，可抑制人巨细胞病毒的增殖性感染，并下调数种已知对病毒组装与成熟不可或缺的人巨细胞病毒结构蛋白 (gB、pp28与pp65) 的表达。我们将该蛋白命名为viperin (virus inhibitory protein, endoplasmic reticulum-associated, interferon-inducible，即病毒抑制蛋白、内质网相关、干扰素诱导蛋白)。人巨细胞病毒感染会诱导viperin从其正常定位的内质网发生重分布：首先转移至高尔基体，随后进入包裹有gB与pp28的胞质空泡中。在人巨细胞病毒感染前预先表达viperin，可减少其从内质网向高尔基体的重分布，并阻止其定位于空泡中，这或许反映了人巨细胞病毒逃逸抗病毒功能的具体机制。