Human Cytomegalovirus Directly Induces the Antiviral Protein Viperin to Enhance Infectivity
Human Cytomegalovirus Directly Induces the Antiviral Protein Viperin to Enhance Infectivity
复制标题
DOI：
10.1126/science.1202007
复制
发表时间：
2011-05-27
期刊：
影响因子：
56.9
通讯作者：
Cresswell, Peter
中科院分区：
文献类型：
--
作者：
Seo, Jun-Young;Yaneva, Rakina;Cresswell, Peter
蝰蛇蛋白是一种干扰素诱导的蛋白质，其通过人巨细胞病毒（HCMV）感染在细胞中直接诱导。为什么HCMV会诱导具有抗病毒活性的蝰蛇蛋白，目前还不清楚。我们表明，HCMV诱导的蝰蛇蛋白破坏细胞代谢，以提高感染过程。蝰蛇蛋白与病毒蛋白vMIA的相互作用导致蝰蛇蛋白从内质网重新定位到线粒体。在那里，蝰蛇蛋白与线粒体三功能蛋白相互作用，介导脂肪酸的β-氧化产生三磷酸腺苷（ATP）。这种相互作用与蝰蛇蛋白，但不是与突变缺乏蝰蛇蛋白铁硫簇结合基序，减少细胞ATP的产生，这导致肌动蛋白细胞骨架破坏和增强感染。以前被认为是vMIA的viperin的这种功能表明HCMV已经吸收了viperin来促进感染过程。
Viperin is an interferon-inducible protein that is directly induced in cells by human cytomegalovirus (HCMV) infection. Why HCMV would induce viperin, which has antiviral activity, is unknown. We show that HCMV-induced viperin disrupts cellular metabolism to enhance the infectious process. Viperin interaction with the viral protein vMIA resulted in viperin relocalization from the endoplasmic reticulum to the mitochondria. There, viperin interacted with the mitochondrial trifunctional protein that mediates beta-oxidation of fatty acids to generate adenosine triphosphate (ATP). This interaction with viperin, but not with a mutant lacking the viperin iron-sulfur cluster-binding motif, reduced cellular ATP generation, which resulted in actin cytoskeleton disruption and enhancement of infection. This function of viperin, which was previously attributed to vMIA, suggests that HCMV has coopted viperin to facilitate the infectious process.