Division of Infection and Immunity, The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK.
Division of Infection and Immunity, The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK
Open Biol. 2017 Nov;7(11). doi: 10.1098/rsob.160298.
Successful generation of virions from infected cells is a complex process requiring orchestrated regulation of host and viral genes. Cells infected with human cytomegalovirus (HCMV) undergo a dramatic reorganization of membrane organelles resulting in the formation of the virion assembly compartment, a process that is not fully understood. Here we show that acidification of vacuoles by the cellular v-ATPase is a crucial step in the formation of the virion assembly compartment and disruption of acidification results in mis-localization of virion components and a profound reduction in infectious virus levels. In addition, knockdown of ATP6V0C blocks the increase in nuclear size, normally associated with HCMV infection. Inhibition of the v-ATPase does not affect intracellular levels of viral DNA synthesis or gene expression, consistent with a defect in assembly and egress. These studies identify a novel host factor involved in virion production and a potential target for antiviral therapy.
成功地从受感染的细胞中产生病毒粒子是一个复杂的过程，需要宿主和病毒基因的协调调控。感染人巨细胞病毒（HCMV）的细胞经历了膜细胞器的剧烈重排，导致病毒装配隔室的形成，这一过程尚不完全清楚。在这里，我们表明细胞 v-ATPase 的酸化是病毒装配隔室形成的关键步骤，酸化的破坏导致病毒粒子成分的错误定位和感染性病毒水平的显著降低。此外，ATP6V0C 的敲低会阻止与 HCMV 感染相关的核大小的增加。v-ATPase 的抑制不影响病毒 DNA 合成或基因表达的细胞内水平，这与装配和出芽的缺陷一致。这些研究确定了一种参与病毒粒子产生的新的宿主因子，也是抗病毒治疗的一个潜在靶点。
