Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, New Jersey, USA.
mBio. 2010 Nov 30;1(5):e00282-10. doi: 10.1128/mBio.00282-10.
The human cytomegalovirus virion is composed of a DNA genome packaged in an icosahedral capsid, surrounded by a tegument of protein and RNA, all enclosed within a glycoprotein-studded envelope. Achieving this intricate virion architecture requires a coordinated process of assembly and egress. We show here that pUL71, a component of the virion tegument with a previously uncharacterized function, is required for the virus-induced reorganization of host cell membranes, which is necessary for efficient viral assembly and egress. A mutant that did not express pUL71 was able to efficiently accumulate viral genomes and proteins that were tested but was defective for the production and release of infectious virions. The protein localized to vesicular structures at the periphery of the viral assembly compartment, and during infection with a pUL71-deficient virus, these structures were grossly enlarged and aberrantly contained a cellular marker of late endosomes/lysosomes. Mutant virus preparations exhibited less infectivity per unit genome than wild-type virus preparations, due to aggregation of virus particles and their association with membrane fragments. Finally, mutant virus particles accumulated within the cytoplasm of infected cells and were localized to the periphery of large structures with properties of lysosomes, whose formation was kinetically favored in mutant-virus-infected cells. Together, these observations point to a role for pUL71 in the establishment and/or maintenance of a functional viral assembly compartment that is required for normal virion trafficking and egress from infected cells.
人类巨细胞病毒病毒粒子由包裹在二十面体衣壳内的 DNA 基因组组成，衣壳周围是一层蛋白质和 RNA 组成的被膜，所有这些都被糖蛋白覆盖的包膜所包围。实现这种复杂的病毒粒子结构需要一个协调的组装和出芽过程。我们在这里表明，pUL71 是病毒被膜的一个组成部分，具有以前未被描述的功能，它是病毒诱导的宿主细胞膜重排所必需的，这对于有效的病毒组装和出芽是必要的。一个不能表达 pUL71 的突变体能够有效地积累病毒基因组和蛋白质，但不能产生和释放有感染力的病毒粒子。该蛋白定位于病毒组装隔室边缘的囊泡结构中，在感染 pUL71 缺陷病毒时，这些结构明显增大，并异常包含晚期内体/溶酶体的一种细胞标记物。突变病毒制剂的感染性比野生型病毒制剂每单位基因组的感染性低，这是由于病毒粒子的聚集及其与膜片段的关联。最后，突变病毒粒子在感染细胞的细胞质中积累，并定位于具有溶酶体特性的大结构的外围，在突变病毒感染的细胞中，这些结构的形成在动力学上是有利的。总之，这些观察结果表明 pUL71 在建立和/或维持功能性病毒组装隔室中发挥作用，这对于正常的病毒粒子运输和从感染细胞中出芽是必需的。
