Salsman Jayme, Zimmerman Nicole, Chen Tricia, Domagala Megan, Frappier Lori
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
PLoS Pathog. 2008 Jul 11;4(7):e1000100. doi: 10.1371/journal.ppat.1000100.
Herpesviruses are large, ubiquitous DNA viruses with complex host interactions, yet many of the proteins encoded by these viruses have not been functionally characterized. As a first step in functional characterization, we determined the subcellular localization of 234 epitope-tagged proteins from herpes simplex virus, cytomegalovirus, and Epstein-Barr virus. Twenty-four of the 93 proteins with nuclear localization formed subnuclear structures. Twelve of these localized to the nucleolus, and five at least partially localized with promyelocytic leukemia (PML) bodies, which are known to suppress viral lytic infection. In addition, two proteins disrupted Cajal bodies, and 19 of the nuclear proteins significantly decreased the number of PML bodies per cell, including six that were shown to be SUMO-modified. These results have provided the first functional insights into over 120 previously unstudied proteins and suggest that herpesviruses employ multiple strategies for manipulating nuclear bodies that control key cellular processes.
疱疹病毒是大型的、广泛存在的DNA病毒，与宿主有着复杂的相互作用，但这些病毒编码的许多蛋白质尚未进行功能表征。作为功能表征的第一步，我们确定了来自单纯疱疹病毒、巨细胞病毒和EB病毒的234种表位标记蛋白的亚细胞定位。93种具有核定位的蛋白中有24种形成了亚核结构。其中12种定位于核仁，5种至少部分定位于早幼粒细胞白血病（PML）小体，已知PML小体可抑制病毒的裂解感染。此外，两种蛋白破坏了卡哈尔体，19种核蛋白显著减少了每个细胞中PML小体的数量，其中6种被证明是SUMO修饰的。这些结果为120多种以前未研究过的蛋白质提供了首次功能见解，并表明疱疹病毒采用多种策略来操纵控制关键细胞过程的核小体。
