McNally Beth A, Trgovcich Joanne, Maul Gerd G, Liu Yang, Zheng Pan
Division of Cancer Immunology, Department of Pathology, The Ohio State University Medical Center, Columbus, Ohio, United States of America.
PLoS One. 2008 May 28;3(5):e2277. doi: 10.1371/journal.pone.0002277.
PML gene was discovered as a fusion partner with retinoic acid receptor (RAR) alpha in the t(15:17) chromosomal translocation associated with acute promyelocytic leukemia (APL). Nuclear PML protein has been implicated in cell growth, tumor suppression, apoptosis, transcriptional regulation, chromatin remodeling, DNA repair, and anti-viral defense. The localization pattern of promyelocytic leukemia (PML) protein is drastically altered during viral infection. This alteration is traditionally viewed as a viral strategy to promote viral replication. Although multiple PML splice variants exist, we demonstrate that the ratio of a subset of cytoplasmic PML isoforms lacking exons 5 & 6 is enriched in cells exposed to herpes simplex virus-1 (HSV-1). In particular, we demonstrate that a PML isoform lacking exons 5 & 6, called PML Ib, mediates the intrinsic cellular defense against HSV-1 via the cytoplasmic sequestration of the infected cell protein (ICP) 0 of HSV-1. The results herein highlight the importance of cytoplasmic PML and call for an alternative, although not necessarily exclusive, interpretation regarding the redistribution of PML that is seen in virally infected cells.
早幼粒细胞白血病（PML）基因是在与急性早幼粒细胞白血病（APL）相关的t(15;17)染色体易位中作为维甲酸受体（RAR）α的融合伴侣被发现的。核PML蛋白与细胞生长、肿瘤抑制、细胞凋亡、转录调控、染色质重塑、DNA修复及抗病毒防御有关。在病毒感染期间，早幼粒细胞白血病（PML）蛋白的定位模式会发生剧烈改变。传统上，这种改变被视为病毒促进自身复制的一种策略。尽管存在多种PML剪接变体，但我们证明，在暴露于单纯疱疹病毒1型（HSV-1）的细胞中，缺乏外显子5和6的细胞质PML亚型子集的比例有所增加。特别是，我们证明了一种缺乏外显子5和6的PML亚型，称为PML Ib，通过对HSV-1感染细胞蛋白（ICP）0进行细胞质隔离来介导细胞对HSV-1的固有防御。本文的结果突出了细胞质PML的重要性，并呼吁对病毒感染细胞中出现的PML重新分布作出另一种解释，尽管不一定是唯一的解释。
