A role for cytoplasmic PML in cellular resistance to viral infection.
A role for cytoplasmic PML in cellular resistance to viral infection.
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DOI：
10.1371/journal.pone.0002277
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发表时间：
2008-05-28
期刊：
影响因子：
3.7
通讯作者：
Zheng, Pan
中科院分区：
文献类型：
--
作者：
McNally, Beth A.;Trgovcich, Joanne;Maul, Gerd G.;Liu, Yang;Zheng, Pan
在急性早幼粒细胞白血病t(15：17)染色体易位中，发现pML基因与维甲酸受体α融合。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修复和抗病毒防御有关。在病毒感染过程中，早幼粒细胞白血病(PML)蛋白的定位模式发生了很大的变化。这种改变传统上被视为一种促进病毒复制的病毒策略。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(HSV-1)的细胞中，缺乏外显子5和6的细胞质PML亚型的比例较高。特别是，我们证明了缺少外显子5和6的PML亚型，称为PML Ib，通过胞质隔离HSV-1的感染细胞蛋白(ICP0)来介导对HSV-1的内在细胞防御。这里的结果强调了细胞质PML的重要性，并呼吁对病毒感染细胞中PML的重新分布做出另一种尽管不一定是排他性的解释。
PML gene was discovered as a fusion partner with retinoic acid receptor (RAR) α 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.
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