Guion Lucile G, Sapp Martin
Department of Microbiology and Immunology, Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, LA, United States.
Feist Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA, United States.
Front Cell Infect Microbiol. 2020 Feb 19;10:35. doi: 10.3389/fcimb.2020.00035. eCollection 2020.
Promyelocytic leukemia (PML) nuclear bodies (NBs) are highly dynamic subnuclear structures. Their name giving major component, PML protein, is essential for their formation. PML is present in many different isoforms due to differential splicing, which seem to contribute differently to PML NBs function. Sp100 and DAXX are also permanently residing in these structures. PML NBs disassemble in mitosis to form large cytoplasmic aggregates and reassemble after completion of cell division. Posttranslational modifications such as SUMOylation play important roles for protein association with PML NBs. In addition to the factors permanently associated with PML NBs, a large number of proteins may transiently reside in PML NBs dependent on cell stage, type, and condition. PML NBs have been indirectly implicated in a large number of cellular processes including apoptosis, transcriptional regulation, DNA repair and replication. They are considered hot spots for posttranslational modifications and may serve as readily accessible protein depots. However, a precise function has been difficult to assign. Many DNA viruses target PML NBs after entry often resulting in reorganization of these subnuclear structures. Antiviral activity has been assigned to PML NBs partially based on the observation that PML protein is an interferon stimulated gene. In contrast, human papillomavirus (HPV) infection requires the presence of PML protein suggesting that PML NBs may be essential to establish infection. This review will summarize and discuss recent advances in our understanding of the role of PML NBs and individual protein components in the establishment of HPV infection.
早幼粒细胞白血病（PML）核体（NBs）是高度动态的亚核结构。其命名来源的主要成分PML蛋白，对其形成至关重要。由于可变剪接，PML存在多种不同的异构体，它们对PML NBs功能的贡献似乎有所不同。Sp100和DAXX也永久存在于这些结构中。PML NBs在有丝分裂时解体形成大的细胞质聚集体，并在细胞分裂完成后重新组装。翻译后修饰如SUMO化对于蛋白质与PML NBs的结合起重要作用。除了与PML NBs永久相关的因子外，大量蛋白质可能根据细胞阶段、类型和条件短暂存在于PML NBs中。PML NBs间接参与了大量细胞过程，包括细胞凋亡、转录调控、DNA修复和复制。它们被认为是翻译后修饰的热点，可能作为易于接近的蛋白质库。然而，其精确功能一直难以确定。许多DNA病毒进入细胞后靶向PML NBs，常常导致这些亚核结构的重组。抗病毒活性部分基于PML蛋白是一种干扰素刺激基因这一观察结果而归因于PML NBs。相反，人乳头瘤病毒（HPV）感染需要PML蛋白的存在，这表明PML NBs可能对建立感染至关重要。本综述将总结并讨论我们对PML NBs及单个蛋白质成分在HPV感染建立中的作用的理解的最新进展。
