Department of Molecular Virology, Institute of Experimental Biology, A. Mickiewicz University, Umultowska 89, 61-614 Poznań, Poland.
Department of Molecular and Cellular Biology, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, Umultowska 89, 61-614 Poznań, Poland.
Mutat Res Rev Mutat Res. 2017 Apr-Jun;772:36-50. doi: 10.1016/j.mrrev.2016.09.006. Epub 2016 Sep 19.
Human Papillomaviruses (HPVs) are double-stranded DNA viruses, that infect epithelial cells and are etiologically involved in the development of human cancer. Today, over 200 types of human papillomaviruses are known. They are divided into low-risk and high-risk HPVs depending on their potential to induce carcinogenesis, driven by two major viral oncoproteins, E6 and E7. By interacting with cellular partners, these proteins are involved in interdependent viral and cell cycles in stratified differentiating epithelium, and concomitantly induce epigenetic changes in infected cells and those undergoing malignant transformation. E6 and E7 oncoproteins interact with and/or modulate expression of many proteins involved in epigenetic regulation, including DNA methyltransferases, histone-modifying enzymes and subunits of chromatin remodeling complexes, thereby influencing host cell transcription program. Furthermore, HPV oncoproteins modulate expression of cellular micro RNAs. Most of these epigenetic actions in a complex dynamic interplay participate in the maintenance of persistent infection, cell transformation, and development of invasive cancer by a considerable deregulation of tumor suppressor and oncogenes. In this study, we have undertaken to discuss a number of studies concerning epigenetic regulations in HPV-dependent cells and to focus on those that have biological relevance to cancer progression.
人乳头瘤病毒（HPV）是双链 DNA 病毒，感染上皮细胞，与人类癌症的发展有病因学关系。如今，已知有超过 200 种人乳头瘤病毒。根据其致癌潜能，它们分为低风险和高风险 HPV，主要由两种病毒致癌蛋白 E6 和 E7 驱动。这些蛋白通过与细胞伴侣相互作用，参与分层分化上皮中的相互依赖的病毒和细胞周期，并同时诱导受感染细胞和发生恶性转化的细胞中的表观遗传改变。E6 和 E7 致癌蛋白与参与表观遗传调控的许多蛋白相互作用和/或调节其表达，包括 DNA 甲基转移酶、组蛋白修饰酶和染色质重塑复合物的亚基，从而影响宿主细胞的转录程序。此外，HPV 致癌蛋白还调节细胞 microRNAs 的表达。这些表观遗传作用中的大多数在复杂的动态相互作用中参与持续感染的维持、细胞转化和侵袭性癌症的发展，导致肿瘤抑制基因和癌基因的显著失调。在这项研究中，我们讨论了一些关于 HPV 依赖性细胞中的表观遗传调控的研究，并重点关注那些与癌症进展具有生物学相关性的研究。
