Nakahara Tomomi, Lambert Paul F
McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health, 1400 University Ave., Madison, WI 53706, USA.
Virology. 2007 Sep 30;366(2):316-29. doi: 10.1016/j.virol.2007.04.032. Epub 2007 Jun 1.
Promyelocytic leukemia oncogenic domains (PODs), also called nuclear domain 10 (ND10), are subnuclear structures that have been implicated in a variety of cellular processes as well as the life cycle of DNA viruses including papillomaviruses. In order to investigate the interplay between papillomaviruses and PODs, we analyzed the status of PODs in organotypic raft cultures of human keratinocytes harboring HPV genome that support the differentiation-dependent HPV life cycle. The number of PODs per nucleus was increased in the presence of HPV genomes selectively within the poorly differentiated layers but was absent in the terminally differentiated layers of the stratified epithelium. This increase in PODs was correlated with an increase in abundance of post-translationally modified PML protein. Neither the E2-dependent transcription nor viral DNA replication was reliant upon the presence of PML. Implications of these findings in terms of HPV's interaction with its host are discussed.
早幼粒细胞白血病致癌结构域(PODs),也称为核结构域10(ND10),是一种亚核结构,与多种细胞过程以及包括乳头瘤病毒在内的DNA病毒的生命周期有关。为了研究乳头瘤病毒与PODs之间的相互作用,我们分析了携带支持依赖分化的HPV生命周期的HPV基因组的人角质形成细胞的器官型筏培养物中PODs的状态。在分层上皮的未分化层中,选择性地存在HPV基因组的情况下,每个细胞核中PODs的数量增加,但在终末分化层中不存在。PODs的这种增加与翻译后修饰的PML蛋白丰度的增加相关。依赖E2的转录和病毒DNA复制均不依赖于PML的存在。讨论了这些发现对HPV与其宿主相互作用的意义。