Di Domenico Enea Gino, Toma Luigi, Bordignon Valentina, Trento Elisabetta, D'Agosto Giovanna, Cordiali-Fei Paola, Ensoli Fabrizio
Clinical Pathology and Microbiology Department, San Gallicano Institute, IRCCS, Rome 00144, Italy.
Infectious Disease Consultant, San Gallicano Institute, IRCCS, Rome 00144, Italy.
Int J Mol Sci. 2016 Jun 1;17(6):854. doi: 10.3390/ijms17060854.
The human herpes virus 8 (HHV-8), also known as Kaposi sarcoma-associated herpes virus (KSHV), can infect endothelial cells often leading to cell transformation and to the development of tumors, namely Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and the plasmablastic variant of multicentric Castleman's disease. KSHV is prevalent in areas such as sub-Saharan Africa and the Mediterranean region presenting distinct genotypes, which appear to be associated with differences in disease manifestation, according to geographical areas. In infected cells, KSHV persists in a latent episomal form. However, in a limited number of cells, it undergoes spontaneous lytic reactivation to ensure the production of new virions. During both the latent and the lytic cycle, KSHV is programmed to express genes which selectively modulate the DNA damage response (DDR) through the activation of the ataxia telangiectasia mutated (ATM) pathway and by phosphorylating factors associated with the DDR, including the major tumor suppressor protein p53 tumor suppressor p53. This review will focus on the interplay between the KSHV and the DDR response pathway throughout the viral lifecycle, exploring the putative molecular mechanism/s that may contribute to malignant transformation of host cells.
人类疱疹病毒8型（HHV-8），也称为卡波西肉瘤相关疱疹病毒（KSHV），可感染内皮细胞，常导致细胞转化并引发肿瘤，即卡波西肉瘤（KS）、原发性渗出性淋巴瘤（PEL）以及多中心Castleman病的浆母细胞变异型。KSHV在撒哈拉以南非洲和地中海地区等流行，呈现出不同的基因型，根据地理区域的不同，这些基因型似乎与疾病表现的差异有关。在受感染的细胞中，KSHV以潜伏的游离形式持续存在。然而，在少数细胞中，它会发生自发的裂解再激活，以确保产生新的病毒粒子。在潜伏和裂解周期中，KSHV都会被编程表达基因，这些基因通过激活共济失调毛细血管扩张突变（ATM）途径以及磷酸化与DNA损伤反应（DDR）相关的因子，包括主要的肿瘤抑制蛋白p53，来选择性地调节DNA损伤反应（DDR）。本综述将重点关注KSHV与DDR反应途径在整个病毒生命周期中的相互作用，探讨可能导致宿主细胞恶性转化的假定分子机制。
