Heinrich-Pette-Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
Semin Immunopathol. 2020 Apr;42(2):143-157. doi: 10.1007/s00281-020-00787-z. Epub 2020 Mar 26.
Kaposi sarcoma-associated herpesvirus (KSHV) is the etiologic agent of several malignancies of endothelial and B-cell origin. The fact that latently infected tumor cells in these malignancies do not express classical viral oncogenes suggests that pathogenesis of KSHV-associated disease results from multistep processes that, in addition to constitutive viral gene expression, may require accumulation of cellular alterations. Heritable changes of the epigenome have emerged as an important co-factor that contributes to the pathogenesis of many non-viral cancers. Since KSHV encodes a number of factors that directly or indirectly manipulate host cell chromatin, it is an intriguing possibility that epigenetic reprogramming also contributes to the pathogenesis of KSHV-associated tumors. The fact that heritable histone modifications have also been shown to regulate viral gene expression programs in KSHV-infected tumor cells underlines the importance of epigenetic control during latency and tumorigenesis. We here review what is presently known about the role of epigenetic regulation of viral and host chromatin in KSHV infection and discuss how viral manipulation of these processes may contribute to the development of KSHV-associated disease.
卡波西肉瘤相关疱疹病毒（KSHV）是几种内皮和 B 细胞来源的恶性肿瘤的病原体。事实上，这些恶性肿瘤中潜伏感染的肿瘤细胞不表达经典的病毒癌基因，这表明 KSHV 相关疾病的发病机制是由多步骤过程引起的，除了组成性病毒基因表达外，还可能需要细胞改变的积累。表观基因组的遗传性变化已成为导致许多非病毒癌症发病的重要协同因素。由于 KSHV 编码了许多直接或间接操纵宿主细胞染色质的因子，因此表观遗传重编程也有助于 KSHV 相关肿瘤的发病机制，这是一个有趣的可能性。事实上，在 KSHV 感染的肿瘤细胞中，可遗传的组蛋白修饰也被证明可以调节病毒基因表达程序，这突出了在潜伏期和肿瘤发生过程中表观遗传控制的重要性。我们在这里回顾了目前已知的表观遗传调节病毒和宿主染色质在 KSHV 感染中的作用，并讨论了病毒对这些过程的操纵如何有助于 KSHV 相关疾病的发展。
