Lim Sora, Cha Seho, Jang Jun Hyeong, Yang Dahye, Choe Joonho, Seo Taegun
Department of Life Science, Dongguk University-Seoul, Goyang 10326, Republic of Korea.
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.
J Microbiol Biotechnol. 2017 Jan 28;27(1):189-196. doi: 10.4014/jmb.1607.07032.
Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with formation of Kaposi's sarcoma, multicentric Castleman's disease, and primary effusion lymphoma. Replication and transcription activator (RTA) genes are expressed upon reactivation of KSHV, which displays a biphasic life cycle consisting of latent and lytic replication phases. RTA protein expression results in KSHV genome amplification and successive viral lytic gene expression. Transcriptional activity of viral lytic genes is regulated through epigenetic modifications. In Raji cells latently infected with Epstein-Barr virus, various modifications, such as acetylation and methylation, have been identified at specific lysine residues in histone H4 during viral reactivation, supporting the theory that expression of specific lytic genes is controlled by histone modification processes. Data obtained from chromatin immunoprecipitation and quantitative real-time PCR analyses revealed alterations in the H4K8ac and H4K20me3 levels at lytic gene promoters during reactivation. Our results indicate that H4K20me3 is associated with the maintenance of latency, while H4K8ac contributes to KSHV reactivation in infected TREx BCBL-1 RTA cells.
卡波西肉瘤相关疱疹病毒（KSHV）与卡波西肉瘤、多中心性Castleman病和原发性渗出性淋巴瘤的形成有关。复制和转录激活因子（RTA）基因在KSHV重新激活时表达，KSHV呈现出由潜伏和裂解复制阶段组成的双相生命周期。RTA蛋白表达导致KSHV基因组扩增和后续病毒裂解基因表达。病毒裂解基因的转录活性通过表观遗传修饰来调节。在潜伏感染爱泼斯坦-巴尔病毒的Raji细胞中，在病毒重新激活过程中，已在组蛋白H4的特定赖氨酸残基处鉴定出各种修饰，如乙酰化和甲基化，这支持了特定裂解基因的表达受组蛋白修饰过程控制的理论。从染色质免疫沉淀和定量实时PCR分析获得的数据显示，重新激活期间裂解基因启动子处的H4K8ac和H4K20me3水平发生了变化。我们的结果表明，H4K20me3与潜伏期的维持有关，而H4K8ac有助于感染的TREx BCBL-1 RTA细胞中的KSHV重新激活。
