Pantry Shara N, Medveczky Peter G
Department of Molecular Medicine, College of Medicine, University of South Florida, 12901 Bruce B. Downs Boulevard, MDC7, Tampa, FL 33612, USA.
Semin Cancer Biol. 2009 Jun;19(3):153-7. doi: 10.1016/j.semcancer.2009.02.010. Epub 2009 Feb 21.
Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi's sarcoma and B-lymphocyte disorders, primary effusion lymphoma (PEL) and Multicentric Castleman's Disease (MCD). KSHV usually exists in a latent form in which the viral genome is circularized into an extrachormosomal episome. However, induction of lytic replication by environmental stimuli or chemical agents is important for the spread of KSHV. The switch between latency and lytic replication is regulated by epigenetic factors. Hypomethylation of the promoter of replication and transcription activator (RTA), which is essential for the lytic switch, leads to KSHV reactivation. Histone acetylation induces KSHV replication by influencing protein-protein-associations and transcription factor binding. Histone modifications also determine chromatin structure and nucleosome positioning, which are important for KSHV DNA replication during latency. The association of KSHV proteins with chromatin remodeling complexes promotes the open chromatin structure needed for transcription factor binding and DNA replication. Additionally, post-translational modification of KSHV proteins is important for the regulation of RTA activity and KSHV replication. KSHV may also cause epigenetic modification of the host genome, contributing to promoter hypermethylation of tumor suppressor genes in KSHV-associated neoplasias.
卡波西肉瘤相关疱疹病毒（KSHV）是卡波西肉瘤、B淋巴细胞疾病、原发性渗出性淋巴瘤（PEL）和多中心性卡斯特曼病（MCD）的病原体。KSHV通常以潜伏形式存在，其中病毒基因组环化形成一个染色体外附加体。然而，环境刺激或化学试剂诱导的裂解复制对于KSHV的传播很重要。潜伏与裂解复制之间的转换受表观遗传因素调控。复制和转录激活因子（RTA）启动子的低甲基化对裂解转换至关重要，可导致KSHV重新激活。组蛋白乙酰化通过影响蛋白质-蛋白质相互作用和转录因子结合来诱导KSHV复制。组蛋白修饰还决定染色质结构和核小体定位，这对潜伏期间KSHV DNA复制很重要。KSHV蛋白与染色质重塑复合物的结合促进了转录因子结合和DNA复制所需的开放染色质结构。此外，KSHV蛋白的翻译后修饰对RTA活性和KSHV复制的调控很重要。KSHV还可能导致宿主基因组的表观遗传修饰，促成KSHV相关肿瘤中肿瘤抑制基因的启动子高甲基化。
