Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Viruses. 2020 Sep 17;12(9):1034. doi: 10.3390/v12091034.
Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with three malignancies- Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman's disease (MCD). Central to the pathogenesis of these diseases is the KSHV viral life cycle, which is composed of a quiescent latent phase and a replicative lytic phase. While the establishment of latency enables persistent KSHV infection and evasion of the host immune system, lytic replication is essential for the dissemination of the virus between hosts and within the host itself. The transition between these phases, known as lytic reactivation, is controlled by a complex set of environmental, host, and viral factors. The effects of these various factors converge on the regulation of two KSHV proteins whose functions facilitate each phase of the viral life cycle-latency-associated nuclear antigen (LANA) and the master switch of KSHV reactivation, replication and transcription activator (RTA). This review presents the current understanding of how the transition between the phases of the KSHV life cycle is regulated, how the various phases contribute to KSHV pathogenesis, and how the viral life cycle can be exploited as a therapeutic target.
卡波氏肉瘤相关疱疹病毒（KSHV）与三种恶性肿瘤相关 - 卡波氏肉瘤（KS）、原发性渗出性淋巴瘤（PEL）和多中心卡斯特曼病（MCD）。这些疾病发病机制的核心是 KSHV 病毒生命周期，它由静止潜伏期和复制裂解期组成。虽然潜伏期的建立使 KSHV 持续感染并逃避宿主免疫系统，但裂解复制对于病毒在宿主之间和宿主自身内部的传播至关重要。这些阶段之间的转换，称为裂解再激活，由一系列复杂的环境、宿主和病毒因素控制。这些各种因素的影响集中在调节两种 KSHV 蛋白上，其功能促进病毒生命周期的每个阶段 - 潜伏相关核抗原（LANA）和 KSHV 再激活、复制和转录激活剂（RTA）的主开关。这篇综述介绍了目前对 KSHV 生命周期各阶段之间的转换如何受到调节的理解，以及各阶段如何促进 KSHV 发病机制，以及如何将病毒生命周期作为治疗靶点加以利用。
