DeCotiis Jennifer L, Lukac David M
Department of Microbiology, Biochemistry, and Molecular Genetics, and Rutgers School of Graduate Studies, Rutgers Biomedical and Health Sciences, Rutgers University, New Jersey Medical School, 225 Warren St., ICPH E 350 C, Newark, NJ 07103, USA.
Pathogens. 2017 Aug 4;6(3):34. doi: 10.3390/pathogens6030034.
Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of two human cancers, Kaposi's Sarcoma (KS) and primary effusion lymphoma (PEL), and a lymphoproliferation, Multicentric Castleman's Disease (MCD). Progression to tumor development in KS is dependent upon the reactivation of the virus from its latent state. We, and others, have shown that the Replication and transcriptional activator (Rta) protein is the only viral gene product that is necessary and sufficient for viral reactivation. To induce the reactivation and transcription of viral genes, Rta forms a complex with the cellular DNA binding component of the canonical Notch signaling pathway, recombination signal binding protein for Jk (RBP-Jk). Formation of this Rta:RBP-Jk complex is necessary for viral reactivation to occur. Expression of activated Notch has been shown to be dysregulated in KSHV infected cells and to be necessary for cell growth and disease progression. Studies into the involvement of activated Notch in viral reactivation have yielded varied results. In this paper, we review the current literature regarding Notch dysregulation by KSHV and its role in viral infection and cellular pathogenesis.
卡波西肉瘤相关疱疹病毒（KSHV）是两种人类癌症——卡波西肉瘤（KS）和原发性渗出性淋巴瘤（PEL）以及一种淋巴增殖性疾病——多中心卡斯特曼病（MCD）的病原体。KS发展为肿瘤依赖于病毒从潜伏状态重新激活。我们和其他人已经表明，复制和转录激活因子（Rta）蛋白是病毒重新激活所必需且充分的唯一病毒基因产物。为了诱导病毒基因的重新激活和转录，Rta与经典Notch信号通路的细胞DNA结合成分Jk重组信号结合蛋白（RBP-Jk）形成复合物。这种Rta:RBP-Jk复合物的形成是病毒重新激活发生所必需的。已表明激活的Notch在KSHV感染的细胞中表达失调，并且对细胞生长和疾病进展是必需的。关于激活的Notch参与病毒重新激活的研究产生了不同的结果。在本文中，我们综述了关于KSHV导致的Notch失调及其在病毒感染和细胞发病机制中的作用的当前文献。
