Analysis of viral gene products controlling latent and lytic replication of human herpesvirus 8

人类疱疹病毒8型（Human herpesvirus 8，HHV 8）又称卡波西肉瘤相关疱疹病毒（Kaposi's sarcoma-associated herpesvirus，KSHV），是γ-疱疹病毒科的一种病毒，被认为是卡波西肉瘤（Kapasi' s sarcoma，KS）和原发性渗出性淋巴瘤（primary effusion lymphoma，PEL）的病原体。我们研究了裂解复制的发病的分子机制。我们鉴定了裂解基因产物RTA、K5、K8、K9等，并产生了针对这些基因产物的单克隆抗体。我们还从亲本BCBL 1中分离出用KSHV感染的TPA非反应性细胞克隆。RTA通过非DNA结合机制上调K9基因，RTA通过与OCT 1相互作用上调自身启动子，而K5下调MHC I类分子，从而导致裂解复制过程中的免疫逃避。

Human herpesvirus 8 (HHV8) or Kaposi's sarcoma-associated herpesvirus (KSHV) is a member of γ-herpesviridae and supposed to be a causative agent for Kapasi' s sarcoma (KS) and primary effusion lymphoma (PEL). We investigated the molecular mechanism of the onset of lytic replication. We identified lytic gene products, RTA, K5, K8, K9 etc. and generated monoclonal antibodies against such gene products. We also isolated TPA non-reactive cell clones infected with KSHV from the parental BCBL1. Using these, we clarified that RTA was a key transcriptional regulator for the reactivation, that RTA upregulated K9 gene through non-DNA binding mechanism, that RTA upregulated its own promoter through the interaction with OCT1 and hat K5 downregulated the MHC class I, which lead to the immune evasion during lytic replication.