functional analysis of human herpesvirus encoded kinases

卡波西肉瘤相关疱疹病毒（KSHV），也称为人类疱疹病毒8，与卡波西肉瘤（KS）和艾滋病相关的原发性渗出性淋巴瘤（PEL）有关。本文对KSHV编码蛋白ORF21、ORF36和ORF73的功能和细胞内代谢进行了研究。ORF21和ORF36分别作为核苷和蛋白激酶发挥功能。有趣的是，ORF36可以磷酸化Rb，导致E2F活化并进入S期。KSHV的潜伏相关核抗原（拉娜）ORF 73是KSHV DNA维持所必需的，并被认为在KSHV的潜伏和肿瘤发生中起重要作用。我们研究了拉娜的代谢和翻译后加工。我们发现相对少量的全长拉娜蛋白在C端区域被切割，产生拉娜的C端片段，引起抗凋亡。此外，我们还发现了几种抑制KSHV DNA复制的抗KSHV药物。

Kaposi's sarcoma associated herpesvirus(KSHV), also known as human herpesvirus 8, is associated with Kaposi's sarcoma(KS) and AIDS-related primary effusion lymphoma(PEL). Here we have elucidated functions and intracellular metabolisms of KSHV encoded proteins, such as ORF21, ORF36 and ORF73. ORF21 and ORF36 functions as nucleoside and protein kinase, respectively. Interestingly, ORF36 can phosphorylate Rb, resulting in activation of E2F and progression to S phase. It have been known that ORF73, latency-associated nuclear antigen(LANA) of KSHV is required for maintenance of KSHV DNA and is believed to play an important role in KSHV latency and tumorigenesis. We have studied the metabolisms and post-translational processing of LANA. We found that a relatively small number of full-length LANA proteins are cleaved at C-terminal region and produced C-terminal fragments of LANA, causing anti-apoptosis. Furthermore, we found several anti KSHV agents, which suppress the KSHV DNA replication.