Graduate Institute of Clinical Medical Sciences, Chang-Gung University, Taoyuan, Taiwan.
Virology. 2011 May 10;413(2):194-204. doi: 10.1016/j.virol.2011.02.013. Epub 2011 Mar 4.
Lytic cycle reactivation of Kaposi's sarcoma-associated herpesvirus (KSHV) is initiated by expression of the ORF50 gene. Here we show that YY1 protein specifically binds to the ORF50 promoter (ORF50p) region in vitro and in vivo. After treatment with chemical inducers, including sodium butyrate (SB) and TPA, the levels of YY1 protein are inversely correlated with the lytic induction of KSHV in cells. Overexpression of YY1 completely blocks the ORF50p activation in transient reporter assays, while mutation at the YY1 site in the ORF50p or knockdown of YY1 protein confers an enhancement of the ORF50p activation induced by SB and TPA. YY1 overexpression in a stable cell clone HH-B2(Dox-YY1) also inhibits expression of the ORF50 and its downstream lytic genes. On the other hand, a chimeric YY1 construct that links to its coactivator E1A can disrupt viral latency. These results imply that YY1 is involved in the regulation of KSHV reactivation.
溶瘤周期再激活的卡波济氏肉瘤相关疱疹病毒（KSHV）是由 ORF50 基因的表达启动的。在这里，我们发现 YY1 蛋白在体外和体内都能特异性地结合到 ORF50 启动子（ORF50p）区域。在用化学诱导剂（包括丁酸钠（SB）和 TPA）处理后，YY1 蛋白的水平与细胞中 KSHV 的溶瘤诱导呈负相关。YY1 的过表达在瞬时报告基因检测中完全阻断了 ORF50p 的激活，而在 ORF50p 中的 YY1 位点发生突变或 YY1 蛋白的敲低则增强了 SB 和 TPA 诱导的 ORF50p 激活。在 HH-B2(Dox-YY1)稳定细胞克隆中的 YY1 过表达也抑制了 ORF50 及其下游溶瘤基因的表达。另一方面，与共激活因子 E1A 相连的嵌合 YY1 构建体可以破坏病毒潜伏。这些结果表明，YY1 参与了 KSHV 再激活的调控。
