Dong Lanlan, Cheng Qingqing, Wang Zhihao, Yuan Peipei, Li Zhi, Sun Yan, Han Song, Yin Jun, Peng Biwen, He Xiaohua, Liu Wanhong
Pathogenic Organism and Infectious Diseases Research Institute, School of Basic Medical Sciences, Wuhan University, Donghu Road No. 185, Wuchang, Wuhan 430071, China.
Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
Viruses. 2015 Apr 2;7(4):1668-84. doi: 10.3390/v7041668.
Prototype foamy virus (PFV) is a member of the unconventional and nonpathogenic retroviruses. PFV causes lifelong chronic infections, which are partially attributable to a number of host cell factors that restrict viral replication. Herein, we identified human p53-induced RING-H2 protein (Pirh2) as a novel inhibitor of prototype foamy virus. Overexpression of Pirh2 decreased the replication of PFV, whereas knockdown of Pirh2 with specific siRNA increased PFV replication. Dual-luciferase assays and coimmunoprecipitation demonstrated that Pirh2 negatively influences the Tas-dependent transcriptional activation of the PFV long terminal repeat (LTR) and internal promoter (IP) by interacting with the transactivator Tas and down-regulating its expression. In addition, the viral inhibitory function of Pirh2 is N-terminal and RING domain dependent. Together, these results indicated that Pirh2 suppresses PFV replication by negatively impacting its transactivator Tas and the transcription of two viral promoters, which may contribute to the latency of PFV infection.
原型泡沫病毒（PFV）是非常规且无致病性的逆转录病毒成员。PFV会引发终身慢性感染，这部分归因于多种限制病毒复制的宿主细胞因子。在此，我们鉴定出人类p53诱导的RING-H2蛋白（Pirh2）是原型泡沫病毒的一种新型抑制剂。Pirh2的过表达降低了PFV的复制，而用特异性小干扰RNA（siRNA）敲低Pirh2则增加了PFV的复制。双荧光素酶测定和免疫共沉淀表明，Pirh2通过与反式激活因子Tas相互作用并下调其表达，对PFV长末端重复序列（LTR）和内部启动子（IP）的Tas依赖性转录激活产生负面影响。此外，Pirh2的病毒抑制功能依赖于N末端和RING结构域。这些结果共同表明，Pirh2通过对其反式激活因子Tas以及两个病毒启动子的转录产生负面影响来抑制PFV复制，这可能有助于PFV感染的潜伏状态。
