Animal Health Biotechnology Group, Temasek Lifesciences Laboratory, The National University of Singapore, 1 Research Link, Singapore 117604.
Virology. 2010 Mar 1;398(1):1-11. doi: 10.1016/j.virol.2009.11.028. Epub 2009 Dec 11.
The ORF3 protein of porcine circovirus type 2 (PCV2) causes apoptosis in virus-infected cells and is not essential for virus replication. The ORF3 protein plays an important role in the pathogenesis of the PCV2 infection in mouse models and SPF piglets. The ORF3 protein interacts with the porcine homologue of Pirh2 (pPirh2), a p53-induced ubiquitin-protein E3 ligase, which regulates p53 ubiquitination. Here, we present our study analyzing the details of the molecular interaction between these three factors. Our experiments, in vitro and in vivo, show that ORF3 protein competes with p53 in binding to pPirh2. The amino acid residues 20 to 65 of the ORF3 protein are essential in this competitive interaction of ORF3 protein with pPirh2 over p53. The interaction of ORF3 protein with pPirh2 also leads to an alteration in the physiological cellular localization of pPirh2 and a significant reduction in the stability of pPirh2. These events contribute to the deregulation of p53 by pPirh2, leading to increased p53 levels and apoptosis of the infected cells.
猪圆环病毒 2 型（PCV2）的 ORF3 蛋白可导致病毒感染细胞凋亡，且其对于病毒复制并非必需。ORF3 蛋白在 PCV2 感染的小鼠模型和 SPF 仔猪中的发病机制中发挥重要作用。ORF3 蛋白与猪同源物 Pirh2（pPirh2）相互作用，后者是一种 p53 诱导的泛素蛋白 E3 连接酶，可调节 p53 的泛素化。在此，我们报告了分析这三个因素之间分子相互作用细节的研究。我们的体外和体内实验表明，ORF3 蛋白可与 pPirh2 竞争结合 p53。ORF3 蛋白与 pPirh2 的这种竞争相互作用中，ORF3 蛋白的 20 至 65 个氨基酸残基是必需的。ORF3 蛋白与 pPirh2 的相互作用还导致 pPirh2 的生理细胞定位发生改变，其稳定性显著降低。这些事件导致 pPirh2 对 p53 的调控失调，从而导致感染细胞中 p53 水平升高和凋亡。
