猪内源性反转录病毒（PERV）是猪-人异种移植、猪源制品与生物活性材料中最受关注的病原体。我们在前期研究中证实天然免疫抗病毒分子APOBEC3F（pA3F）可有效抑制PERV复制，但PERV在自然宿主体内逃逸pA3F作用的机制尚不清楚。结合文献及前期结果，我们推测PERV可能通过某种效应蛋白或某种机制促成了pA3F在发挥作用前被降解，由此逃逸了pA3F的抗病毒作用。本项目中，首先筛选与pA3F互作的病毒效应蛋白及宿主细胞关键蛋白，再逐步验证病毒效应蛋白与宿主细胞关键蛋白是否参与并促成了pA3F降解，鉴定病毒效应蛋白-pA3F-宿主细胞关键蛋白之间发生互作的方式及通路，阐明PERV在pA3F作用下的免疫逃逸机制。本项目的实施与完成，有助于深入评价异种移植的病毒安全性，揭示反转录病毒在APOBEC3作用下不依赖Vif的新型免疫逃逸机制，对于寻找抗反转录病毒新的药物作用靶标有重要意义。

Porcine endogenous retrovirus (PERV) is the most concerned pathogen in xenotransplantation and porcine biopharmaceuticals. In our previous studies, we demonstrated that innate antiviral molecule APOBEC3F (pA3F) could inhibit the reproduction of PERV efficiently. However, it’s not clear how PERVs escape from the repression of pA3F in its natural host. According to the literatures and our previous results, we hypothesize that certain virus proteins and/or host cell proteins cause the degradation of pA3F via some mechanism. In this program, we will do further studies to explore the mechanism of PERV escaping from APOBEC3F. Firstly, proteins interacting with pA3F will be screened and verified. Then we will identify if these proteins cause the degradation of pA3F and how these proteins interact with each other. Implementation of this project is significant to do further appraisal of the viral safety of xenotransplantation. The results of this project will reveal a novel immune scape mechanism independent of the expression of Vif, which will facilitate the identification of new anti-retroviral drug targets.