绵羊肺腺瘤病毒（JSRV）是引起绵羊肺腺瘤病（OPA）的病原，其病毒的囊膜蛋白（ENV）具有体内外转化细胞而致瘤的罕见特征。我们前期的研究已证实JSRV-NM的ENV可引起体外NIH3T3细胞发生恶性转化，但机制不明。本项目以原有研究结果为切入点，通过研究PI3K/Akt/mTOR和MAPK信号通路在经JSRV ENV转化的体外NIH3T3细胞和绵羊绒毛膜滋养层细胞中的激活机制为靶点，结合透射电镜技术检测转化细胞中的自噬体结构和检测自噬因子Beclin1和LC3的mRNA和蛋白表达水平以及添加信号通路抑制剂调控通路激活为调节点，深入探究JSRV是如何通过调控信号通路以及自噬水平的变化来诱导其恶性转化的，然后通过体内实验在自然感染OPA病羊肺组织中和小鼠体内致瘤得到验证，从而揭示ENV致瘤的复杂机制。其研究成果对探明绵羊肺腺瘤病的发病机理以及找到防控该病的靶点具有重要的理论意义和实践意义。

Jaagsiekte sheep retrovirus (JSRV) is the causative agent of ovine pulmonary adenocarcinoma (OPA). The envelope protein(ENV) of JSRV could transform cells in vitro and also could induce tumors in vivo experiments. As previous reported, it has been identified that JSRV-NM-ENV could induce NIH3T3 cells malignant transformation in vitro, but the molecular mechanism of transformation was not clear. The previous results were used as the breakthrough point, the activated mechanism of PI3K/Akt/mTOR and MAPK pathway in JSRV-NM-ENV transformed cells in vitro was used as the research target, the autophagosome structure of cells was detected through the transmission electron microscopy technology, the levels of mRNA and protein of Beclin1 and LC3 in JSRV-NM-ENV transformed cells was also detected, in order to explore how JSRV-NM-ENV induced malignant transformation through the modulation of autophagy by PI3K/Akt/mTOR and MAPK pathway. Then the natural infected OPA lung tissues in vivo and the tumorigenesis experiment in mouse were used to verify the complex tumorigenic molecular mechanism of ENV. The research was important for the theoretical and practical significance to verify the pathogenesis of OPA and seek out the target for preventing and controlling it.