Snapin能够调控神经细胞自噬过程，其功能紊乱可引起神经系统疾病。研究证实嗜神经性的猪血凝性脑脊髓炎病毒（PHEV）能够诱导神经细胞自噬，且其纤突蛋白(S)能与Snapin互作，推测PHEV可能通过S蛋白干扰Snapin在自噬及溶酶体降解途径中的功能，继而影响病毒的复制和传播，最终导致神经损伤。据此，本项目拟对PHEV感染或转染S蛋白过表达载体前后神经细胞的自噬、自噬降解能力和溶酶体功能等进行检测，明确PHEV/S蛋白对自噬及溶酶体降解途径的影响；RNAi/过表达Snapin或促进/抑制自噬后，接种PHEV或过表达S蛋白，研究神经细胞自噬过程和病毒复制等变化，明确细胞自噬和Snapin对PHEV复制的影响，揭示Snapin在病毒诱导细胞自噬过程中的作用机制。预期结果不仅有利于阐明PHEV的致病机制，为抗PHEV药物研究提供新的思路，而且可为冠状病毒感染与细胞自噬的关系研究提供参考依据。

Porcine hemagglutinating encephalomyelitis virus (PHEV) has a strong tropism for the nervous system. Our results showed that PHEV can induce autophagy in nerve cells, however mechanisms of PHEV-induced autophagy is not clear.Snapin-regulated late endosomal transport is critical for efficient autophagy-lysosomal function in neurons and its dysfunction can cause neurological disease.Snapin has been screened and identified which is required for binding spike glyprotein (S) of PHEV in PHEV-infected cells.In order to reveal the pathogenesis of PHEV from the cell autophagy angle,we will study on the process of autophagy and lysosomal function in PHEV-infected cells or S-transfected cells, the change of the function of snapin in the process of PHEV-induced cell autophagy and the effect of autophagy and snapin on PHEV infection and replication by RNA interference or overexpression of Snapin,and enhancement or inhibition of autophagy in PHEV-infected cells or S-transfected cells. The results provide theoretical basis for the pathogenesis of PHEV and new ideas for exploiting target drug to resist PHEV and studying on the relationship of coronavirus infection and cell autophagy.