Aggresome-自噬是细胞清除垃圾蛋白聚集体进行自我修复的关键途径。多功能细胞蛋白14-3-3在aggreomses形成和调控自噬过程中发挥重要作用。我们前期发现PRRSV的NSP2能够通过14-3-3ε诱导aggresomes形成和激活自噬并对PRRSV感染产生影响，但具体机制尚不清楚。本项目将进一步研究14-3-3ε在NSP2诱导的自噬中的作用及自噬对PRRSV感染的影响；鉴定aggresome-自噬通路中与14-3-3ε相互作用的关键宿主蛋白并分析这些蛋白对PRRSV感染的影响，探索14-3-3ε在aggresomes招募、运输、自噬起始、自噬体形成等作用节点中功能；鉴定14-3-3ε与NSP2结合的关键区域。阐明14-3-3ε对NSP2介导的aggresome-自噬通路的调控机制。本研究为深入了解NSP2在PRRSV感染过程中作用机制和挖掘治疗PRRS新药物靶分子奠定基础。

Aggresome-autophagy pathway is essential for removal of protein aggregates to prevent their cytotoxicity. Viruses can activate aggresome-autophagy pathway to facilitate their replication. 14-3-3 is a multifuction cellular protein that is involved in regulation of aggresomes formation and autophagy. Here we found that PRRSV nonstructural protein 2 (NSP2) promoted aggresomes formation and aggresome-mediated autophagy in 293T cells. Interestingly, NSP2 can directly interacts with 14-3-3ε. However, the role of 14-3-3ε in NSP2-mediated aggresome-autophagy is unknown. Based on our preliminary data, we hypothesize that NSP2 activates aggresome-autophagy pathway under the regulation of 14-3-3ε. This proposal will determine the role of 14-3-3ε in NSP2-induced autophagy, the protein ligands of 14-3-3ε in aggresome-autophagy pathway, and the interaction domain of NSP2 and 14-3-3ε protein. We will further examine the effected of NSP2-mediated autophagy on PRRSV replication. The project will provide key findings that explain the role of NSP2 in PRRSV pathogenesis and can be exploited therapeutically.