EV71病毒的2C蛋白通过p62挟持细胞自噬的机制和作用

Enterovirus 71 (EV71) has become an important virus that threatens the health of infants and children in our country. And it is of great significance to study the mechanism of virus replication and pathogenesis for the intervention and treatment of hand, foot and mouth disease (HFMD) caused by EV71. Enteroviruses promote virus replication by inducing autophagy have been reported. However, the mechanism of how viruses employ this process is not very clear. In previous studies, we discovered that EV71 could induce autophagy during infection, and tandem affinity purification combined with mass spectrometry showed that 2C may interact with autophagy adaptor protein-p62. We speculated that EV71 was replicated into vacuoles where the replication complex including 2C was recruited by the interaction of p62 and 2C. Therefore, after the verification of autophagy during the replication of EV71 both on cell level and mouse models and the identification of the interaction sites of 2C and p62, we will determine the role of 2C in the induction of autophagy by EV71 infection, and finally figure out the impact of the interaction of 2C and p62 on EV71 replication and pathogenicity both on cell levels and mouse models. This study will provide a theoretical basis for better understanding of the role of autophagy during viral replication, and offer data support for the establishment of replication model for enteroviruses by hijacking autophagy during infection, provide research foundation and theoretical basis for the intervention and treatment for HFMD.

肠道病毒71型（EV71）已成为危害我国婴幼儿健康的重要病原体，研究其复制和致病机理对于干预和治疗该病毒引起的手足口病具有重大意义。已有研究报道肠道病毒能通过诱导细胞自噬来促进自身复制，但其中机制还不明确。我们在前期研究中发现EV71感染过程中能引起细胞自噬，并且串联亲和纯化和质谱筛选到EV71的2C蛋白与自噬关键接头蛋白p62存在相互作用。我们推测EV71通过该相互作用将包括2C在内的病毒复制复合体转运到囊泡结构中复制。因此，我们拟在细胞和动物模型上验证EV71感染引起的自噬后，通过确定2C与p62的相互作用位点，确认2C在EV71引起的自噬中所起的作用，最后分别在细胞和动物模型上研究2C与p62的相互作用对病毒复制和致病性的影响。课题将为理解自噬在病毒感染过程中所扮演的角色提供理论依据，并为建立肠道病毒挟持自噬进行复制的模型提供数据支持，从而为干预和治疗手足口病提供研究基础和理论依据。