人肠道病毒71型(EV71)属于小核糖核酸病毒科肠道病毒属，是造成手足口病的主要病原，可引起严重的神经性疾病。EV71通过clathrin、caveolae、endophlin-A2介导的内吞途径入侵不同的细胞。我们发现clathrin途径抑制剂chlorpromazine和dynasore不抑制反而增强EV71感染A549细胞，此效应发生在病毒的内吞而非复制阶段。进一步机制研究发现敲低RhoA或Arf6显著降低EV71入侵A549细胞，提示EV71可能依赖RhoA和Arf6入侵A549细胞。由此出发本项目将继续探索相关机制，力争阐明:1)该途径的内吞机制;2)病毒内吞后在细胞内的转运方式。本项目将有助于深化EV71入侵机制的理解，并为研发新的抗病毒药物提供理论依据。

Enterovirus 71 (EV71), belonging to Piconaviridae family, Enterovirus genus, is one of the major causative agents of hand, foot and mouth disease. EV71 infection can cause severe neurological disease in some infected children. It is reported that clathrin, caveolae or endophlin-A2 mediated endocytic pathway are involved in EV71 entry into different cells. Previously we have reported chlorpromazine or dynasore, which inhibit clathrin and dynamin dependent endocytosis, enhanced EV71 infection in A549 cells. This enhancement was due to increased viral entry and not viral translation or replication. Further mechanistic study showed knockdown of RhoA and Arf6 significantly reduced EV71 infection in A549 cells, suggesting the invasion of EV71 in A549 cells may depend on RhoA and Arf6. In this study, we will further explore the mechanism of this endocytic process, including: 1) investigating the novel endocytic mechanisms; 2) revealing the viral trafficking and uncoating sites. These studies will comprehensively deepen our understanding of the invading mechanisms utilized by EV71, and help us to design new target-specific antiviral drugs.