Cyclophilin A Associates with Enterovirus-71 Virus Capsid and Plays an Essential Role in Viral Infection as an Uncoating Regulator

作者：Jie Qing, Yaxin Wang, Yuna Sun, Jiaoyan Huang, Wenzhong Yan, Jinglan Wang, Dan Su, Ni Cheng, Jian Li, Zihe Rao, Lei Liu, Zhiyong Lou · 发表于：PLoS Pathogens · 年份：2014 · DOI：10.1371/journal.ppat.1004422 · 被引用次数：86 · 研究领域：Signaling Pathways in Disease、Viral Infections and Immunology Research、RNA regulation and disease

Viruses utilize host factors for their efficient proliferation. By evaluating the inhibitory effects of compounds in our library, we identified inhibitors of cyclophilin A (CypA), a known immunosuppressor with peptidyl-prolyl cis-trans isomerase activity, can significantly attenuate EV71 proliferation. We demonstrated that CypA played an essential role in EV71 entry and that the RNA interference-mediated reduction of endogenous CypA expression led to decreased EV71 multiplication. We further revealed that CypA directly interacted with and modified the conformation of H-I loop of the VP1 protein in EV71 capsid, and thus regulated the uncoating process of EV71 entry step in a pH-dependent manner. Our results aid in the understanding of how host factors influence EV71 life cycle and provide new potential targets for developing antiviral agents against EV71 infection.