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

PLoS Pathogens

Zihe Rao¹  Jian Li²  Wenzhong Yan³  Jiaoyan Huang³  Yuna Sun⁴  Jinglan Wang⁴  Yaxin Wang⁴  Zhiyong Lou⁴  Cheng Ni⁴  Lei Liu⁵  Dan Su⁵  Jie Qing⁶ 

[1] Beijing No. 4 High School, Beijing, China;Collaborative Innovation Center for Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China;National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing, China;School of Medicine, Tsinghua University, Beijing, China;School of Pharmacy, East China University of Science and Technology, Shanghai, China;Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, China

关键词: Virions;    Viral replication;    HIV-1;    Recombinant proteins;    RNA viruses;    Viral packaging;    Virus uncoating;    Life cycles;   

DOI  :  10.1371/journal.ppat.1004422

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY