title: Cyclophilin A associates with enterovirus-71 virus capsid and plays an essential role in viral infection as an uncoating regulator.
abstract: 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.
authors.affiliation: Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, China; School of Medicine, Tsinghua University, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Qing
authors.affiliation: School of Medicine, Tsinghua University, Beijing, China; National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing, China.
authors.forename: Yaxin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing, China.
authors.forename: Yuna
authors.initials: Y
authors.lastname: Sun
authors.affiliation: School of Medicine, Tsinghua University, Beijing, China.
authors.forename: Jiaoyan
authors.initials: J
authors.lastname: Huang
authors.affiliation: School of Pharmacy, East China University of Science and Technology, Shanghai, China.
authors.forename: Wenzhong
authors.initials: W
authors.lastname: Yan
authors.affiliation: School of Medicine, Tsinghua University, Beijing, China.
authors.forename: Jinglan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Collaborative Innovation Center for Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Su
authors.affiliation: Beijing No. 4 High School, Beijing, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Ni
authors.affiliation: School of Pharmacy, East China University of Science and Technology, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Medicine, Tsinghua University, Beijing, China; National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing, China.
authors.forename: Zihe
authors.initials: Z
authors.lastname: Rao
authors.affiliation: Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: School of Medicine, Tsinghua University, 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.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Lou
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology; D002213:Capsid / Q000378:metabolism*; D036022:Capsid Proteins / Q000378:metabolism*; D021984:Cyclophilin A / Q000378:metabolism*; D029821:Enterovirus A, Human / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D036022:Capsid Proteins; D021984:Cyclophilin A