机构:[1]Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, China[2]School of Medicine, Tsinghua University, Beijing, China[3]National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing, China[4]School of Pharmacy, East China University of Science and Technology, Shanghai, China[5]Collaborative Innovation Center for Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China四川大学华西医院[6]Beijing No. 4 High School, Beijing, China
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.
基金:
This work was supported by the Ministry of Science and Technology 973 (grant no. 2013CB911103 and 2014CB542800), the National Natural Science
Foundation of China (grant nos. 81322023, 91313301, 31170678, 31370733 and 31000332), and The Importation and Development of High-Caliber Talents Project
of Beijing Municipal Institutions (grant no. YETP0166)
语种:
外文
PubmedID:
中科院(CAS)分区:
出版当年[2014]版:
大类|1 区医学
小类|1 区寄生虫学1 区病毒学2 区微生物学
最新[2023]版:
大类|1 区医学
小类|1 区微生物学1 区寄生虫学1 区病毒学
第一作者:
第一作者机构:[1]Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, China[2]School of Medicine, Tsinghua University, Beijing, China
共同第一作者:
通讯作者:
通讯机构:[2]School of Medicine, Tsinghua University, Beijing, China[5]Collaborative Innovation Center for Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China
推荐引用方式(GB/T 7714):
Jie Qing,Yaxin Wang,Yuna Sun,et al.Cyclophilin A associates with enterovirus-71 virus capsid and plays an essential role in viral infection as an uncoating regulator.[J].PLoS pathogens.2014,10(10):e1004422.doi:10.1371/journal.ppat.1004422.
APA:
Jie Qing,Yaxin Wang,Yuna Sun,Jiaoyan Huang,Wenzhong Yan...&Zhiyong Lou.(2014).Cyclophilin A associates with enterovirus-71 virus capsid and plays an essential role in viral infection as an uncoating regulator..PLoS pathogens,10,(10)
MLA:
Jie Qing,et al."Cyclophilin A associates with enterovirus-71 virus capsid and plays an essential role in viral infection as an uncoating regulator.".PLoS pathogens 10..10(2014):e1004422