title: Human enterovirus 71 protein interaction network prompts antiviral drug repositioning.
abstract: As a predominant cause of human hand, foot, and mouth disease, enterovirus 71 (EV71) infection may lead to serious diseases and result in severe consequences that threaten public health and cause widespread panic. Although the systematic identification of physical interactions between viral proteins and host proteins provides initial information for the recognition of the cellular mechanism involved in viral infection and the development of new therapies, EV71-host protein interactions have not been explored. Here, we identified interactions between EV71 proteins and host cellular proteins and confirmed the functional relationships of EV71-interacting proteins (EIPs) with virus proliferation and infection by integrating a human protein interaction network and by functional annotation. We found that most EIPs had known interactions with other viruses. We also predicted ATP6V0C as a broad-spectrum essential host factor and validated its essentiality for EV71 infection in vitro. EIPs and their interacting proteins were more likely to be targets of anti-inflammatory and neurological drugs, indicating their potential to serve as host-oriented antiviral targets. Thus, we used a connectivity map to find drugs that inhibited EIP expression. We predicted tanespimycin as a candidate and demonstrated its antiviral efficiency in vitro. These findings provide the first systematic identification of EV71-host protein interactions, an analysis of EIP protein characteristics and a demonstration of their value in developing host-oriented antiviral therapies.
authors.affiliation: Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850, China.|Department of Traditional Chinese Medicine and Neuroimmunopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Li
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Radiation Medicine, Beijing 102206, China.
authors.forename: Chaozhi
authors.initials: C
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Radiation Medicine, Beijing 102206, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Qingjun
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Qiling
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Qiyue
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Bo
authors.affiliation: Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Shengqi
authors.initials: S
authors.lastname: Wang
mesh_terms: D000998:Antiviral Agents / Q000302:isolation & purification* / Q000494:pharmacology*; D029821:Enterovirus A, Human / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D060066:Protein Interaction Maps; D014764:Viral Proteins / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D014764:Viral Proteins