title: Human genome-wide RNAi screen reveals host factors required for enterovirus 71 replication.
abstract: Enterovirus 71 (EV71) is a neurotropic enterovirus without antivirals or vaccine, and its host-pathogen interactions remain poorly understood. Here we use a human genome-wide RNAi screen to identify 256 host factors involved in EV71 replication in human rhabdomyosarcoma cells. Enrichment analyses reveal overrepresentation in processes like mitotic cell cycle and transcriptional regulation. We have carried out orthogonal experiments to characterize the roles of selected factors involved in cell cycle regulation and endoplasmatic reticulum-associated degradation. We demonstrate nuclear egress of CDK6 in EV71 infected cells, and identify CDK6 and AURKB as resistance factors. NGLY1, which co-localizes with EV71 replication complexes at the endoplasmatic reticulum, supports EV71 replication. We confirm importance of these factors for EV71 replication in a human neuronal cell line and for coxsackievirus A16 infection. A small molecule inhibitor of NGLY1 reduces EV71 replication. This study provides a comprehensive map of EV71 host factors and reveals potential antiviral targets.
authors.affiliation: Department of Microbiology and Immunology, National University of Singapore, Singapore 117597, Singapore.
authors.forename: Kan Xing
authors.initials: KX
authors.lastname: Wu
authors.affiliation: Department of Microbiology and Immunology, National University of Singapore, Singapore 117597, Singapore.
authors.forename: Patchara
authors.initials: P
authors.lastname: Phuektes
authors.affiliation: Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138673, Singapore.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138673, Singapore.
authors.forename: Germaine Yen Lin
authors.initials: GY
authors.lastname: Goh
authors.affiliation: Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138673, Singapore.
authors.forename: Dimitri
authors.identifier: 0000-0002-9282-3324
authors.initials: D
authors.lastname: Moreau
authors.affiliation: Department of Microbiology and Immunology, National University of Singapore, Singapore 117597, Singapore.
authors.forename: Vincent Tak Kwong
authors.initials: VT
authors.lastname: Chow
authors.affiliation: Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138673, Singapore.
authors.forename: Frederic
authors.initials: F
authors.lastname: Bard
authors.affiliation: Department of Microbiology and Immunology, National University of Singapore, Singapore 117597, Singapore.|Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138673, Singapore.
authors.forename: Justin Jang Hann
authors.initials: JJ
authors.lastname: Chu
mesh_terms: D045744:Cell Line, Tumor; D060467:Disease Resistance / Q000235:genetics; D029821:Enterovirus A, Human / Q000254:growth & development* / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human / Q000235:genetics*; D054884:Host-Pathogen Interactions; D006801:Humans; D034622:RNA Interference; D012208:Rhabdomyosarcoma / Q000235:genetics / Q000473:pathology / Q000821:virology; D014779:Virus Replication