title: The Golgi protein ACBD3 facilitates Enterovirus 71 replication by interacting with 3A.
abstract: Enterovirus 71 (EV71) is a human pathogen that causes hand, foot, mouth disease and neurological complications. Although EV71, as well as other enteroviruses, initiates a remodeling of intracellular membrane for genomic replication, the regulatory mechanism remains elusive. By screening human cDNA library, we uncover that the Golgi resident protein acyl-coenzyme A binding domain-containing 3 (ACBD3) serves as a target of the 3A protein of EV71. This interaction occurs in cells expressing 3A or infected with EV71. Genetic inhibition or deletion of ACBD3 drastically impairs viral RNA replication and plaque formation. Such defects are corrected upon restoration of ACBD3. In infected cells, EV71 3A redirects ACBD3, to the replication sites. I44A or H54Y substitution in 3A interrupts the binding to ACBD3. As such, viral replication is impeded. These results reveal a mechanism of EV71 replication that involves host ACBD3 for viral replication.
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing P.R. China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Lei
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing P.R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: Xiao
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing P.R. China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, University of Illinois, Chicago, United States of America.
authors.forename: Yijie
authors.initials: Y
authors.lastname: Ma
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing P.R. China.
authors.forename: Jianli
authors.initials: J
authors.lastname: Qi
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wu
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing P.R. China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, University of Illinois, Chicago, United States of America.
authors.forename: Bin
authors.initials: B
authors.lastname: He
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing P.R. China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hanzhou 310003, Zhejiang Province, China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Wang
mesh_terms: D020823:ADP-Ribosylation Factor 1 / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism; D029821:Enterovirus A, Human / Q000235:genetics / Q000502:physiology*; D016679:Genome, Viral; D006056:Golgi Apparatus / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism*; D014779:Virus Replication
chemical_list: C449459:ACBD3 protein, human; D048868:Adaptor Proteins, Signal Transducing; D000596:Amino Acids; C120445:GBF1 protein, human; D020662:Guanine Nucleotide Exchange Factors; D008565:Membrane Proteins; D014764:Viral Proteins; D020823:ADP-Ribosylation Factor 1