title: The tumour suppressor APC promotes HIV-1 assembly via interaction with Gag precursor protein.
abstract: Diverse cellular proteins and RNAs are tightly regulated in their subcellular localization to exert their local function. Here we report that the tumour suppressor adenomatous polyposis coli protein (APC) directs the localization and assembly of human immunodeficiency virus (HIV)-1 Gag polyprotein at distinct membrane components to enable the efficient production and spread of infectious viral particles. A proteomic analysis and subsequent biomolecular interaction assay reveals that the carboxyl terminus of APC interacts with the matrix region of Gag. Ectopic expression of APC, but not its familial adenomatous polyposis-related truncation mutant, prominently enhances HIV-1 production. Conversely, the depletion of APC leads to a significant decrease in membrane targeting of viral components, resulting in the severe loss of production of infectious virions. Furthermore, APC promotes the directional assembly of viral components at virological synapses, thereby facilitating cell-to-cell viral transmission. These findings reveal an unexpected role of APC in the directional spread of HIV-1.
authors.affiliation: Department of Microbiology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Miyakawa
authors.affiliation: Department of Microbiology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan.
authors.forename: Mayuko
authors.initials: M
authors.lastname: Nishi
authors.affiliation: Department of Microbiology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Matsunaga
authors.affiliation: Advanced Medical Research Center, Yokohama City University, Yokohama 236-0004, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Okayama
authors.affiliation: Department of Microbiology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Anraku
authors.affiliation: Department of Microbiology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Kudoh
authors.affiliation: Advanced Medical Research Center, Yokohama City University, Yokohama 236-0004, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Hirano
authors.affiliation: Infectious Disease Surveillance Center, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kimura
authors.affiliation: Kitasato Institute for Life Sciences and Graduate School for Infection Control, Kitasato University, Tokyo 108-8641, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Morikawa
authors.affiliation: Department of Microbiology, National University of Singapore, Singapore 117597, Singapore.
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: Akira
authors.initials: A
authors.lastname: Ono
authors.affiliation: Department of Microbiology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan.
authors.forename: Akihide
authors.initials: A
authors.lastname: Ryo
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000821:virology*; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D009154:Mutation; D011485:Protein Binding; D040901:Proteomics; D034741:RNA, Small Interfering / Q000378:metabolism; D019065:Virus Assembly / Q000502:physiology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; D034741:RNA, Small Interfering; D054301:gag Gene Products, Human Immunodeficiency Virus