title: Inhibition of HIV-1 assembly by coiled-coil domain containing protein 8 in human cells.
abstract: Human Immunodeficiency Virus type 1 (HIV-1) major structure protein Gag is synthesized in the cytoplasm, assembles on the plasma membrane, subsequently buds and releases. HIV-1 viral particles incorporate a number of host proteins to facilitate or inhibit HIV-1 replication. Here we identify a new host protein, coiled-coil domain containing protein 8 (CCDC8), in HIV-1 particles. Incorporation of CCDC8 into virions is dependent on the interaction between CCDC8 and Gag matrix region. Exogenous overexpression of CCDC8 can strongly inhibit HIV-1 production, up to ~30 fold. CCDC8 is a membrane-associated protein. The interaction between exogenously expressed CCDC8 and Gag on the plasma membrane changes the assembly of Gag, and redirects it into intracellular sites, or causes Gag endocytosis. CCDC8, along with cytoskeleton protein obscuring-like1 (Obsl1) and E3 ligase Cul7, induces Gag polyubiquitination and degradation. Thus we identify a new host protein and a new pathway for HIV-1 Gag polyubiquitination and degradation. This pathway presents potential therapeutic strategies against HIV infection.
authors.affiliation: School of Medicine, Nankai University, Tianjin, China, 300071.|Lady Davis Institute, Jewish General Hospital, McGill University, Canada, H3T 1E2.|State Key Laboratory for Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wei
authors.affiliation: Lady Davis Institute, Jewish General Hospital, McGill University, Canada, H3T 1E2.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Mi
authors.initials: M
authors.lastname: Liu
authors.affiliation: Lady Davis Institute, Jewish General Hospital, McGill University, Canada, H3T 1E2.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Lady Davis Institute, Jewish General Hospital, McGill University, Canada, H3T 1E2.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Lady Davis Institute, Jewish General Hospital, McGill University, Canada, H3T 1E2.
authors.forename: Meijuan
authors.initials: M
authors.lastname: Niu
authors.affiliation: School of Medicine, Nankai University, Tianjin, China, 300071.|State Key Laboratory for Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.|Peking University Health Science Center, Beijing, China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Lady Davis Institute, Jewish General Hospital, McGill University, Canada, H3T 1E2.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Kleiman
mesh_terms: D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm; D004705:Endocytosis; D015870:Gene Expression; D015658:HIV Infections / Q000378:metabolism* / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D059748:Proteolysis; D054875:Ubiquitination; D019065:Virus Assembly; D014779:Virus Replication; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000378:metabolism
chemical_list: C569196:CCDC8 protein, human; D002352:Carrier Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus