title: APOBEC3G complexes decrease human immunodeficiency virus type 1 production.
abstract: APOBEC3G (A3G) is packaged into human immunodeficiency virus type 1 (HIV-1) virions unless HIV-1 virion infectivity factor (Vif) counteracts it. Virion A3G restricts HIV-1 reverse transcription and integration in target cells. Some A3G in producer cells colocalizes with specific cytoplasmic structures, in what are called "A3G complexes" here. Functional effects of producer cell A3G complexes on HIV-1 replication were studied. HeLa cells were cotransfected with HIV-1 constructs producing pseudoviruses, as well as either wild-type (WT) A3G or a mutant A3G (C97A, Y124A, W127A, or D128K A3G). Pseudovirus particle production was decreased from cells expressing any of the A3Gs that formed complexes by 24 h after transfection, relative to cells with C97A A3G that did not form detectable A3G complexes by 24 h or A3G-negative cells. The intracellular HIV-1 Gag half-life was shorter in cells containing A3G complexes than in those lacking complexes. HIV-1 virion output was decreased in a single round of replication from a T cell line containing A3G complexes (CEM cells) after infection with Vif-negative HIV-1, compared to Vif-positive HIV-1 that depleted A3G. Levels of production of Vif-negative and Vif-positive virus were similar from cells not containing A3G (CEM-SS cells). Knockdown of the mRNA processing body (P-body) component RCK/p54, eliminated A3G complex formation, and increased HIV-1 production. We conclude that endogenous A3G complexes in producer cells decrease HIV-1 production if not degraded by Vif.
authors.affiliation: Division of Infectious Disease, Department of Medicine, Vanderbilt University School of Medicine, AA-2205E Medical Center North, Nashville, TN 37232-2358, USA.
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Martin
authors.forename: Megan
authors.initials: M
authors.lastname: Johnson
authors.forename: Richard T
authors.initials: RT
authors.lastname: D'Aquila
mesh_terms: D000071480:APOBEC-3G Deaminase; D002460:Cell Line; D003564:Cytidine Deaminase / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D004847:Epithelial Cells / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology*; D006801:Humans; D050505:Mutant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D014779:Virus Replication; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000378:metabolism; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: D050505:Mutant Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; D054320:vif Gene Products, Human Immunodeficiency Virus; C514847:vif protein, Human immunodeficiency virus 1; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase