title: GANP interacts with APOBEC3G and facilitates its encapsidation into the virions to reduce HIV-1 infectivity.
abstract: The ssDNA-dependent deoxycytidine deaminase apolipoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like 3G (A3G) is a potent restrictive factor against HIV-1 virus lacking viral-encoded infectivity factor (Vif) in CD4(+) T cells. A3G antiretroviral activity requires its encapsulation into HIV-1 virions. In this study, we show that germinal center-associated nuclear protein (GANP) is induced in activated CD4(+) T cells and physically interacts with A3G. Overexpression of GANP augments the A3G encapsidation into the virion-like particles and ΔVif HIV-1 virions. GANP is encapsidated in HIV-1 virion and modulates A3G packaging into the cores together with cellular RNAs, including 7SL RNA, and with unspliced HIV-1 genomic RNA. GANP upregulation leads to a significant increase in A3G-catalyzed G→A hypermutation in the viral genome and suppression of HIV-1 infectivity in a single-round viral infection assay. Conversely, GANP knockdown caused a marked increase in HIV-1 infectivity in a multiple-round infection assay. The data suggest that GANP is a cellular factor that facilitates A3G encapsidation into HIV-1 virions to inhibit viral infectivity.
authors.affiliation: Department of Immunology, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Maeda
authors.affiliation: Department of Immunology, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan.
authors.forename: Sarah Ameen
authors.initials: SA
authors.lastname: Almofty
authors.affiliation: Department of Immunology, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan.
authors.forename: Shailendra Kumar
authors.initials: SK
authors.lastname: Singh
authors.affiliation: Department of Immunology, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan.
authors.forename: Mohammed Mansour Abbas
authors.initials: MMA
authors.lastname: Eid
authors.affiliation: Department of Immunology, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan.
authors.forename: Mayuko
authors.initials: M
authors.lastname: Shimoda
authors.affiliation: Department of Retrovirology and Self-Defense, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan.
authors.forename: Terumasa
authors.initials: T
authors.lastname: Ikeda
authors.affiliation: Department of Retrovirology and Self-Defense, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Koito
authors.affiliation: Departments of Biological Sciences and Chemistry, University of Southern California, Los Angeles, CA 90089-2910.
authors.forename: Phuong
authors.initials: P
authors.lastname: Pham
authors.affiliation: Departments of Biological Sciences and Chemistry, University of Southern California, Los Angeles, CA 90089-2910.
authors.forename: Myron F
authors.initials: MF
authors.lastname: Goodman
authors.affiliation: Department of Immunology, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Sakaguchi
mesh_terms: D000071480:APOBEC-3G Deaminase; D000123:Acetyltransferases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003564:Cytidine Deaminase / Q000737:chemistry / Q000502:physiology*; D016341:Genes, vif; D015497:HIV-1 / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation; D009154:Mutation; D025941:Protein Interaction Mapping; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020733:RNA, Small Cytoplasmic / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D018271:Signal Recognition Particle / Q000378:metabolism; D015854:Up-Regulation; D014771:Virion / Q000378:metabolism* / Q000648:ultrastructure; D014774:Virulence; D014779:Virus Replication; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000172:deficiency; D058727:RNA, Small Untranslated
chemical_list: C115990:7SL RNA; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D020733:RNA, Small Cytoplasmic; D034741:RNA, Small Interfering; D012367:RNA, Viral; D018271:Signal Recognition Particle; D054320:vif Gene Products, Human Immunodeficiency Virus; C514847:vif protein, Human immunodeficiency virus 1; D000123:Acetyltransferases; C406825:MCM3AP protein, human; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase; D058727:RNA, Small Untranslated