title: Creation of chimeric human/rabbit APOBEC1 with HIV-1 restriction and DNA mutation activities.
abstract: APOBEC1 (A1) proteins from lagomorphs and rodents have deaminase-dependent restriction activity against HIV-1, whereas human A1 exerts a negligible effect. To investigate these differences in the restriction of HIV-1 by A1 proteins, a series of chimeric proteins combining rabbit and human A1s was constructed. Homology models of the A1s indicated that their activities derive from functional domains that likely act in tandem through a dimeric interface. The C-terminal region containing the leucine-rich motif and the dimerization domains of rabbit A1 is important for its anti-HIV-1 activity. The A1 chimeras with strong anti-HIV-1 activity were incorporated into virions more efficiently than those without anti-HIV-1 activity, and exhibited potent DNA-mutator activity. Therefore, the C-terminal region of rabbit A1 is involved in both its packaging into the HIV-1 virion and its deamination activity against both viral cDNA and genomic RNA. This study identifies the novel molecular mechanism underlying the target specificity of A1.
authors.affiliation: Department of Retrovirology and Self-Defense, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
authors.forename: Terumasa
authors.initials: T
authors.lastname: Ikeda
authors.affiliation: Institute for Research in Molecular Medicine, Universiti Sains Malaysia, 11800 Penang, Malaysia.
authors.forename: Eugene Boon Beng
authors.initials: EB
authors.lastname: Ong
authors.affiliation: Institute for Research in Molecular Medicine, Universiti Sains Malaysia, 11800 Penang, Malaysia.|Bio-Active Compounds Discovery Research Unit, Chemical Biology Research Group, RIKEN Center for Sustainable Resource Science, 2-1, Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Nobumoto
authors.initials: N
authors.lastname: Watanabe
authors.affiliation: World Premier International Research Center Initiative, Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita 565-0871, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Sakaguchi
authors.affiliation: World Premier International Research Center Initiative, Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita 565-0871, Japan.|Laboratory of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita 565-0871, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Maeda
authors.affiliation: Department of Retrovirology and Self-Defense, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Koito
mesh_terms: D000071479:APOBEC-1 Deaminase / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D004926:Escherichia coli / Q000235:genetics; D016680:Genome, Bacterial; D016679:Genome, Viral; D057809:HEK293 Cells; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D009153:Mutagens / Q000494:pharmacology; D009154:Mutation; D055503:Protein Multimerization; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D017386:Sequence Homology, Amino Acid; D014771:Virion / Q000187:drug effects / Q000502:physiology; D019065:Virus Assembly
chemical_list: D019380:Anti-HIV Agents; D009153:Mutagens; D011993:Recombinant Fusion Proteins; D000071479:APOBEC-1 Deaminase