title: Cellular HIV-1 inhibition by truncated old world primate APOBEC3A proteins lacking a complete deaminase domain.
abstract: The APOBEC3 (A3) deaminases are retrovirus restriction factors that were proposed as inhibitory components of HIV-1 gene therapy vectors. However, A3 mutational activity may induce undesired genomic damage and enable HIV-1 to evade drugs and immune responses. Here, we show that A3A protein from Colobus guereza (colA3A) can restrict HIV-1 replication in producer cells in a deaminase-independent manner without inducing DNA damage. Neither HIV-1 reverse transcription nor integration were significantly affected by colA3A, but capsid protein synthesis was inhibited. The determinants for colA3A restriction mapped to the N-terminal region. These properties extend to A3A from mandrills and De Brazza's monkeys. Surprisingly, truncated colA3A proteins expressing only the N-terminal 100 amino acids effectively exclude critical catalytic regions but retained potent cellular restriction activity. These highlight a unique mechanism of cellular HIV-1 restriction by several Old World monkey A3A proteins that may be exploited for functional HIV-1 cure strategies.
authors.affiliation: Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160, USA.
authors.forename: Miki
authors.initials: M
authors.lastname: Katuwal
authors.affiliation: Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160, USA.
authors.forename: Yaqiong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Schmitt
authors.affiliation: Departments of Medicine, Microbiology and Immunology University of Colorado Denver, Aurora, CO 80045, USA.
authors.forename: Kejun
authors.initials: K
authors.lastname: Guo
authors.affiliation: Departments of Medicine, Microbiology and Immunology University of Colorado Denver, Aurora, CO 80045, USA.
authors.forename: Kalani
authors.initials: K
authors.lastname: Halemano
authors.affiliation: Departments of Medicine, Microbiology and Immunology University of Colorado Denver, Aurora, CO 80045, USA.
authors.forename: Mario L
authors.initials: ML
authors.lastname: Santiago
authors.affiliation: Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160, USA. Electronic address: estephen@kumc.edu.
authors.forename: Edward B
authors.initials: EB
authors.lastname: Stephens
mesh_terms: D000818:Animals; D002460:Cell Line; D003104:Colobus; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D005622:Friend murine leukemia virus / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D009154:Mutation; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins; D014779:Virus Replication / Q000502:physiology*
chemical_list: D011994:Recombinant Proteins; D003564:Cytidine Deaminase
keywords: APOBEC3A; DNA damage; Deaminase domain; HIV-1; Restriction factor; Structure–function