title: A chimeric human APOBEC3A protein with a three amino acid insertion confers differential HIV-1 and adeno-associated virus restriction.
abstract: Old World monkey (OWM) and hominid APOBEC3Aproteins exhibit differential restriction activities against lentiviruses and DNA viruses. Human APOBEC3A(hA3A)has weak restriction activity against HIV-1Δvifbut is efficiently restricted by an artificially generated chimeric from mandrills (mndA3A/G). We show that a chimeric hA3Acontaining the "WVS" insertion (hA3A[(27)WVS(29)]) conferred potent HIV-1restriction activity. Analysis of each amino acid of the "WVS" motif show that the length and not necessarily the charge or hydrophobicity of the amino acids accounted for restriction activity. Our results suggest that hA3A[(27)WVS(29)]restricts HIV-1at the level of reverse transcription in target cells. Finally, our results suggest that insertion of "WVS" into hA3Amodestly reduces restriction of adeno-associated virus 2(AAV-2)while insertion of the AC Loop1region of the mndA3A/G into hA3A abolished AAV-2 restriction, strengthening the role of this molecular interface in the functional evolution of primate A3A.
authors: Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, 2000 Hixon Hall, 3901 Rainbow Blvd., Kansas City, KS 66160, United States.
authors: Yaqiong
authors: Y
authors: Wang
authors: Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, 2000 Hixon Hall, 3901 Rainbow Blvd., Kansas City, KS 66160, United States.
authors: Zekun
authors: Z
authors: Wang
authors: Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, 2000 Hixon Hall, 3901 Rainbow Blvd., Kansas City, KS 66160, United States.
authors: Ankita
authors: A
authors: Pramanik
authors: Departments of Medicine, Microbiology and Immunology, University of Colorado, Denver Aurora, CO 80045, United States.
authors: Mario L
authors: ML
authors: Santiago
authors: Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, 2000 Hixon Hall, 3901 Rainbow Blvd., Kansas City, KS 66160, United States.
authors: Jianming
authors: J
authors: Qiu
authors: Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, 2000 Hixon Hall, 3901 Rainbow Blvd., Kansas City, KS 66160, United States. Electronic address: estephen@kumc.edu.
authors: Edward B
authors: EB
authors: Stephens
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000235:genetics*; D000818:Animals; D003564:Cytidine Deaminase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D000229:Dependovirus; D060467:Disease Resistance; D015658:HIV Infections / Q000378:metabolism* / Q000821:virology*; D015497:HIV-1; D054884:Host-Pathogen Interactions; D006801:Humans; D016254:Mutagenesis, Insertional; D010322:Parvoviridae Infections / Q000378:metabolism* / Q000821:virology*; D021381:Protein Transport; D011506:Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication
chemical_list: D000596:Amino Acids; D011506:Proteins; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; C121399:APOBEC3A protein, human; D003564:Cytidine Deaminase
keywords: AAV-2; AC-Loop 1; APOBEC3A; HIV-1; Parvovirus; Protein structure; Site directed mutagenesis; Virus restriction