title: HIV-1 Vif adaptation to human APOBEC3H haplotypes.
abstract: Several human APOBEC3 deaminases can inhibit HIV-1 replication in vitro. HIV-1 Vif counteracts this restriction by targeting APOBEC3 for proteasomal degradation. Human APOBEC3H (A3H) is highly polymorphic, with natural variants differing considerably in anti-HIV-1 activity in vitro. To examine HIV-1 adaptation to variation in A3H activity in a natural infection context, we determined the A3H haplotypes and Vif sequences from 76 recently infected HIV-1 patients. We detected A3H-specific Vif changes suggesting viral adaptation. The patient-derived Vif sequences were used to engineer viruses that specifically differed in their ability to counteract A3H. Replication of these Vif-variant viruses in primary T cells naturally expressing active or inactive A3H haplotypes showed that endogenously expressed A3H restricts HIV-1 replication. Proviral DNA from A3H-restricted viruses showed high levels of G-to-A mutations in an A3H-specific GA dinucleotide context. Taken together, our data validate A3H expressed at endogenous levels as a bona fide HIV-1 restriction factor.
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Marcel
authors.initials: M
authors.lastname: Ooms
authors.forename: Bonnie
authors.initials: B
authors.lastname: Brayton
authors.forename: Michael
authors.initials: M
authors.lastname: Letko
authors.forename: Susan M
authors.initials: SM
authors.lastname: Maio
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Pilcher
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Hecht
authors.forename: Jason D
authors.initials: JD
authors.lastname: Barbour
authors.forename: Viviana
authors.initials: V
authors.lastname: Simon
mesh_terms: D000220:Adaptation, Biological; D000619:Aminohydrolases / Q000037:antagonists & inhibitors* / Q000276:immunology; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification / Q000502:physiology*; D006239:Haplotypes; D054884:Host-Pathogen Interactions; D006801:Humans; D011533:Proviruses / Q000235:genetics; D059386:Reverse Genetics; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D013601:T-Lymphocytes / Q000821:virology; D014779:Virus Replication; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000235:genetics* / Q000378:metabolism*
chemical_list: D004279:DNA, Viral; D054320:vif Gene Products, Human Immunodeficiency Virus; C514847:vif protein, Human immunodeficiency virus 1; C529313:APOBEC3H protein, human; D000619:Aminohydrolases