title: Human and rhesus APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H demonstrate a conserved capacity to restrict Vif-deficient HIV-1.
abstract: Successful intracellular pathogens must evade or neutralize the innate immune defenses of their host cells and render the cellular environment permissive for replication. For example, to replicate efficiently in CD4(+) T lymphocytes, human immunodeficiency virus type 1 (HIV-1) encodes a protein called viral infectivity factor (Vif) that promotes pathogenesis by triggering the degradation of the retrovirus restriction factor APOBEC3G. Other APOBEC3 proteins have been implicated in HIV-1 restriction, but the relevant repertoire remains ambiguous. Here we present the first comprehensive analysis of the complete, seven-member human and rhesus APOBEC3 families in HIV-1 restriction. In addition to APOBEC3G, we find that three other human APOBEC3 proteins, APOBEC3D, APOBEC3F, and APOBEC3H, are all potent HIV-1 restriction factors. These four proteins are expressed in CD4(+) T lymphocytes, are packaged into and restrict Vif-deficient HIV-1 when stably expressed in T cells, mutate proviral DNA, and are counteracted by HIV-1 Vif. Furthermore, APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H of the rhesus macaque also are packaged into and restrict Vif-deficient HIV-1 when stably expressed in T cells, and they are all neutralized by the simian immunodeficiency virus Vif protein. On the other hand, neither human nor rhesus APOBEC3A, APOBEC3B, nor APOBEC3C had a significant impact on HIV-1 replication. These data strongly implicate a combination of four APOBEC3 proteins--APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H--in HIV-1 restriction.
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, Institute for Molecular Virology, Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Judd F
authors.initials: JF
authors.lastname: Hultquist
authors.forename: Joy A
authors.initials: JA
authors.lastname: Lengyel
authors.forename: Eric W
authors.initials: EW
authors.lastname: Refsland
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: LaRue
authors.forename: Lela
authors.initials: L
authors.lastname: Lackey
authors.forename: William L
authors.initials: WL
authors.lastname: Brown
authors.forename: Reuben S
authors.initials: RS
authors.lastname: Harris
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002478:Cells, Cultured; D043525:Cytosine Deaminase / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity*; D006801:Humans; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000472:pathogenicity; D037521:Virulence Factors / Q000172:deficiency*; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000172:deficiency*
chemical_list: D037521:Virulence Factors; D054320:vif Gene Products, Human Immunodeficiency Virus; C514847:vif protein, Human immunodeficiency virus 1; D043525:Cytosine Deaminase