title: APOBEC3G expression and hypermutation are inversely associated with human immunodeficiency virus type 1 (HIV-1) burden in vivo.
abstract: APOBEC3G (A3G) and APOBEC3F (A3F) reduce Vif-negative HIV-1 provirus formation and cause disabling provirus G-to-A hypermutation in vitro. However, evidence conflicts about whether they negatively impact Vif-positive HIV-1, or only enhance virus genetic diversity, in vivo. We studied peripheral blood mononuclear cells (PBMC) from 19 antiretroviral-naïve, HIV-infected adults: 12 long-term non-progressors (LTNP) and 7 non-controllers (NC). Cells from LTNP had higher A3G and A3F mRNA levels, lower provirus burden, and more A3G-hypermutated positions in provirus sequence than cells from NC. A3G mRNA level was directly associated with its Hypermutation Index (HI) and inversely associated with provirus burden. Plasma HIV-1 RNA levels were inversely associated with A3G expression levels and with HI only among subjects who had HI>1. A3G HI was not associated with provirus burden. These results indicate that A3G deaminase-dependent activity above a threshold level, and its deaminase-independent functions, contribute to decreasing Vif-positive virus replication in vivo.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Yordanka
authors.initials: Y
authors.lastname: Kourteva
authors.forename: MariaPia
authors.initials: M
authors.lastname: De Pasquale
authors.forename: Tara
authors.initials: T
authors.lastname: Allos
authors.forename: Chara
authors.initials: C
authors.lastname: McMunn
authors.forename: Richard T
authors.initials: RT
authors.lastname: D'Aquila
mesh_terms: D000071480:APOBEC-3G Deaminase; D000328:Adult; D003564:Cytidine Deaminase / Q000096:biosynthesis* / Q000276:immunology*; D043525:Cytosine Deaminase / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010949:Plasma / Q000821:virology; D011533:Proviruses / Q000302:isolation & purification; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D017422:Sequence Analysis, DNA; D019562:Viral Load; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000378:metabolism
chemical_list: D012367:RNA, Viral; D054320:vif Gene Products, Human Immunodeficiency Virus; C492906:APOBEC3F protein, human; D043525:Cytosine Deaminase; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase