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.
Copyright © 2012 Elsevier Inc. All rights reserved.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
APOBEC-3G Deaminase
-
Adult
-
Cytidine Deaminase / biosynthesis*
-
Cytidine Deaminase / immunology*
-
Cytosine Deaminase / biosynthesis
-
Cytosine Deaminase / immunology
-
Female
-
Gene Expression Profiling
-
HIV Infections / immunology
-
HIV Infections / virology
-
HIV-1 / immunology*
-
Humans
-
Leukocytes, Mononuclear / immunology
-
Leukocytes, Mononuclear / virology
-
Male
-
Middle Aged
-
Molecular Sequence Data
-
Plasma / virology
-
Proviruses / isolation & purification
-
RNA, Viral / genetics
-
RNA, Viral / isolation & purification
-
Sequence Analysis, DNA
-
Viral Load*
-
vif Gene Products, Human Immunodeficiency Virus / metabolism
Substances
-
RNA, Viral
-
vif Gene Products, Human Immunodeficiency Virus
-
APOBEC3F protein, human
-
Cytosine Deaminase
-
APOBEC-3G Deaminase
-
APOBEC3G protein, human
-
Cytidine Deaminase
Associated data
-
GENBANK/JQ409018
-
GENBANK/JQ409019
-
GENBANK/JQ409020
-
GENBANK/JQ409021
-
GENBANK/JQ409022
-
GENBANK/JQ409023
-
GENBANK/JQ409024
-
GENBANK/JQ409025
-
GENBANK/JQ409026
-
GENBANK/JQ409027
-
GENBANK/JQ409028
-
GENBANK/JQ409029
-
GENBANK/JQ409030
-
GENBANK/JQ409031
-
GENBANK/JQ409032
-
GENBANK/JQ409033
-
GENBANK/JQ409034
-
GENBANK/JQ409035
-
GENBANK/JQ409036
-
GENBANK/JQ409037
-
GENBANK/JQ409038
-
GENBANK/JQ409039
-
GENBANK/JQ409040
-
GENBANK/JQ409041