TY - JOUR
T1 - APOBEC3G expression and hypermutation are inversely associated with human immunodeficiency virus type 1 (HIV-1) burden in vivo
AU - Kourteva, Yordanka
AU - De Pasquale, MariaPia
AU - Allos, Tara
AU - McMunn, Chara
AU - D'Aquila, Richard T.
N1 - Funding Information:
We thank Lorraine Sutton for help with sequencing, Gustavo Kijak for providing the Hyperpack software and Ambra Pozzi for critically reading the manuscript. This work was supported by Vanderbilt-Meharry Center for AIDS Research (CFAR) Developmental Core Awards (to YK and MPD) and has been facilitated by the infrastructure and resources provided by the Vanderbilt-Meharry CFAR, an NIH funded program # P30 AI 54999 . Funding from an investigator-initiated grant from Merck to RD is also appreciated. We are thankful to the AIDS Research and Reference Reagents Program, Division of AIDS, NIAID, NIH for providing ACH-2 cells.
PY - 2012/8/15
Y1 - 2012/8/15
N2 - 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.
AB - 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.
KW - APOBEC3F
KW - APOBEC3G
KW - Cytidine deaminase
KW - G-to-A hypermutations
KW - HIV-1
KW - Long-term non-progressors
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U2 - 10.1016/j.virol.2012.03.018
DO - 10.1016/j.virol.2012.03.018
M3 - Article
C2 - 22579353
AN - SCOPUS:84861797295
SN - 0042-6822
VL - 430
SP - 1
EP - 9
JO - Virology
JF - Virology
IS - 1
ER -
