4.4 Article

APOBEC3G expression and hypermutation are inversely associated with human immunodeficiency virus type 1 (HIV-1) burden in vivo

Journal

VIROLOGY
Volume 430, Issue 1, Pages 1-9

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2012.03.018

Keywords

HIV-1; APOBEC3G; APOBEC3F; G-to-A hypermutations; Long-term non-progressors; Cytidine deaminase

Categories

Funding

  1. Vanderbilt-Meharry Center for AIDS Research (CFAR) Developmental Core Awards
  2. NIH [P30 AI 54999]
  3. Merck

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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-naive, 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. (c) 2012 Elsevier Inc. All rights reserved.

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