Premium
Cocaine enhances HIV‐1 integration in CD4 + T cells by modulating the epigenetic DNA signatures of host genome (776.3)
Author(s) -
Addai Amma,
Pandhare Jui,
Mantri Chinmay,
Dash Chandravanu
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.776.3
Subject(s) - dna methylation , epigenetics , genome , reverse transcriptase , peripheral blood mononuclear cell , biology , dna , dna replication , methylation , virology , genetics , computational biology , in vitro , gene , polymerase chain reaction , gene expression
Cocaine, a commonly abused drug among HIV patients, is known to increase HIV‐1 replication in cell cultures, peripheral blood mononuclear cells (PBMCs) and animal models. The goal of this study is to examine the effects of cocaine on HIV‐1 integration. During HIV‐1 replication, the viral genome is reverse transcribed into a dsDNA by HIV‐1 reverse transcriptase. This viral dsDNA is transported into the nucleus in the form of a pre‐integration complex (PICs) and integrates into the host genome. Our data demonstrates that cocaine treatment enhances HIV‐1 integration in primary CD4+ T cells. To understand the mechanism, we examined global DNA methylation in cocaine treated cells. Our data revealed that cocaine induced global DNA de‐methylation in CD4+ T cells. Since integration has been suggested to be disfavored in methylated DNA targets, we hypothesize that cocaine enhances integration by reducing the global DNA methylation signature of the host genome. Our in vitro studies using PICs from infected cells illustrate that integration is reduced in target DNA that are methylated compared to unmethylated target. To the best of our knowledge, this is the first report describing a role of cocaine on HIV‐1 integration in activated CD4+ T cells. We believe understanding the mechanism by which cocaine modulates HIV‐1 integration may aid in the discovery of novel targets to cure the co‐morbid condition of drug abuse and HIV/AIDS. Grant Funding Source : *Amma Addai is supported by T32 grant #2T32H007735‐17 from NIH/NHLBI to Dr. S. E. Adunyah