Cocaine modulates HIV‐1 integration in primary CD4+ T cells: implications in HIV‐1 pathogenesis in drug‐abusing patients. Issue 4 (17th February 2015)

• Record Type: Journal Article
• Authors: Addai, Amma B.; Pandhare, Jui; Paromov, Victor; Mantri, Chinmay K.; Pratap, Siddharth; Dash, Chandravanu
• Is Part Of: Journal of leukocyte biology. Volume 97:Issue 4(2015)
• Page Start: 779
• Page End: 790
• Publication Date: 2015-02-17
• Subjects: preintegration complex -- Raltegravir -- mass spectrometry; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.4A0714-356R
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract : Cocaine's effect on HIV‐1 integration is facilitated by its ability to enhance preintegration complex mediated integration activity. Abstract : Epidemiologic studies suggest that cocaine abuse worsens HIV‐1 disease progression. Increased viral load has been suggested to play a key role for the accelerated HIV disease among cocaine‐abusing patients. The goal of this study was to investigate whether cocaine enhances proviral DNA integration as a mechanism to increase viral load. We infected CD4 + T cells that are the primary targets of HIV‐1 in vivo and treated the cells with physiologically relevant concentrations of cocaine (1 µ M–100 µ M). Proviral DNA integration in the host genome was measured by nested qPCR. Our results illustrated that cocaine from 1 µ M through 50 µ M increased HIV‐1 integration in CD4 + T cells in a dose‐dependent manner. As integration can be modulated by several early postentry steps of HIV‐1 infection, we examined the direct effects of cocaine on viral integration by in vitro integration assays by use of HIV‐1 PICs. Our data illustrated that cocaine directly increases viral DNA integration. Furthermore, our MS analysis showed that cocaine is able to enter CD4 + T cells and localize to the nucleus‐. In summary, our data provide strong evidence that cocaine can increase HIV‐1 integration in CD4 + T cells. Therefore, we hypothesize that increased HIV‐1 integration is a novel mechanism by which cocaine enhances viral load and worsens disease progression in drug‐abusing HIV‐1 patients.