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.