Cocaine modulates HIV-1 integration in primary CD4+ T cells: implications in HIV-1 pathogenesis in drug-abusing patients
| Autor: | Victor Paromov, Siddharth Pratap, Chandravanu Dash, Jui Pandhare, Chinmay K. Mantri, Amma B. Addai |
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| Rok vydání: | 2015 |
| Předmět: |
CD4-Positive T-Lymphocytes
Drug Virus Integration media_common.quotation_subject Immunology Human immunodeficiency virus (HIV) HIV Infections In Vitro Techniques Biology Lymphocyte Activation medicine.disease_cause Pathogenesis Cocaine-Related Disorders Cocaine Proviruses In vivo medicine Humans Immunology and Allergy Phytohemagglutinins Cells Cultured media_common Cell Nucleus Dose-Response Relationship Drug Mechanism (biology) Virion Vesiculovirus Cell Biology Viral Load Host Defense & Pathophysiology Raltegravir Endocytosis In vitro HEK293 Cells DNA Viral Disease Progression HIV-1 Viral load medicine.drug |
| Zdroj: | Journal of Leukocyte Biology. 97:779-790 |
| ISSN: | 1938-3673 0741-5400 |
| DOI: | 10.1189/jlb.4a0714-356r |
| Popis: | 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 µM–100 µM). Proviral DNA integration in the host genome was measured by nested qPCR. Our results illustrated that cocaine from 1 µM through 50 µM 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. |
| Databáze: | OpenAIRE |
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