Cocaine-Induced Epigenetic Changes in CD4+ T cells and HIV-1 Replication

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DESCRIPTION (provided by applicant): Drug use remains the second most common mode of exposure to HIV. Illicit drugs such as amphetamines, cocaine, marijuana, and opiates serve as cofactors for susceptibility to HIV infection and disease progression. Although clinical reports indicate an association between HIV/AIDS and use of illicit drugs, the underlying mechanism of infection susceptibility and disease progression remain unclear. One clue is that drugs such as cocaine have been shown to exert their addictive effect in part by epigenetic modifications. Although epigenetic modifications are important in HIV-1 life cycle, a role of drug abuse-associated epigenetic changes in HIV/AIDS remains unclear. My laboratory focuses on understanding the role of genome structure on HIV-1 replication. One of the goals of our research is to decipher how epigenetic modifications in transcriptosome influence HIV-1 integration. Since drugs of abuse exert their effects via epigenetic mechanisms, the SOAR support will aid our laboratory to embark on a new project addressing a role of drug abuse associated epigenetics on HIV/AIDS. Given that our laboratory is actively engaged in unraveling a role of epigenetic modifications on HIV-1 replication, the proposed SOAR application is closely related to our research program. In addition, this SOAR application will strengthen our current research program by incorporating drug abuse component. We anticipate that this pilot project will help us generate preliminary data for an R01 grant application and will bridge a major gap in the drug abuse and HIV/AIDS biology. PUBLIC HEALTH RELEVANCE: Drug use remains the second most common mode of exposure to HIV and illicit drugs serve as cofactors for susceptibility to HIV infection and disease progression. Although epigenetic modifications have been implicated in the HIV-1 life cycle, a role of drug abuse-associated epigenetic changes in HIV/AIDS remains to be established. Our proposal will unravel a link between "drug-abuse induced epigenomic changes" and "HIV-1 replication", thereby defining the contribution of epigenomic modifications to the increased risk of HIV-1 infection among drug addicts.