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

描述（由申请人提供）：吸毒仍然是第二大最常见的艾滋病毒暴露方式。非法药物如安非他明、可卡因、大麻和阿片类药物是艾滋病毒感染易感性和疾病进展的辅助因素。尽管临床报告表明艾滋病毒/艾滋病与使用非法药物之间存在关联，但感染易感性和疾病进展的潜在机制仍不清楚。一条线索是，可卡因等药物的成瘾性部分是由表观遗传修饰引起的。尽管表观遗传修饰在HIV-1生命周期中很重要，但药物滥用相关的表观遗传改变在HIV/AIDS中的作用尚不清楚。我的实验室专注于了解基因组结构在HIV-1复制中的作用。我们研究的目标之一是破译转录体中的表观遗传修饰如何影响HIV-1整合。由于药物滥用通过表观遗传机制发挥作用，SOAR的支持将帮助我们的实验室开展一个新的项目，研究药物滥用与表观遗传学在艾滋病毒/艾滋病中的作用。鉴于我们的实验室正积极致力于揭示表观遗传修饰在HIV-1复制中的作用，提出的SOAR应用与我们的研究计划密切相关。此外，这个SOAR应用程序将通过纳入药物滥用成分来加强我们目前的研究计划。我们预计，这个试点项目将帮助我们为R01拨款申请提供初步数据，并将弥合药物滥用和艾滋病毒/艾滋病生物学方面的重大差距。

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.