Tyagi Mudit, Weber Jaime, Bukrinsky Michael, Simon Gary L
Division of Infectious Diseases, Department of Medicine, The George Washington University, 2300 Eye Street, N.W., Washington, DC, 20037, USA.
Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, DC, 20037, USA.
J Neurovirol. 2016 Jun;22(3):261-74. doi: 10.1007/s13365-015-0398-z. Epub 2015 Nov 16.
Illicit drug users are a high-risk population for infection with the human immunodeficiency virus (HIV). A strong correlation exists between prohibited drug use and an increased rate of HIV transmission. Cocaine stands out as one of the most frequently abused illicit drugs, and its use is correlated with HIV infection and disease progression. The central nervous system (CNS) is a common target for both drugs of abuse and HIV, and cocaine intake further accelerates neuronal injury in HIV patients. Although the high incidence of HIV infection in illicit drug abusers is primarily due to high-risk activities such as needle sharing and unprotected sex, several studies have demonstrated that cocaine enhances the rate of HIV gene expression and replication by activating various signal transduction pathways and downstream transcription factors. In order to generate mature HIV genomic transcript, HIV gene expression has to pass through both the initiation and elongation phases of transcription, which requires discrete transcription factors. In this review, we will provide a detailed analysis of the molecular mechanisms that regulate HIV transcription and discuss how cocaine modulates those mechanisms to upregulate HIV transcription and eventually HIV replication.
非法药物使用者是感染人类免疫缺陷病毒(HIV)的高危人群。违禁药物使用与HIV传播率上升之间存在强烈关联。可卡因是最常被滥用的非法药物之一,其使用与HIV感染及疾病进展相关。中枢神经系统(CNS)是滥用药物和HIV的共同靶标,摄入可卡因会进一步加速HIV患者的神经元损伤。虽然非法药物滥用者中HIV感染率高主要归因于共用针头和无保护性行为等高风险活动,但多项研究表明,可卡因通过激活各种信号转导途径和下游转录因子来提高HIV基因表达和复制的速率。为了产生成熟的HIV基因组转录本,HIV基因表达必须经过转录的起始和延伸阶段,这需要特定的转录因子。在本综述中,我们将详细分析调节HIV转录的分子机制,并讨论可卡因如何调节这些机制以上调HIV转录并最终促进HIV复制。