Mechanisms of Cocaine-Induced HIV-1 infection in NHA

NHA 中可卡因诱导 HIV-1 感染的机制

• 批准号: 7120907
• 负责人: JESSICA L REYNOLDS
• 金额: $ 4.88万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-04 至 2008-04-03
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7120907
• 关键词: cocaine; infection; mitogen activated protein kinase

DESCRIPTION (provided by applicant): In 2003, an estimated 2.3 million Americans were active cocaine users. The US is currently experiencing an epidemic of cocaine use entangled with HIV-1 infection. The central nervous system (CNS) is a common target for both HIV-1 and cocaine. Astrocytes, integral components of the CNS, are reported to be susceptible to HIV-1 infection. Upon activation, astrocytes release a number of immunoregulatory products that foster the immunopathogenesis of HIV-1 infection. Signal transduction via mitogen-activated protein kinases (MAP kinases) play a significant role in cellular immune responses. The role of cocaine on MAP kinases in the context of susceptibility to HIV-1 infection has not yet been delineated in normal human astrocytes (NHA). Consequently, the following aim is proposed: Cocaine acts as a co-factor in the neuropathogenesis HIV-1 infection. Further, we propose that cocaine mediates these effects by enhancing HIV-1 infection via the modulation of MAP kinases. We also propose to investigate the effect of cocaine on the proteomic profile of un-infected and HIV-1 infected NHA. Elucidating the molecular mechanisms of cocaine- mediated enhancement of HIV-1 infection in NHA that lead to HIV-1 disease progression and the identification of associated unique proteins may help to develop novel therapeutic strategies in drug using HIV-1 infected subjects.

描述（由申请人提供）：2003年，估计有230万美国人是可卡因使用者。美国目前正在经历与HIV-1感染纠结的可卡因使用流行。中枢神经系统（CNS）是HIV-1和可卡因的常见靶标。据报道，星形胶质细胞是中枢神经系统的积分成分，容易受到HIV-1感染的影响。激活后，星形胶质细胞释放了许多免疫调节产物，以促进HIV-1感染的免疫发作。通过有丝分裂原激活的蛋白激酶（MAP激酶）在细胞免疫反应中起重要作用。在正常的人类星形胶质细胞（NHA）中，尚未描述可卡因在对HIV-1感染易感性感染易感性的背景下的作用。因此，提出了以下目的：可卡因是神经病发生HIV-1感染中的共同因素。此外，我们建议可卡因通过通过MAP激酶的调节增强HIV-1感染来介导这些作用。我们还建议研究可卡因对未感染和HIV-1感染NHA的蛋白质组学特征的影响。阐明可卡因介导的NHA中HIV-1感染增强的分子机制，从而导致HIV-1疾病进展并鉴定相关的独特蛋白质可能有助于使用HIV-1感染受试者在药物中开发新的治疗策略。