TRANSMEMBRANE SIGNALING IN HIV INFECTION

HIV 感染中的跨膜信号转导

• 批准号: 3455569
• 负责人: MOSTAFA A NOKTA
• 金额: $ 9.98万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-01-01 至 1995-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3455569
• 关键词: AIDS; AIDS therapy; RNA directed DNA polymerase; T lymphocyte; biological signal transduction; calcium flux; cyclic AMP; cyclic GMP; host organism interaction; human immunodeficiency virus; human subject; human therapy evaluation; immune tolerance /unresponsiveness; interferon gamma; interleukin 2; leukocyte activation /transformation; lymphocyte proliferation; mitogens; phosphatidylinositols; phospholipase C; protein kinase C; second messengers; tissue /cell culture; virus antigen; zidovudine

The aim of this study is to investigate the mechanisms involved in immunologic hyporesponsiveness of lymphocytes from human deficiency virus (HIV) asymptomatic sero-positive, AIDS related complex (ARC) and AIDS, and whether it is due to an alteration in transmembrane signaling in those patients. The biochemical pathways involved in T-cell activation in response to specific and non-specific mitogens will be evaluated in lymphocytes from patients at different stages of infection. The patterns of secondary messenger response (IP3, CA++, cyclic AMP, cyclic GMP) and their relationship to phospholipase C and phosphatidylinositol hydrolysis and activation of protein kinase C will be determined. The relationship between secondary messenger response and immune parameters (including proliferative, interferon-gamma and IL-2 production) of the patients will be studied. The second messenger response will also be studied in a group of AIDS patients before and after 6 months of Zidovudine therapy. Transmembrane signaling in cell line cultures will also be studied in response to HIV infection. This approach will allow rare careful investigation of the effect of HIV on the biochemical pathways involved in transmembrane signaling. Cell lines supporting HIV replication will be used (H-9, MT-4, CEM and U937) and the response of both laboratory and fresh patient virus isolates will be evaluated. Understanding the HIV-induced, intracellular, physiological, and biochemical changes might allow manipulation of these responses to enhance the patient's immune response and the introduction of new anti-HIV agents that could offer novel therapeutic interventions.

本研究的目的是调查涉及的机制 人类缺陷病毒淋巴细胞的免疫反应低下 (HIV) 无症状血清阳性、艾滋病相关综合症 (ARC) 和艾滋病，以及 是否是由于跨膜信号传导的改变所致 患者。参与 T 细胞激活的生化途径 将评估对特定和非特定有丝分裂原的反应 来自不同感染阶段患者的淋巴细胞。图案 第二信使反应（IP3、CA++、环AMP、环GMP）和 它们与磷脂酶 C 和磷脂酰肌醇水解的关系 并确定蛋白激酶C的激活。关系 第二信使反应和免疫参数之间（包括 增殖、干扰素-γ和IL-2的产生）的患者将 被研究。第二信使反应也将在小组中进行研究 艾滋病患者在齐多夫定治疗 6 个月之前和之后的情况。 细胞系培养物中的跨膜信号传导也将在 对艾滋病毒感染的反应。这种方法将允许罕见的小心 研究 HIV 对相关生化途径的影响 跨膜信号传导。将使用支持HIV复制的细胞系 （H-9、MT-4、CEM 和 U937）以及实验室和新鲜的反应 将评估患者病毒分离株。了解艾滋病毒引起的、 细胞内、生理和生化的变化可能允许 操纵这些反应以增强患者的免疫反应 以及新的抗艾滋病毒药物的引入，这些药物可以提供新的 治疗干预。