HIV NEF FUNCTION

HIV NEF 功能

• 批准号: 6111169
• 负责人: Jon W Marsh
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6111169
• 关键词: HIV infections; T lymphocyte; gene expression; host organism interaction; human immunodeficiency virus 1; human tissue; immunopathology; intracellular; leukocyte activation /transformation; macrophage; protein kinase; virus infection mechanism; virus protein

The objective of this study is to elucidate the intracellular interactions of the HIV regulatory protein Nef with host cell activities. Early in the HIV-1 infection of CD4 T cells this retrovirus expresses regulatory proteins, with the Nef transcript representing nearly 80% of total viral mRNA. In vivo infectivity by SIV and HIV is achieved in the absence of Nef expression, but there is an absolute requirement for Nef in the production of high viral titers. In the absence of Nef, there is loss of development of the immunological and neurological dysfunctions characteristic of AIDS. The essential activity of the Nef protein in the development of AIDS has not been defined. We have discovered that expression of Nef in human CD4 T cells results in a lowering of the activation threshold. Since activation is essential for viral synthesis, Nef thus has a direct role in increasing viral production. Evidence suggests that the biochemical site affected by Nef is early in the T cell receptor pathway. We had previously established that the Nef protein associates with a member of the p21-activated kinase (PAK) family, which is known to initiate activation pathways as well as alter cytoskeletal structures. An understanding of the biochemical activity of this virulence factor could lead to new options for treating HIV-infected individuals.

本研究的目的是阐明 HIV 调节蛋白 Nef 与细胞内的相互作用 宿主细胞活动。在 HIV-1 感染早期，CD4 T 细胞 逆转录病毒表达调节蛋白，带有 Nef 转录本 占病毒总mRNA的近80%。体内传染性 SIV和HIV是在Nef表达缺失的情况下实现的，但是 在高品质的生产中对Nef有绝对的要求 病毒滴度。如果缺乏 Nef，就会丧失发育能力。 免疫学和神经学功能障碍的特征 艾滋病。 Nef 蛋白在发育过程中的基本活性 艾滋病的定义尚未明确。我们发现了这个表达式 人类 CD4 T 细胞中的 Nef 会导致活化降低 临界点。由于激活对于病毒合成至关重要，因此 Nef 对增加病毒产量有直接作用。有证据表明 受 Nef 影响的生化位点位于 T 细胞的早期 受体途径。我们之前已经确定 Nef 蛋白质与 p21 激活激酶的成员相关 (PAK) 家族，已知其启动激活途径为 以及改变细胞骨架结构。的理解 这种毒力因子的生化活性可能会导致新的 治疗艾滋病毒感染者的选择。