CELLULAR TROPISM OF A BRAIN DERIVED HIV-1 ISOLATE

脑源性 HIV-1 分离株的细胞趋向性

• 批准号: 2065296
• 负责人: William D. O'Brien
• 金额: $ 10.43万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-07-01 至 1995-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2065296
• 关键词: AIDS; genetic manipulation; genetic mapping; genetic strain; host organism interaction; human immunodeficiency virus 1; human tissue; macrophage; monoclonal antibody; nervous system infection; nucleic acid sequence; polymerase chain reaction; site directed mutagenesis; virus replication

Neurologic impairment is now a well-recognized symptom of the acquired immunodeficiency syndrome (AIDS); many of the central nervous system (CNS) abnormalities appear to be a direct result of infection of cells of the mononuclear phagocyte lineage by human immunodeficiency virus type 1 (HIV- 1). These cells are susceptible to productive infection by some but not all HIV-1 isolates. It is of importance to identify the viral function(s) responsible for the observed differences in HIV-1 cellular tropism. The overall goal of the proposed research is to understand the mechanism of HIV-1 tropism for mononuclear phagocytes. REplication of a cloned macrophage-tropic cells, reverse transcription, integration, and virus- specific RNA production in peripheral blood lymphocytes and mononuclear phagocytes. These properties will be compared with those of HIV-1 isolates having differing abilities to productively infect mononuclear phagocytes in order to identify the stages of the HIV-1 life-cycle blocked in infection with non-tropic isolates (Aim 1). To identify viral genes or sequences responsible for mononuclear phagocyte tropism, molecular recombinants will be constructed between cloned isolates with differing abilities to replicate in these cells (Aim 2). Preliminary experiments using parental and recombinant HIV-1 strains suggest that HIV-1 strains unable to productively infect mononuclear phagocytes appear to be blocked at entry. Binding and penetration assays (Aim 3) will be used to delineate how entry is involved in infection with strains poorly tropic for mononuclear phagocytes. An understanding of precise viral mechanisms for tropic effects of HIV-1 in mononuclear phagocytes will suggest strategies to interfere with virus replication in these cells. Studies such as these may allow one to interfere with the entry of HIV-1 from the blood into the CNS via mononuclear phagocytes and reach the ultimate goal of reducing the prevalence of neurologic complications of AIDS.

神经系统损害现在是被识别的症状 免疫缺陷综合征（AIDS）；许多中枢神经系统（CNS） 异常似乎是细胞感染的直接结果 人类免疫缺陷病毒1型单核吞噬谱系（HIV- 1）。 这些细胞容易受到某些人的生产感染的影响，但不容易 所有HIV-1分离株。识别病毒功能很重要 负责观察到的HIV-1细胞向流差异。 拟议研究的总体目标是了解 单核吞噬细胞的HIV-1向流。 克隆的复制 巨噬细胞，逆转录，整合和病毒 - 外周血淋巴细胞和单核中的特定RNA产生 吞噬细胞。 这些特性将与HIV-1分离株的特性进行比较 在有效地感染单核吞噬细胞中具有不同的能力 为了识别感染中阻塞的HIV-1生命周期的阶段 与非热带分离株（AIM 1）。 鉴定病毒基因或负责单核吞噬细胞的序列 对流，分子重组将在克隆的分离株之间构建 在这些细胞中复制的能力不同（AIM 2）。 初步的 使用亲本和重组HIV-1菌株的实验表明HIV-1 无法有效感染单核吞噬细胞的菌株似乎是 入口被阻止。 绑定和穿透分析（AIM 3）将用于 描述进入如何参与感染的菌株感染不佳的菌株 单核吞噬细胞。 对HIV-1在热带影响中的精确病毒机制的理解 单核吞噬细胞将提出干扰病毒的策略 这些细胞中的复制。 诸如此类的研究可能会使 干扰HIV-1从血液进入中枢神经系统的进入 单核吞噬细胞并达到减少的最终目标 艾滋病神经系统并发症的患病率。