SIV & HIV 1 RECOMBINANTS SHIVSUBTYPE E ENV

SIV

• 批准号: 6116675
• 负责人: PAUL A LUCIW
• 金额: $ 7.98万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6116675
• 关键词: AIDS; Mammalia; communicable diseases; immunology; inflammation; lymphatic system; virus

Significance Recombinant SHIVenv clones are a means to analyze the role of HIV-1 env genes in vivo for viral transmission across mucosal membranes and for SAIDS pathogenesis. Additionally, vaccines based on HIV-1 immunogens can be tested for efficacy by challenge with such recombinant clones. Objectives An animal model to study both HIV-1 infection and AIDS pathogenesis is not available. To analyze function of specific HIV-1 genes in vivo, SIV/HIV-1 recombinant viruses (designated SHIV) have been constructed by replacing genes in the pathogenic clone SIVmac239 with counterpart HIV-1 genes. We have made SHIV clones containing the envelope (env) gene of various HIV-1 subtype-E isolates for analysis in vivo in rhesus macaques. Results SHIV-Thai-E, containing the env gene of the HIV-1-9466 isolate from Thailand, re-plicates in human and baboon lymphocytes but not in macaque lymphocytes. Analysis by PCR revealed that this species restriction is at a step early in viral replication, prior to initiation of viral DNA synthesis. However, SHIV-CAR-E, containing the env gene of the HIV-1-CAR402 isolate from Africa, replicated efficiently in both human and macaque lymphocytes. Juvenile macaques were infected with SHIV-CAR-E by the intravenous and intravaginal (mucosal) route with cell-free virus. These animals exhibited moderate virus loads and produced anti-viral antibodies; no hematologic abnormalities or other disease signs were noted for an observation period of 6 months. Future Directions The step in viral replication that restricts SHIV-Thai-E in macaque cells is being analyzed by biochemical methods; this focus is on virion attachment, co-receptor usage, and fusion entry. A rapid serial passage of SHIV-CAR-E will be performed in juvenile macaques to obtain a pathogenic chimeric virus. KEY WORDS HIV-1 genes, AIDS pathogenesis, SHIV clones FUNDING NIH Grant AI41907

意义重组SHIVenv克隆是一种分析 HIV-1 env基因在体内跨粘膜传播中的作用 膜和SAIDS发病机制。 此外，基于 HIV-1免疫原可以通过用这样的抗体进行攻击来测试功效。 重组克隆。 目的建立一种研究HIV-1的动物模型， 感染和艾滋病发病机制尚不清楚。 分析功能 SIV/HIV-1重组病毒 （命名为SHIV）已经通过替换 致病性克隆SIVmac 239与对应的HIV-1基因。 我们取得了 含有各种HIV-1包膜（env）基因的SHIV克隆 E亚型分离株用于恒河猴体内分析。 结果 SHIV-Thai-E，含有来自HIV-I-9466分离株的env基因， 在人和狒狒淋巴细胞中重复，但在 猕猴淋巴细胞 PCR分析表明，该物种 限制是在病毒复制的早期阶段， 启动病毒DNA合成。 然而，SHIV-CAR-E，含有 来自非洲的HIV-1-CAR 402分离株的env基因， 在人类和猕猴的淋巴细胞中均有效。 幼年猕猴 通过静脉和阴道感染SHIV-CAR-E （粘膜）途径与无细胞病毒。 这些动物表现出 中等病毒载量并产生抗病毒抗体;无 血液学异常或其他疾病体征被记录为 观察期为6个月。 未来的方向病毒的步骤 在猕猴细胞中限制SHIV-Thai-E复制的研究正在进行。 通过生物化学方法进行分析;该焦点在于病毒体附着， 共受体的使用和融合进入。 一种快速连续的 SHIV-CAR-E将在幼年猕猴中进行，以获得 致病性嵌合病毒 关键词HIV-1基因，艾滋病发病机制， SHIV克隆资助NIH Grant AI 41907