SIV & HIV 1 RECOMBINANTS SHIV SUBTYPE E ENV

SIV

• 批准号: 6277916
• 负责人: PAUL A LUCIW
• 金额: $ 8.13万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6277916
• 关键词: AIDS; Mammalia; Primates; immunology; infection; 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. Future Directions The step in viral replication that resricts SHIV-Thai-E in macaque cells will be defined by biochemical methods; this focus is on virion attachment, coreceptor usage, and fusion entry. Macaques will be inoculated with SHIV-CAR-E to determine whether this chimeric virus establishes persistent infection and (potentially) causes immunodeficiency disease. KEYWORDS SHIV, vaccine

意义重组SHIVenv克隆是一种分析 HIV-1env基因在体内病毒经粘膜传播中的作用 膜和SAIDs致病机制。此外，基于以下因素的疫苗 HIV-1免疫原可以通过挑战这样的 重组克隆。目的建立一种研究HIV-1病毒的动物模型 目前还没有关于感染和艾滋病发病机制的资料。分析功能 体内特异性HIV-1基因、SIV/HIV-1重组病毒 (指定为Shiv)是通过替换 带有相应HIV-1基因的致病克隆SIVmac239。我们已经做出了 含不同HIV-1囊膜(Env)基因的SHIV克隆 恒河猴体内分析的E亚型分离株。结果 含HIV-1-9466分离株env基因的SHIV-TAI-E 泰国，在人和狒狒淋巴细胞中复制，但在 猕猴淋巴细胞。经聚合酶链式反应分析表明，该物种 限制是在病毒复制的早期阶段，在 病毒DNA合成的启动。然而，Shiv-Car-E，包含 非洲HIV-1-CAR402分离株env基因的复制 在人类和猕猴淋巴细胞中都是有效的。未来方向 在猕猴体内重新转录SHV-泰国-E病毒的病毒复制步骤 细胞将由生物化学方法定义；这一重点是病毒粒子 依附，共受体的使用，和融合进入。猕猴将会是 接种SHV-CAR-E以确定该嵌合病毒 确定持续感染和(潜在)原因 免疫缺陷疾病。希沃克病毒，疫苗