SIV & HIV 1 RECOMBINANTS SHIV SUBTYPE E ENV

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。 未来方向 在猕猴中限制SHIV-Thai-E的病毒复制步骤 细胞将通过生物化学方法进行定义;重点是病毒体 连接、辅助受体使用和融合进入。 猕猴会 接种SHIV-CAR-E，以确定这种嵌合病毒是否 确定持续感染和（潜在）原因 免疫缺陷病 关键词SHIV，疫苗

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