SIV & HIV 1 RECOMBINANTS SHIVSUBTYPE B ENV

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 重组病毒克隆。目的用动物模型研究这两种疾病 HIV-1感染和艾滋病发病机制尚不清楚。要分析 HIV-1特异性基因在体内的功能，SIV/HIV-1重组 病毒(命名为SHIV)是通过将基因替换为 含有HIV-1基因的致病克隆SIVmac239。我们有 构建含不同类型HIV-1囊膜基因的SHV克隆 B亚型分离株，并对这些重组病毒进行了分析 幼年猕猴和新生猕猴体内。结果A致病志贺病病毒 (命名为Shiv-33A)，含有HIV-1-SF33的env基因， 通过幼年恒河猴的一段话获得。SIV-33A 在幼年猕猴中产生猿猴艾滋病时， 静脉或粘膜(口腔和阴道粘膜)途径。在……里面 此外，新生的猕猴(2天大)也患上了猿猴艾滋病 在静脉接种后。猪瘟病毒env基因的序列分析 SIV-33A揭示了大约15个氨基酸相对于输入的变化 SHIV-33克隆株。所有表现出免疫缺陷疾病的动物也 表现出CD4T细胞的快速和持续下降 外周血和淋巴结。基因内的未来方向 涉及HIV-1SF33包膜的SIV-33重组体和点突变体 基因，将被构建以确定哪个序列改变(S) 解释了病毒适应和发病机制。研究也将是 以确定CD4T细胞快速耗竭的机制 在感染致病性SHV-33A毒株的急性期； 这种耗尽可能是由于病毒的直接细胞病变效应 或间接机制涉及细胞因子的改变。 主持人。希沃克病毒，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 viral 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-B isolates, and have analyzed these recombinant viruses in vivo in juvenile and newborn macaques. Results A pathogenic SHIV (designated SHIV-33A), containing the env gene of HIV-1-SF33, was obtained by one passage in a juvenile rhesus macaque. SHIV-33A produced simian AIDS in juvenile macaques when given by either the intravenous or mucosal membrane (oral and vaginal mucosa) routes. In addition, newborn macaques (2 days of age) also developed simian AIDS after intravenous inoculation. Sequence analysis of the env gene of SHIV-33A revealed about 15 amino acid changes, relative to the input SHIV-33 clone. All animals showing immunodeficiency disease also exhibited a rapid and sustained decline in CD4 T-cells in both peripheral blood and lymph nodes. Future Directions Intragenic SHIV-33 recombinants and point mutants, involving the HIV-1SF33 env gene, will be constructed to determine which sequence change(s) accounts for viral adaptation and pathogenesis. Studies will also be performed to determine the mechanism of rapid depletion of CD4 T-cells in the acute stage of infection with the pathogenic SHIV-33A strain; this depletion may be due to either direct cytopathic effects of virus or to indirect mechanisms involving alterations in cytokines in the host. KEYWORDS SHIV, vaccine