SIV & HIV 1 RECOMBINANTS SHIVNEF

意义重组SHIV克隆是检测HIV-1的一种手段 nef基因在体内用于控制病毒载量和进展的功能 恒河猴的艾滋病 针对以下疾病的新型抗病毒疗法 HIV-1 Nef可以在SHIVnef猴模型中进行测试。 目标和 研究HIV-1感染和艾滋病发病机制的动物模型是 不可用. 为了分析HIV-1特异性基因在体内的功能， SIV/HIV-1重组病毒（SHIV）已被构建 通过用对应物替换致病性克隆SIVmac 239中的基因， HIV-1基因。 我们已经制备了含有各种HIV-1 nef的SHIV克隆， 基因来研究nef在体内的功能。 结果HIV-1-SF 2和 用HIV-1-SF 33 nef基因替换HIV-1-SF 33 nef基因。 SIVmac 239克隆。 两只幼年恒河猴接种了 SHIV-SF 2nef在感染急性期表现出低病毒载量， 在慢性阶段;这些动物健康了两年多。 另外两只幼年猕猴接种SHIV-SF 33 nef。 这些动物中有一只保持低病毒载量超过两年。 相比之下，第二只动物在约6 几个月后，一个人患上了致命的艾滋病样疾病， 感染后一年。 从该动物中回收病毒， 尸检并命名为SHIV-SF 33 nefA。 序列分析表明， 病毒揭示了nef相对于 输入病毒克隆中的nef序列。 今后的方向 确定适应病毒SHIV-SF 33 nefA的致病潜力 将被接种到健康的未暴露的幼年猕猴中。 这些 将监测动物的病毒载量和 免疫缺陷病 基因内SHIV-SF 33 nefA重组体和 将构建涉及HIV-1-SF 33 nef基因的点突变体 为了确定哪种序列变化导致病毒适应， 和发病机制。 关键词SHIV，抗病毒

Significance Recombinant SHIV clones are a means to examine HIV-1 nef gene function in vivo for control of virus load and progression to simian AIDS in rhesus macaques. Novel antiviral therapies against HIV-1 Nef could be tested in the SHIVnef monkey model. 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 various HIV-1 nef genes to study nef function in vivo. Results The HIV-1-SF2 and HIV-1-SF33 nef genes were used to replace the nef gene of the SIVmac239 clone. Two juvenile rhesus macaques inoculated with SHIV-SF2nef showed low virus load in the acute stage of infection and in the chronic stage; these animals were healthy for over two years. Two additional juvenile macaques were inoculated with SHIV-SF33nef. One of these animals has maintained low virus load for over two years. In contrast, the second animal showed a rise in virus load at about 6 months and subsequently developed a fatal AIDS-like disease by one year after infection. Virus was recovered from this animal at necropsy and designated SHIV-SF33nefA. Sequence analysis of this virus revealed about 8 amino acid changes in nef relative to the sequence of nef in the input viral clone. Future Directions To determine the pathogenic potential of the adapted virus, SHIV-SF33nefA will be inoculated into healthy unexposed juvenile macaques. These animals will be monitored for virus load and clinical signs of immunodeficiency disease. Intragenic SHIV-SF33nefA recombinants and point mutants, involving the HIV-1-SF33 nef gene, will be constructed to determine which sequence change(s) accounts for viral adaptation and pathogenesis. KEYWORDS SHIV, antiviral