EVALUATION OF SIV EXPRESSING IGIF

恒河猴SIV感染是HIV最好的动物模型 感染和艾滋病。 在这种动物模型中的研究 证明了nef基因在发病机制中的重要性。 感染携带nef基因缺失的SIVmac 239的猕猴 （SIVDnef）在感染后保持健康超过3年; 此外，动物被保护免受高剂量的 毒SIVmac 251。 综合这些SIVDnef的评估， 体内支持这种病毒是一种活的候选者的概念， 减毒疫苗 然而，这种病毒无限期存在于 猕猴，在接种疫苗后一年内没有保护作用， 致病性，因此限制了其作为 疫苗 干扰素-γ诱导因子（IGIF）是近年来发现的一种新的抗肿瘤因子， 发现了诱导IFN-γ，GM-CSF， 降低IL-10的产生并激活NK细胞。 这些 发现和观察，小鼠IGIF选择性激活TH- 1克隆，指出了1型免疫反应的可能性。 的 研究者先前构建了重组SIVmac 239克隆 nef缺失并表达IFN-g（SIVHyIFN）， 证明了与SIVDnef相比，这种病毒产生了一种 减少幼年猕猴的病毒载量， 对强毒SIVmac 251攻击的抗性。 而且他们 表明该病毒对新生猕猴没有致病性。 现在，他们已经克隆了猕猴IGIF基因，并构建了一个 携带该基因的重组病毒（SIVHyIGIF）。 本 研究者希望研究病毒学和免疫学的建议 IGIF表达在逆转录病毒感染中的作用， 疫苗在猕猴中的潜在用途。 这些实验可以提供 有更多证据支持免疫系统 可以通过提供适当的细胞因子来调节以抵抗损伤 在正确的时间。

SIV infection of rhesus macaques is the est animal model for HIV infection and Aids in humans. Studies in this animals model have demonstrated the importance of the nef gene in pathogenesis. Macaques infected with SIVmac239 carrying a deletion in the nef gene (SIVDnef) remained healthy for more than 3 years after infection; in addition animals were protected against challenge with high doses of virulent SIVmac251. Taken together these assessments of SIVDnef in vivo support the notion that this virus is a candidate for a live attenuated vaccine. However, this virus persists indefinitely in macaques, does not protect under one year post-vaccination and is pathogenic to enonates, therefore limiting its potential use as a vaccine. Interferon-gamma inducing factor (IGIF) is a recently discovered cytokine that induces the production of IFN-g, GM-CSF, decreases the production of IL-10 and activates NK ells. These findings and the observation that murine IGIF selectively activates TH- 1 clones, points to the possibility of a Type-1 immune response. The investigator previously constructed a recombinant SIVmac239 clone with a deletion in nef and expressing IFN-g (SIVHyIFN) and demonstrated that compared to SIVDnef, this virus generated a reduced virus load in juvenile macaques and conferred greater resistance to challenge with virulent SIVmac251. Moreover, they demonstrated that this virus was not pathogenic to neonatal macaques. Now they have cloned the macaque IGIF gene and constructed a recombinant virus that carries this gene (SIVHyIGIF). In the present proposal the investigator wishes to study the virologic and immunologic effects of IGIF expression in the context of a retroviral infection and potential vaccine use in macaques. These experiments may provide additional evidence to support the hypothesis that the immune system can be regulated to fight insults by providing the appropriate cytokines at the right times.