EVALUATION OF SIV EXPRESSING IGIF

SIV感染恒河猴是最容易感染HIV的动物模型 人类的感染和艾滋病。在这种动物模型中的研究已经 证实了nef基因在发病机制中的重要性。 携带nef基因缺失的SIVmac239感染猕猴 (SIVDnef)在感染后3年多保持健康； 此外，动物还可以通过高剂量的 毒力强的SIVmac251。综合考虑以下对SIVDnef的评估 Vivo支持这种病毒是一种活的候选病毒的观点 减毒疫苗。然而，这种病毒会无限期地在 猕猴，在接种疫苗后一年内不保护，并且 致病的，因此限制了它作为一种 疫苗。干扰素-γ诱导因子(IGIF)是近年来发展起来的一种 发现了诱导产生干扰素-g，粒-巨噬细胞集落刺激因子， 减少IL-10的产生，激活NK细胞。这些 小鼠IGIF选择性激活TH-2的研究结果及观察 1个克隆，表明有可能产生1型免疫反应。这个 研究人员此前构建了一个重组SIVmac239克隆 在nef中缺失并表达干扰素-g(SIVHyIFN)和 证明与SIVDnef相比，这种病毒产生了 减少幼年猕猴的病毒载量，并赋予更多 对毒力较强的SIVmac251的抗性。此外，他们还 证明该病毒对新生猕猴无致病性。 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)。在现在 研究人员希望研究病毒学和免疫学的建议 IGIF的表达在逆转录病毒感染和 猕猴潜在的疫苗使用情况。这些实验可能会提供 支持免疫系统假设的更多证据 可以通过提供适当的细胞因子来调节以对抗侮辱 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.