Reservoir modulation by Nef and anti-nef CTL

项目总结/摘要 艾滋病毒已被证明非常熟练，并避免了几乎所有的治疗尝试，一个，可能两个 迄今为止，已成功治愈的患者。需要更多更好的想法来开发新的治疗方法 战略布局这些策略的创建依赖于对宿主和病毒因素的更好理解， 决定了储库的大小、位置和免疫应答和治疗的逃避。在这里，我们将评估 病毒Nef蛋白在SIV感染者中建立和维持SIV储库的重要性 猕猴在目标1中，我们将使用SIV潜伏期的细胞培养模型来评估Nef的变体是否是 在保护潜伏感染细胞免受抗病毒免疫反应方面更好或更差。在目标2中，我们将感染 携带Nef突变病毒或野生型病毒的猕猴，使动物接受抑制性cART治疗， 在大小、位置、病毒表达和病毒序列进化方面全面评估储库。 这些研究对于评估靶向Nef蛋白的新疗法（通过免疫调节）是否有效将是重要的。 疫苗接种或药物）可能在推进根除战略方面取得成果。

Project Summary/Abstract HIV has proven remarkably adept and avoiding nearly all attempts at a cure, with one and possibly two individuals to date having been successfully cured. More and better ideas are needed to develop novel cure strategies. The creation of these strategies relies on a far better understanding of the host and viral factors that dictate reservoir size, location, and evasion of immune responses and therapeutics. Here, we will assess the importance of the viral Nef protein in establishment and maintenance of the SIV reservoir in SIV infected macaques. In Aim 1, we will use a cell culture model of SIV latency to assess whether variants of Nef are better or worse at protecting latently infected cells from antiviral immune responses. In Aim 2, we will infect macaques with Nef mutant viruses or wild type, place the animals on suppressive cART therapy, and comprehensively assess the reservoir, in terms of size, location, viral expression and viral sequence evolution. These studies will be important in assessing whether novel therapeutics that target the Nef protein (either via vaccination or pharmacological) might be fruitful in eradication strategies moving forward.