Reservoir modulation by Nef and anti-nef CTL

项目摘要/摘要 艾滋病毒已被证明是非常熟练的，几乎避免了所有治愈的尝试，只有一种，也可能有两种 到目前为止已成功治愈的个人。需要更多更好的想法来开发新的治疗方法 战略。这些策略的创建依赖于对宿主和病毒因素的更好了解 规定储存库的大小、位置以及免疫反应和治疗的逃避。在这里，我们将评估 病毒Nef蛋白在建立和维护SIV感染者SIV储存库中的重要性 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 在保护潜伏感染细胞免受抗病毒免疫反应的影响方面，效果更好或更差。在目标2中，我们将感染 携带Nef突变病毒或野生型的猕猴，将它们放入抑制性手推车治疗，并 从大小、位置、病毒表达和病毒序列进化等方面全面评估储存库。 这些研究将对评估靶向Nef蛋白的新疗法(通过 疫苗接种或药理作用)在推进根除战略方面可能卓有成效。

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.