Immune System Modeling/HIV

抗逆转录病毒治疗开始后血浆HIV-1病毒载量下降的数学分析 对HIV-1感染的动态有了一些重要的见解，但没有治愈。模特， 再加上对临床数据的分析，表明通过100%有效的治疗，艾滋病毒可以从 短寿命和长寿命的生产性感染细胞种群。在这里，我们建议研究一组 与根除艾滋病毒遇到的障碍有关的问题和发展 有效的艾滋病毒疫苗。我们将通过组合建模和协作来实现这些目标 试验组。特别是，我们计划继续开发新的病毒动态模型和使用 他们分析动物和患者的数据。目前的HIV/SIV模型在以下方面做得非常糟糕 实事求是地描述，宿主的免疫反应。在以前工作的基础上，我们计划开发 同时包含对HIV的溶细胞性和非溶细胞性CD8反应的模型。有了疫苗试验数据， 我们将观察抗原特异性CD8细胞水平升高对后续动力学的影响。 病毒在SIV/SIV挑战中的增长。我们将模拟挑战剂量的影响，并检查 为什么低剂量的挑战通常不会导致感染。天然抗体或其他先天抗体 机制可能在这里起作用，我们将把抗体反应合并到初次感染中。 模特们。还将探索其他领域，如肠道相关淋巴组织的感染、 细胞被繁殖感染的可能性，以及潜伏水库的稳定性问题。

The mathematical analysis of plasma HIV-1 viral load decay after the initiation of antiretroviral therapy has led to a number of important insights about the dynamics of HIV-1 infection, but not to a cure. Modeling, coupled to analysis of clinical data, suggested that with 100% effective therapy HIV could be eliminated from both short- and long-lived productively infected cell populations. Here, we propose to examine a set of problems related to the hurdles that have been encountered to eradicating HIV and thee development of effective HIV vaccines. We will pursue these ends by a combination of modeling and collaboration with experimental groups. In particular, we plan to continue to develop new viral dynamic models and use them to analyze both animal and patient data. Current HIV/SIV models have done a very poor job of realistically describing, the host immune response. Building on previous work, we plan to develop models that incorporate both cytolytic and noncytolytic CD8 responses to HIV. With vaccine trial data, we will look at the effects of elevated levels of antigen specific CD8 cells on the subsequent dynamics of viral growth upon SHIV/SIV challenge. We will model the effects of challenge dose and examine the reason why low-dose challenge frequently does not lead to infection. Natural antibody or other innate mechanisms may be at play here, and we will incorporate antibody responses into primary infection models. Other areas also will be explored such as Infection of gut associated lymphoid tissue, the possibility of cells being multiply infected, and issues of the stability of the latent reservoir.