MODELING VIRAL AND T LYMPHOCYTE DYNAMICS

描述：数学建模与实验相结合， 提高对艾滋病毒感染过程的认识， 人类和改进疗法的发展。然而，艾滋病毒并没有 从感染者和各种宿主中根除， 潜伏感染的细胞，毛囊树突状细胞（FDC）上捕获的病毒， 精液中的病毒已经被确认。本申请建议继续 开发更现实的艾滋病毒感染模型， 强调发生在淋巴组织中的事件。申请人建议 开发明确考虑血液感染的模型， 组织，FDC的作用，以及药物可能不完全渗透到 各种细胞群和组织。艾滋病毒对健康的主要影响 感染是CD4+ T细胞耗竭的结果。但 体内T细胞的群体动力学特征不佳。拟 发展理论和分析体内标记研究的数据， 表征未感染的T细胞的增殖和死亡速率， 艾滋病毒感染者和正在接受强效抗逆转录病毒治疗的艾滋病毒感染者 治疗丙型肝炎病毒（HCV）和B肝炎病毒（HBV）感染 在许多感染者中继续引起肝衰竭和肝细胞癌 个体这些药物的抗病毒治疗落后于药物的发展， 艾滋病。申请人建议使用他们所使用的建模和分析工具， 已经开发了用于HIV的药物，以增加对HCV体内动力学的理解 和HBV感染以及抗病毒治疗的效果。除了获得 基本理解，这种方法旨在将信息转化为实际的 环境，申请人希望在设计中与临床小组互动 和评估新的治疗方案。

DESCRIPTION: Mathematical modeling combined with experiment has led to increased understanding of the processes that underlie HIV-1 infection in humans and the development of improved therapies. Nevertheless HIV has not been eradicated from infected individuals and various reservoirs including latently-infected cells, virus trapped on folliculary dendritic cells (FDC), and virus in semen have been identified. This application proposes to continue the development of more realistic models of HIV infection with particular emphasis on events that occur in lymphoid tissue. The applicants propose to develop models that explicitly take into consideration infection in blood and tissue, the role of FDC, and possible incomplete penetrance of drugs into various cell populations and tissues. The primary health-related effects of HIV infection are consequences of CD4+ T cell depletion. Nevertheless, the population dynamics of T cells in vivo are poorly characterized. It is proposed to develop theory and analyze data from in vivo labeling studies that will help characterize the rates of proliferation and death of T cells in uninfected, HIV-infected, and HIV-infected individuals under potent antiretroviral treatment. Infection by hepatitis C virus (HCV) and hepatitis B virus (HBV) continue to cause liver failure and hepatocellular carcinoma in many infected individuals. Antiviral therapy for these agents lags behind developments in HIV. The applicants propose to use the modeling and analysis tools that they have developed for HIV to increase understanding of the in vivo kinetics of HCV and HBV infection and the effects of antiviral therapy. In addition to gaining basic understanding, this approach aims to put information into a practical setting, and the applicants hope to interact with clinical groups in the design and evaluation of new treatment protocols.