宿主体内乙型肝炎病毒的群体动力学模型研究

项目名称： 宿主体内乙型肝炎病毒的群体动力学模型研究

项目编号： No.11271369

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 数理科学和化学

项目作者： 王开发

作者单位： 中国人民解放军第三军医大学

项目金额： 65万元

中文摘要： 乙肝是一种危害极大的传染性疾病，其发病机理与治疗方法已成为基础医学、临床医学等领域关注的焦点，乙肝病毒的感染与复制也已成为传染病动力学的重要组成部分。由于现有的HBV群体动力学模型主要借鉴RNA病毒（如HIV和HCV）的研究成果，而HBV是非细胞毒性DNA病毒，因此现有模型缺乏病毒特异性。本项目将围绕HBV感染与治疗应答的分子生物学机理建立宿主体内病毒群体动力学模型并采集临床数据进行参数估计和校验分析。首先利用动力系统理论和数值计算等手段寻找病毒入侵的阈值，掌握病毒侵入细胞组织的条件和机理；然后结合进化动力学理论研究天然免疫应答、获得性免疫应答和调节性T细胞等的非线性作用规律，探寻HBV感染慢性化的机制；最后分析抗病毒药物作用的动力学模型，量化把握长期用药的可行性和有效性，确定治疗终点的选择时机。成果有助于深入理解病毒致病机理、评价抗病毒方法的疗效，为临床防治提供理论指导和数量依据。

中文关键词： 乙肝病毒；动力学模型；cccDNA；抗病毒治疗；免疫效应

英文摘要： Hepatitis B is a serious infectious disease. Its pathogenesis and treatment have become a focus of attention in the areas of basic medicine, clinical medicine and so on. At the same time, the infection and replication of hepatitis B virus (HBV) have also become an important part in epidemic dynamics. As the current population dynamics model of HBV is based on the researches on RNA viruses (e.g., HIV and HCV), it lacks viral specificity of HBV, which is a noncytopathic DNA virus from the perspective of gene. The present project will construct a series of within-host HBV population dynamics models based on the molecular biological mechanism of HBV infection and treatment response, and collect clinical data for parameter estimation and model assessment. First, based on the theory of dynamic system and the method of numerical calculation, we will determine the threshold of HBV invasion and explore the mechanism of the incursion of HBV. Then, based on the theory of evolutionary dynamics, we will study the in vivo nonlinear interaction networks among the innate immune response, acquired immune response and regulatory T cells, to explore the mechanisms of chronicity of HBV infection. Finally, we will propose and analyse the population dynamics model of HBV under antiviral therapy, expect to quantify the feasibility and

英文关键词： Hepatitis B virus；Dynamic model；cccDNA；Antiviral treatment；Immune response