Understanding Immunopathogenesis of Hepatitis B Virus

乙肝病毒是一种肝炎病毒，是人类急性和慢性肝炎的主要原因。 全球有3亿人慢性感染乙肝病毒，使其成为全球感染乙肝病毒最多的国家之一。 人类常见的病原体。 乙肝病毒的复制不是细胞病变，而且有证据表明肝脏的病理是由免疫介导的。 因此，了解急性和慢性乙肝病毒感染的发病机制是必要的 了解这些过程背后的免疫反应。发生自然的肝炎病毒感染 仅限于人类和其他免疫系统特征不佳且难以识别的远交物种 学习。 这项提议寻求使用一种新的乙肝病毒感染转基因小鼠模型来识别 急性和慢性乙肝病毒感染的免疫发病机制包括 了解先天免疫反应在这些疾病过程中的作用。我们希望在 识别这些疾病过程的潜在机制，我们将能够设计出特定的 预防和治疗乙肝病毒相关性肝病的免疫疗法。我们的具体目标是：1.确定 非经典NKT细胞在我们转基因小鼠体内介导急性实验性肝炎的机制 2.验证非经典NKT细胞早期激活的假说 和/或NK细胞在我们的原发性乙肝病毒感染模型中可以显著影响慢性期 我们的疾病模型中的肝炎；以及3.建立体外非经典NKT细胞激活模型 对乙肝病毒的反应，这将建立一个基本的实验系统来识别 非经典NKT细胞激活机制。

Hepatitis B Virus (HBV)is a hepadnavirus that is a major cause of acute and chronic hepatitis in humans. Three hundred million people globally are chronically infected with HBV, making HBV one of the most common human pathogens. HBV replication is not cytopathic, and evidence has shown that hepatic pathology is immune-mediated. Thus, understanding the pathogenesis of acute and chronic hepatitis B virus infection mandates understanding the immune responses underlying these processes. Natural hepadnaviral infections occur only in humans and other outbred species whose immune systems are poorly characterized and difficult to study. This proposal seeks to use a new transgenic mouse model of hepatitis B virus infection to identify mechanisms involved in immunopathogenesis of acute and chronic hepatitis B virus infection, including understanding the role of the innate immune response in these disease processes. It is our hope that in identifying mechanisms underlying these disease processes, we will be able to design specific immunotherapies to prevent and treat HBV-related liver disease. Our specific aims are: 1. To determine the mechanism by which non-classical NKT cells mediate acute experimental hepatitis in our transgenic mouse model of primary HBV infection; 2. To test the hypothesis that the early activation of non-classical NKT cells and/or NK Cells in our model of primary HBV infection can significantly influence the chronic phase of hepatitis in our disease model; and 3. To develop an in vitro model of non-classical NKT cell activation in response to Hepatitis B virus, which will establish a fundamental experimental system for identifying the mechanisms of non-classical NKT cell activation.