甲型肝炎病毒属于小核糖核酸病毒科肝炎病毒属，是导致急性甲型肝炎最主要的病原体。全球每年仍然有140万甲型肝炎病毒 (HAV) 的感染病例，主要爆发于发展中国家。甲型肝炎病毒作为小RNA病毒科中较为特殊的种属，与其他的小RNA病毒有较大不同：甲型肝炎病毒具有极强的稳定性，能够耐酸、耐碱、耐高温，在水源中能够存活数月之久，可通过污染水源、食物、海产品等的传播造成甲型肝炎散发性流行或大流行。本研究拟通过解析甲型肝炎病毒与其中和性单克隆抗体可变区复合物的精细三维结构，鉴定抗体识别甲型肝炎病毒的确切位点，揭示抗体中和病毒的免疫机制，从而为抗甲型肝炎病毒药物的研发提供理论依据。同时开展甲型肝炎病毒两种不同生命周期的病毒颗粒的免疫原性研究，为新型高效疫苗的开发提供质量控制参考标准。

Hepatitis A virus, belonging to the family of Picornaviridae and genus Hepatovirus, is the major causative agent of Hepatitis A, which is a global health problem. Approximately 1.4 cases of hepatitis A have been reported annually. HAV has radically different properties from those of other picornaviruses, eg. robust stability, resistant to acid (pH 1), alkaline (pH 10) and high temperature (up to 70℃), can survive for months in water. The hepatitis A virus is transmitted through ingestion of contaminated food and water, causing sporadic and epidemic diseases. In this study, we will determine the three-dimensional structures of HAV and Fab fragments of its neutralizing mAb complex to identify the accuracy mAb binding sites, which elucidates the molecular mechanism of protection by antibodies. Meanwhile, we also explore the immunogenic differences between HAV natural empty particles and mature virons. These results will provide the great potential to discover the antiviral therapeutics against HAV.