目前仍缺乏理想的HBV慢性感染动物模型。虽已确认树鼩对HBV易感，但短暂病毒血症后迅速被免疫系统清除。即使未来NTCP转基因动物能感染，也将遇到类似问题。HBV感染的结局取决于抗病毒免疫与病毒免疫抑制之间的平衡，包括HBV在内的许多病毒的生存策略是依靠其免疫抑制功能，本课题设想额外强化HBV的免疫抑制功能，以实现慢性感染。本课题在国家自然科学基金短期资助下成功制备了复制型HBV载体，使得赋予HBV额外免疫抑制功能成为可能。本项目制备3种理论上具有免疫抑制功能的HBV载体（分别表达EB病毒和巨细胞病毒IL-10、仙台病毒C蛋白N端肽），在细胞培养条件下观察其分子生物学和免疫学特性，以筛选出对树鼩具有免疫抑制活性者；利用重组HBV颗粒感染树鼩，观察其慢性HBV感染情况。本研究将提供通用的导致慢性HBV感染的重组HBV，并提供一个慢性HBV感染的小动物模型，将有助于抗HBV药物及疫苗的研发。

Up to now, there is no ideal chronic Hepatitis B virus (HBV) infection animal model available. Although it is confirmed that that tupaia is susceptibile to HBV infection, but HBV is quickly cleared by the immune system after a brief viremia. If HBV could infect the ongoing NTCP transgenic animal model, it will also face such obstacles. The outcome of HBV infection depends on the balance between antiviral immunity and virus immune suppression. The survival strategy for many viruses, including HBV, is dependent on its immune suppression function. The idea of this study is to enhance the immune suppression function of HBV in order to achieve a chronic infection. In the short-term financing of the National Natural Science Foundation of China, we have successfully prepared the replication-competent HBV vector, which makes it possible to endow HBV with additional immune suppression function. In this project, 3 replication-competent HBV vectors with theoretically immune suppression function (expressions of Epstein–Barr virus interleukin 10, Cytomegalovirus IL-10 and the N terminal peptide of Sendai virus C protein) will be constructed on the basis of our replication-competent HBV vector. In cell culture conditions, we will observe their molecular biological and immunological properties, for screening the best one with immunosuppressive activity in tupaia cells. Tupaia with be infected with viral particles derived from the recombinant HBV vectors. Characteristics of tupaia model of chronic HBV infection will be observed. The present study will provide an universal recombinant HBV that leads to chronic HBV infection, and provide a small animal model of chronic HBV infection, which will contribute to the development of anti-HBV drugs and vaccines.