人类是丙型肝炎病毒（HCV）的唯一天然宿主，对于临床前疫苗保护性评价而言，目前仍然缺乏理想的小动物感染模型。树鼩作为亲缘关系靠近灵长类的小型实验动物可以被HCV偶发性感染，然而即不产生感染性病毒颗粒、也不诱导明显免疫反应的低效复制过程极大地限制了其应用。为了逐步提高HCV对树鼩的适应性，我们成功筛选到能支持HCV完整感染周期的永生化树鼩肝细胞系。据此，本研究拟通过体外适应性传代过程，提升HCV在树鼩肝细胞中的扩增效率，并阐明其适应机制，同时通过转录组比较，发现提供HCV复制条件的关键树鼩宿主因子，最终为HCV在树鼩体内的适应提供条件，以期建立高效感染的HCV树鼩动物模型。该模型的建立不仅可以推进HCV疫苗的研发，同时也将为研究肝脏的抗HCV免疫机制、宿主与HCV的相互作用，HCV的变异规律、免疫逃避策略及致肿瘤机制等研究提供新的平台。

Humans are the only natural hosts of hepatitis C virus (HCV). For preclinical vaccine protection evaluation，a suitable small animal model is still lacking for HCV infection. Tree shrew, a small experimental animal close to primates, has been observed to be an infectable host for HCV, but its use is limited by inefficient replication process that leads to no progeny infectious virus or significant immune response. In order to improve the adaptability of HCV to tree shrews step by step, we established an immortalized tree shrew hepatocyte cell line that can support the complete infection cycle of HCV. Based on this, this project aims to improve the amplification efficiency of HCV in tree shrew hepatocytes by in vitro adaptive passage, and explore the underlying molecular mechanisms. At the same time, through compare of the whole transcriptome, we might find the key host factors supporting HCV replication. Finally, better conditions are provided for adaptation of HCV infection in tree shrew in vivo. There is a great possibility to establish a high-efficient infection tree shrew model for HCV. This small animal model will promote development of Hepatitis C vaccines and opens the opportunity to interrogate hepatic antiviral immunity, host-HCV interactions, viral adaptation, immune evasion strategies and tumorgenesis of HCV at an unprecedented level.