Abstract：
Due to the limited host range of HBV, research progress has been hindered by the absence of a suitable animal model. The natural history of woodchuck hepatitis virus (WHV) infection in woodchuck closely mirrors that of HBV infection in human, making this species a promising candidate for establishing both in vivo and in vitro HBV infection models. Therefore, this animal may be a valuable species to evaluate HBV vaccines and anti-HBV drugs. A significant milestone in HBV and hepatitis D virus (HDV) infection is the discovery of sodium taurocholate cotransporting polypeptide (NTCP) as the functional receptor. In an effort to enhance susceptibility to HBV infection, we introduced hNTCP into the woodchuck hepatocytes by multiple approaches including transduction of vLentivirus-hNTCP in woodchuck hepatocytes, transfection of p-lentivirus-hNTCP-eGFP plasmids into these cells, as well as transduction of vAdenovirus-hNTCP-eGFP. Encouragingly, our findings demonstrated the successful introduction of hNTCP into woodchuck hepatocytes. However, it was observed that these hNTCP-expressing hepatocytes were only susceptible to HDV infection but not HBV. This suggests the presence of additional crucial factors mediating early-stage HBV infection that are subject to stringent species-specific restrictions.
摘要：
由于HBV的宿主范围有限，缺乏合适的动物模型阻碍了研究进展。土拨鼠肝炎病毒（WHV）感染的自然历史，使该物种成为建立体内和体外HBV感染模型的有希望的候选者。因此,这种动物可能是评估HBV疫苗和抗HBV药物的有价值的物种。HBV和丁型肝炎病毒（HDV）感染的一个重要里程碑是牛磺胆酸钠协同转运多肽（NTCP）作为功能受体的发现。在努力提高对HBV感染的易感性，我们通过多种方法将hNTCP引入土拨鼠肝细胞，包括在土拨鼠肝细胞中转导vLentivirus-hNTCP，将p-慢病毒-hNTCP-eGFP质粒转染到这些细胞中，以及vAdenovirus-hNTCP-eGFP的转导。令人鼓舞的是，我们的发现证明了hNTCP在土拨鼠肝细胞中的成功导入.然而,观察到这些表达hNTCP的肝细胞仅对HDV感染敏感，而对HBV不敏感。这表明存在介导早期HBV感染的其他关键因素，这些因素受到严格的物种特异性限制。
