Animal model of chronic hepatitis using duck hapatitis B virus precore mutant infection.

为了分析乙肝病毒前C蛋白和e抗原的功能，对鸭乙型肝炎病毒进行了实验性感染，研究了前C基因突变株的复制能力和致病机理，将2株野生型和6株前C基因缺陷突变株的DHBVDNA导入鸭肝脏，比较了病毒的感染性和血清和肝脏中的病毒核酸含量。接种第14天，野毒株和前C区突变株的感染力分别为100%和55%，且前C区突变株携带者的血清DHBVDNA含量低于野生型。野毒株和前C区变异株混合感染可引起野生型病毒血症，提示前C区蛋白可能促进病毒复制。野生型慢性感染病毒滴度高，肝组织学改变轻微，而前C区突变株复制受到抑制，肝细胞坏死，小叶内淋巴细胞浸润。DHBc抗原在接种6周时在野生型和前C区突变携带者的所有肝细胞中均有表达，在接种20周时在少数肝细胞中检测到少量DHBc抗原。慢性DHBV型前C区感染伴随免疫反应和病毒复制的抑制。为了弄清前C区突变的发病机制，必须对病毒相关蛋白进行精确的研究。

To analyze the function of precore protein and e antigen of hepatitis B virus, experimental infection of duck hepatitis B virus (DHBV) was performed and replicability and pathogenesis of precore mutant was investigated.Cloned DHBV DNA of 2 strains of wild type and 6 strains of precore defective mutant were transfected into the duck liver, and infectivity of virus and quantity of viral nucleic acids in the serum and the liver were compared. At 14 days of inoculation, infectivity of wild and precore mutant was 100% and 55%, respectively, and the amount of DHBV DNA in the serum was less in the carriers of precore mutant than wild type. Co-infection of wild and precore mutant DHBV resulted wild type viremia indicating that precore protein might facilitate the viral replication. Chronic infection of wild type showed high titer of viremia and minimal change of liver histology, whereas the replication of precore mutant was suppressed with the histological change of hepatocytes necrosis and intralobular lymphocytes infiltration. DHBc antigen expression was detected in all hepatocytes of wild and precore mutant carriers at 6 weeks of inoculation, and less amount of DHBc antigen in less number of hepatocytes was detected of precore mutant carriers at 20 weeks of inoculation.Chronic DHBV precore mutant infection accompanied with the immunological reaction and the suppression of virus replication. Precise investigation of virus related proteins has to be done to clarify the pathogenesis of precore mutant.