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

为了分析乙型肝炎病毒前孔蛋白和e抗原的功能，采用鸭乙型肝炎病毒（DHBV）感染实验，探讨了前孔突变体的可复制性和发病机制。将克隆的2株野生型和6株前缺陷突变型DHBV DNA转染鸭肝脏，比较病毒的感染性和血清和肝脏中病毒核酸的含量。接种14 d时，野生型和前突变体的传染性分别为100%和55%，前突变体携带者血清中DHBV DNA含量低于野生型。同时感染野生型和前体细胞突变型DHBV导致野生型病毒血症，表明前体细胞蛋白可能促进病毒复制。野生型慢性感染表现为病毒血症滴度高，肝脏组织学变化不大，而前突变体的复制受到抑制，肝细胞坏死和小叶内淋巴细胞浸润。接种6周时，野生型和pre -突变型携带者的所有肝细胞均检测到DHBc抗原表达，接种20周时，pre -突变型携带者的肝细胞中DHBc抗原表达量较少。慢性DHBV前突变体感染伴免疫反应和病毒复制抑制。必须对病毒相关蛋白进行精确的研究，以阐明前突变体的发病机制。

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.