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

为分析B肝炎病毒前C蛋白和e抗原的功能，对鸭B肝炎病毒（DHBV）进行了实验感染，研究了DHBV前C突变株的复制能力和致病性。比较病毒的感染性及血清和肝脏中病毒核酸的含量。接种14 d时，野生型和前C区突变型的感染率分别为100%和55%，前C区突变型携带者血清中DHBV DNA含量低于野生型。野生型和前C区突变型DHBV共感染导致野生型病毒血症，表明前C区蛋白可能促进病毒复制。野生型慢性感染后，病毒血症滴度高，肝组织学改变轻微，而前C区突变体病毒复制受到抑制，肝细胞坏死，小叶内淋巴细胞浸润。接种后6周，野生型和前C区突变型携带者肝细胞内均检测到DHBc抗原表达，而前C区突变型携带者在接种后20周，仅在少数肝细胞内检测到少量DHBc抗原表达，慢性DHBV前C区突变型感染伴随免疫反应和病毒复制抑制。因此，必须对病毒相关蛋白进行精确的研究，以阐明前C区突变体的发病机制。

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.