Rat as an animal model carrying human hepatitis B virus in hepatocytes

OBJECTIVE: To establish an experimental animal model of rat carrying human hepatitis B virus in the hepatocytes using a simple and reproducible method. MATERIALS AND METHODS: Human serum rich in hepatitis B virus was injected into portal veins and caudalis veins of young male Wistar rats. One and two months after the injection, liver biopsies were done. In situ hybridization and immunohistochemical study of liver specimens were carried out. Sera were also examined for HBV DNA by polymerase chain reaction. RESULTS: All of seven rats in this experiment were HBV DNA and HBV surface antigen (HBsAg) positive in their hepatocytes. Most HBV positive hepatocytes were distributed around the central vein and scattered in the liver lobules, and HBV DNA and HBsAg were located in cytoplasm. HBsAg exists mainly as the forms of diffuses and inclusion body. No hepatocytic damage or inflammation was observed. Neither viremia nor antigenemia was detected. CONCLUSIONS: Our studies showed for the first time that natural human HBV can enter Wistar rat liver cells through intravenous injection efficiently and express for a long period. This animal model can be used in the studies of HBV molecular biology, therapeutic regimens and prophylaxis against HBV. A possible mechanism of HBV entering rat hepatocytes is also proposed.