Different antibody responses against hepatitis B surface antigen among mouse strains transfected with mutant viral DNA

Rapid seroconversion from hepatitis B surface antigen (HBsAg) to anti-HBs antibody is seen in most patients with fulminant hepatitis B. It is unclear whether viral mutation or host immune background is responsible for such enhanced host reaction to hepatitis B virus (HBV). To investigate interaction between virus mutation and host immune background, we established a mouse model of hepatitis B using liposome-mediated gene transfer. A mixture of liposomes and full-length viral DNA derived from hepatitis B patients was injected into three strains of purebred mice intrahepatically. After injection, HBsAg and antibody in liver and serum were serially measured. Three days after transfection, viral transcript and antigen were detected in the liver and serum. Ten days after transfection with wild-type DNA, hepatitis B surface antibody was detectable in two of the three strains. Mice that did not produce antibody after transfection with wild-type DNA produced a high amount of serum antibody against surface antigen when transfected with fulminant hepatitis-associated DNA. The present results are consistent with previous clinical observations of rapid HBsAg seroconversion in patients with fulminant hepatitis B. Further studies are needed to determine which mutations are responsible for differences in immunogenicity between HBV strains.