EXPRESSION OF THE HEPATITIS-DELTA VIRUS LARGE AND SMALL ANTIGENS IN TRANSGENIC MICE

Simultaneous infection with hepatitis delta virus (HDV) and hepatitis B virus (HBV) in humans is often associated with severe viral liver di sease including fulminant hepatitis. Since HBV is thought to be noncyt opathic to the hepatocyte, the enhanced disease severity observed duri ng dual infection has been attributed to either simultaneous immune re sponses against the two viruses or direct cytotoxic effects of HDV pro ducts on the hepatocyte or both. To examine these alternate possibilit ies, we Produced transgenic mice that express the small and large delt a antigens (HDAg) in hepatocyte nuclei at levels equal to those observ ed during natural HDV infection. No biological or histopathological ev idence of liver disease was detectable during 18 months of observation , suggesting that neither the large nor small form of HDAg is directly cytopathic to the hepatocyte in vivo.