HEPATITIS-B VIRUS (HBV) PRECORE PROTEIN INHIBITS HBV REPLICATION IN TRANSGENIC MICE

In this study, we examined the ability of the hepatitis B virus (HBV) precore, envelope, and X gene products to modulate HBV replication in the livers of transgenic mice that replicate the virus, Hepatic HBV re plication was not affected by overexpression of the envelope or X gene products when these animals were crossed with transgenic mice that ex press the corresponding viral genes in the hepatocyte. Overexpression of the precore protein, however, eliminated nucleocapsid particles fro m the cytoplasm of the hepatocytes and abolished HBV replication witho ut affecting the hepatic steady-state content of pregenomic HBV RNA, T hese observations suggest that the precore protein can exert a dominan t negative effect on HBV replication, presumably at the level of nucle ocapsid particle maturation or stability, suggesting an important role for this enigmatic viral protein in the HBV life cycle.