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The core gene of the hepatitis B virus genome contains two conserved in-phase initiation codons separated by about 90 nucleotides. This region ("the precore region") encodes largely hydrophobic amino acids. We have expressed the coding sequence of the core gene with or without the precore region by using a simian virus 40-derived vector in heterologous mammalian cells. The results show that the precore region is not required for the expression either of core antigen (cAg) or of a related hepatitis B virus antigen, the e antigen (eAg). However, the precore region causes the cAg to become associated with cytoplasmic membranes, probably the endoplasmic reticulum. Further, the presence of the precore sequence results in the secretion of eAg. Our results suggest that the precore region plays a role in targeting core proteins to the membrane; this may be the direct cause of eAg secretion and also may aid in the interaction of the core and surface antigens in the formation of the viral particle.

Hepatitis B virus gene function: the precore region targets the core antigen to cellular membranes and causes the secretion of the e antigen.