Translational Selection in the Expression of the Hepatitis B Virus Envelope Proteins

The region of the hepatitis B virus (HBV) genome coding for the viral envelope proteins contains three inphase ATGs that are conserved among viral subtypes. Each of these ATGs can be used as mRNA initiation codons. The three translated proteins share a carboxy-terminal region (the S protein) and extend amino-terminally to include the pre-S2 region in the middle (M) protein, and the pre-Sl and pre-S2 regions in the large (L) protein. We have inserted the HBV DNA coding for the M protein into a baculovirus expression vector. Infected insect cells transcribe a mRNA that is initiated solely within a baculovirus promoter, and that contains the initiator codons for both M and S proteins. Although these cells primarily secrete the M protein, the major translational product is the S protein, which is not secreted. This preferential translation, the result of the use of an internal initiator codon, demonstrates that the regulation of HBV envelope protein production can occur at the translational level.