POSTTRANSLATIONAL ALTERATIONS IN TRANSMEMBRANE TOPOLOGY OF THE HEPATITIS-B VIRUS LARGE ENVELOPE PROTEIN

The preS domain at the N-terminus of the large envelope protein (LHBs) of the hepatitis B virus is involved in (i) envelopment of viral nucl eocapsids and (ii) binding to the host cell. While the first function suggests a cytosolic location of the preS domain during virion assembl y, the function as an attachment site requires its translocation acros s the lipid bilayer and final exposure on the virion surface. We compa red the transmembrane topology of newly synthesized LHBs in the endopl asmic reticulum (ER) membrane with its topology in the envelope of sec reted virions. Protease sensitivity and the absence of glycosylation s uggest that the entire preS domain of newly synthesized LHBs remains a t the cytosolic side of ER vesicles. However, virions secreted from tr ansfected cell cultures or isolated from the blood of persistent virus carriers expose antibody binding sites and proteolytic cleavage sites of the preS domain at their surface in approximately half of the LHBs molecules. Thus, preS domains appear to be transported across the vir al lipid barrier by a novel post-translational translocation mechanism to fulfil a dual function in virion assembly and attachment to the ho st cell.