INTRACELLULAR RETENTION OF HEPATITIS-B VIRUS SURFACE PROTEIN MUTANTS DEVOID OF AMINO-TERMINAL PRE-S1 SEQUENCES

To study the mechanism of L protein-mediated, intracellular (pre-Golgi ) retention of hepatitis B virus (HBV) surface proteins, a collection of HBV preS-S open reading frame variants bearing wild-type or modifie d preS extensions was expressed in human cells. When the secretion phe notype of the corresponding proteins was analysed, all surface protein s with rearranged preS domains were found to be at least partially ret ained. This held true, in particular, for two variant proteins lacking preS1 amino acids 1 to 19 (ayw), the preS1 myristylated N terminus an d a putative retention domain, and for another variant lacking the ent ire preS 1 domain plus the N-terminal portion (amino acids 1 to 12) of the preS2 domain. All the retained variants underwent intracellular d imerization/oligomerization via disulphide bonds to a degree comparabl e to that observed in well exported natural proteins. Our results show that retention can take place in the absence oft N-terminal sequences and does not imply inhibition of covalent oligomerization.