BOTH PRE-S1 AND S-DOMAIN OF HEPATITIS-B VIRUS ENVELOPE PROTEINS INTERACT WITH THE CORE PARTICLE

The three envelope proteins of the hepatitis B virus (HBV) are encoded by a single open reading frame in the genome containing three separat e in-phase AUG codons. This organization defines three protein domains (pre-S1, pre-S2, S) which form the small (S), middle (M, pre-S2/S), a nd large (L, pre-S1/pre-S2/S) proteins. Mature virions are generated b y the budding of preformed nucleocapsids through endoplasmic reticulum (ER) membranes containing S and L proteins, whereas the M protein is not necessary. This suggests an important function for the pre-S1 doma in. To investigate the protein-protein interactions involved during th e maturation process of the HBV virion, we studied in vitro the bindin g affinity to purified HBV core particles of various synthetic peptide s identical to regions of the envelope proteins. Data previously obtai ned with deletion mutants were confirmed and refined. The 13 C-termina l amino acids of pre-S1 bound efficiently to core particles, whereas o ther pre-S domains did not. Moreover, the amino acid sequence 56-80 in the cytosolic loop of S bound efficiently to the HBV core. This doubl e interaction between the HBV capside and both S and pre-S1 domains ma y be required for virion morphogenesis. (C) 1997 Academic Press.