The three envelope proteins of the hepatitis B virus (HBV) are encoded by a single open reading frame in the genome containing three separate 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), and large (L, pre-S1 /pre-S2/S) proteins. Mature virions are generated by 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 domain. To investigate the protein-protein interactions involved during the maturation process of the HBV virion, we studied in vitro the binding affinity to purified HBV core particles of various synthetic peptides identical to regions of the envelope proteins. Data previously obtained with deletion mutants were confirmed and refined. The 13 C-terminal amino acids of pre-S1 bound efficiently to core particles, whereas other 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 double interaction between the HBV capside and both S and pre-S1 domains may be required for virion morphogenesis.

No abstract

Hepatitis delta virus (HDV) packaging requires prenylation of the HDV large protein (p27), as well as a direct protein-protein interaction between HDV proteins and hepatitis B virus (HBV) envelope protein domains. To investigate this interaction, we have analysed the binding capacity of baculovirusexpressed delta p24 and p27 proteins to synthetic peptides specific for the HBV envelope. Although a higher degree of binding was observed with p27, both p24 and p27 could bind HBV envelope peptides. One such peptide corresponded to residues 56-80 located in the cytosolic loop of the small HBV envelope protein, and another corresponded to 23 carboxy-terminal residues of the pre-S1 specific to the large HBV envelope protein. This indicates that in addition to p27, p24 may contribute to packaging of HDV through a proteinprotein interaction with HBV envelope domains, and that an interaction between the pre-S1 polypeptide and delta proteins may play a role in infectivity.Hepatitis delta virus (HDV), a satellite of hepatitis B virus (HBV), can cause fulminant hepatitis and liver cirrhosis in chronically infected patients (Rizzetto, 1983). The HDV virion is coated with an outer envelope composed of host cell-derived lipids and the envelope proteins of HBV. It surrounds an inner ribonucleoprotein (RNP) complex comprising a circular RNA genome and two proteins bearing the hepatitis delta antigen (HD Ag) : the small HD Ag (p24, 195 residues) and the large HD Ag (p27, 214 residues) (Wang et al., 1986 ; Weiner et al., 1988). They are encoded by the HDV genome and their sequences are identical except for 19 additional residues at the carboxy terminus of the large protein