Interaction between hepatitis delta virus-encoded proteins and hepatitis B virus envelope protein domains.

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

Molecular interactions between hepatitis B virus and delta virus

“…The cytoplasmic orientation of the CYLs of the S protein, provides a reasonable condition for these sites to interact with pre-mature HDV virions in the cytosol (Figure 1) [22] . The importance of S-HBsAg residues 24 to 28 and 56 to 80 for HDV secretion has been shown in previous studies [23,24] . Also, a C-terminal truncation of HBsAg by 50 amino acids inhibits HDV envelopment and secretion [25] .…”

Molecular and clinical aspects of hepatitis D virus infections

“…The HDV ribonucleoprotein (RNP) is surrounded by a mixture of host cell-derived lipids and HBV surface proteins (HBsAg) [9] . HDV has a small single stranded RNA genome of 1679 nucleotids [10] .…”

“…Due to the high degree of intramolecular base pairing in the HDV genome, the RNA folds to an un-branched, rod like structure [11] . HDV's circular RNA forms a complex with two viralencoded proteins, small (195 amino acids) and large (214 amino acids) HDV-antigens (HDAg-S or p24, and HDAg-L or p27, respectively) [6,9,11] . Delta proteins have identical amino acids except for 19 additional residues at the C-terminus of HDAg-L [9] .…”

“…HDV's circular RNA forms a complex with two viralencoded proteins, small (195 amino acids) and large (214 amino acids) HDV-antigens (HDAg-S or p24, and HDAg-L or p27, respectively) [6,9,11] . Delta proteins have identical amino acids except for 19 additional residues at the C-terminus of HDAg-L [9] . The small delta protein acts as a trans-activator for initiation of genomic RNA replication [12] .…”

“…It also undergoes post translational modifications like methylation, acetylation and phosphorylation to mediate viral mRNA transcription in its modified form [10,13] . HDAg-L is a late protein which inhibits viral RNA replication and transcription of viral proteins, interacts with HBV surface antigens and accelerates the assembly of new virions [6,9,11] . The capacity of binding to HBsAg is not only limited to HDAg-L protein but also occurs with HDAg-S.…”