Pre‐S1 and pre‐S2 gene‐encoded proteins in liver and serum in chronic hepatitis delta infection

Abstract

Frozen cryostat sections and sera from 30 patients with chronic delta infection were examined for pre-S1 and pre-S2 gene-encoded proteins, and the results were compared to markers in liver and serum HBV and HDV replication. Pre-S1 and pre-S2 were detected by indirect immunofluorescence (IF) in the liver in all 26 patients with histochemically demonstrable HBsAg. Pre-S peptides were found by double IF to have a predominantly cytoplasmic expression and to be located in the same hepatocytes expressing HBsAg. Liver cells expressing hepatitis delta antigen (HDAg) were frequently negative or very weakly positive for HBsAg and pre-S peptides, but occasional HDAg positive hepatocytes were also strongly positive for HBsAg and for pre-S peptides, particularly pre-S2. Circulating pre-S1 was detected in 24 patients (80%) and pre-S2 in 27 (90%). Detection of pre-S peptides in liver and serum was independent of HBV and HDV replication and of the HBV-DNA integration state. There was no correlation between the amount of circulating pre-S peptides and serum HBV-DNA and HDV-RNA. These results indicate that in chronic HDV infection, formation and secretion of pre-S peptides and of HBsAg occur independently of HBV and HDV replication and secretion. They further indicate that in the acquisition by replicating HDV of an HBV-derived envelope in the liver, both HBsAg and pre-S peptides are concomitantly available but circulating HDV-RNA is not invariably associated with the presence of these peptides in serum.

Cell Culture Systems for Studying Hepatitis B and Hepatitis D Virus Infections

“…While L-HBsAg is not required for HDV assembly and release, it is essential for HDV infectivity [37]. However, the presence of pre-S proteins and HBsAg in the liver and serum does not indicate the replication of HBV, HDV, and secretion [22,46], suggesting that HDV replication occurs independently from HBV. The HDV genome does not encode its own polymerase but utilizes the host RNA polymerase II the viral replication, while HBV has its own viral polymerase that can be targeted by specific inhibitors [47].…”

Occurrence of Hepatitis Delta Virus Infection in Hepatitis B Virus-Infected Patients with Different Serum Patterns of PreS Gene-Encoded Proteins

“…Transfection experiments have shown that HDV can replicate within infected cells without helper virus [5,6,27], and that the helper function of HBV is to provide the envelope proteins in HDV virion assembly [28]. Recent data indicate that in the acquisition by repli- 12 Napoli/Fiorc/Fcra/Modugno/Giannelli/ Manghisi/Schiraldi eating HDV of an HBV-derived envelope in the liver, both HBsAg and preS proteins are concomitantly avail able [8]. Further investigations are necessary to establish whether the preSl and preS2 proteins are involved in the spread of HDV.…”

“…By using Western blot technique, Theilmann et al [7] have found that only 12% of HBsAg-positive anti-HD-positive patients had preSl proteins in the serum; more recently, preSl and preS2 peptides, detected by means of an immunoenzymatic reaction, have been found in 80 and 90% of patients with chronic HDV infec tion, respectively [8],…”