Variable expression of preS1 antigen in serum during chronic hepatitis B virus infection: An accurate marker for the level of hepatitis B virus replication

Abstract

The expression of the preS1 antigen of hepatitis B virus in sera from chronic HBsAg carriers was studied using a specific monoclonal antibody F35.25 in an original, double-immunoradiometric assay. The antibody F35.25 recognized an epitope located between amino-acid residues 32 and 53 on the preS1 sequence of the large HBsAg protein. This domain could be involved in the recognition of hepatitis B virus by hepatocyte receptors. PreS1 antigen detection by monoclonal antibody F35.25 closely correlated with the presence of complete virions in the serum of HBsAg carriers, as demonstrated by ultracentrifugation-gradient experiments and electron-microscopical examination. Of the 19 HBsAg carriers with chronic liver disease, preS1 antigen was detected in 17 (90%): all of the 11 HBeAg- and hepatitis B virus-DNA--positive cases (group 1) and six of eight anti-HBe--positive cases with low levels of hepatitis B virus replication (group 2). PreS1 antigen/HBsAg ratios parallel to preS1 antigen titers were significantly higher in the HBeAg-positive group (34% and 1:10(6] than in the anti-HBe--positive group (18% and 1:10(2]. In contrast, preS1 antigen was not detected in 18 (90%) of the 20 HBsAg healthy carriers positive for anti-HBe and negative for serum hepatitis B virus-DNA (group 3). Our results show that in chronic HBsAg carriers the serum expression of preS1 antigen correlates well with the level of hepatitis B virus replication (serum hepatitis B virus-DNA and/or liver HBcAg) and that it may be useful in assessing the clinical importance of the chronic viral infection.

Early Detection of Viral Resistance by Determination of Hepatitis B Virus Polymerase Mutations in Patients Treated by Lamivudine for Chronic Hepatitis B

“…A semiquantitative determination of the pre-S1 antigen was allowed by the calculation of the ratio of pre-S1 antigen/HBsAg signals as described in detail elsewhere. 25 Analysis of HBV Genome Sequences. Isolation of viral DNA for sequence analysis was performed with standard procedures.…”

In vivo selection of a hepatitis B virus mutant with abnormal viral protein expression

“…Secretion of envelope and capsid proteins into the culture medium was measured by radioimmunoassay (RIA). For envelope protein detection, rabbit polyclonal anti-HBs IgGs were used on the solid phase and monoclonal antibodies directed against HBs (E39.20), preS2 (F124) or preS1 (E35.25) in the detector phase, as described in detail elsewhere (Petit et al, 1990). HBeAg was determined using a commercial RIA from Abbott Laboratories.…”

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

“…Recent data, however, show that serum expression of preSl antigen, detected by monoclonal antibody F 35.25, correlates well with the level of HBV replication [23]; antibody F 35.25 recognizes a different epitope (amino acid residues 32-53) on the preSl sequence, and this could partially explain the discrepancies. Moreover, con trasting results were reported by Budkowska et al [24] concerning serum expression of preS2 antigen in chronic HBV infection, although these authors used the same monoclonal antibody F I24.…”