HepG2 cell binding activities of different hepatitis B virus isolates: inhibitory effect of anti-HBs and anti-preS1(21-47).
The antigenic relationships among different hepatitis B virus (HBV) isolates were investigated by using monoclonal antibodies (MAbs) specific for HBs, preS2 (pHSA binding site), and preS1 (hepatocyte receptor-binding site) epitopes in a double immunoradiometric assay. In order to define possible functional differences resulting from structural and antigenic differences in the HBV env protein, the HBV isolates were compared in an in vitro cell-binding assay based on the attachment of 125I-labeled HBV to human hepatoma HepG2 cells. We provided evidence for a variability of the expression of preS1 and preS2 specificities in the peplomer (glyco)protein of HBV depending on dly subtype of HBsAg, which could affect the viral infectivity. We showed that the integrity of the HBV envelope structure associated with a large expression of preS1(21-47) epitopes is an essential factor for effective binding to HepG2 cells. Interestingly, the HBs-specific MAbs directed to disulfide-bond-dependent epitopes were found to be the best inhibitors of the preS1-HepG2 cell interaction (greater than 50%, at the final concentration of 0.5 micrograms/ml). The MAb F35.25 directed to the preS1(21-47) sequence corresponding to the hepatocyte receptor recognition site was, however, also found to inhibit binding. Thus, our results demonstrate the abilities of both anti-HBs and anti-preS(21-41) to block the attachment of complete HBV particles to HepG2 cells, suggesting that these antibodies should be virus neutralizing and would be expected to confer protection against reinfection.
INSERM U131, Clamart, France.
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MA
Petit
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S
Dubanchet
F
F
Capel
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P
Voet
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Dauguet
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P
Hauser
D000911:Antibodies, Monoclonal; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D003673:Defective Viruses / Q000276:immunology / Q000502:physiology / Q000648:ultrastructure; D000939:Epitopes / Q000032:analysis; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology* / Q000502:physiology / Q000648:ultrastructure; D006801:Humans; D008113:Liver Neoplasms; D011863:Radioimmunoassay; D011991:Receptors, Virus / Q000276:immunology / Q000502:physiology*; D014759:Viral Envelope Proteins / Q000276:immunology
D000911:Antibodies, Monoclonal; D000939:Epitopes; D006514:Hepatitis B Surface Antigens; D011991:Receptors, Virus; D014759:Viral Envelope Proteins