Inhibition of Albumin Binding to Hepatitis B Virions by Monoclonal Antibody to the PreS2 Domain of the Viral Envelope

Abstract

The binding of polyalbumin to hepatitis B virus (HBV)-associated envelope epitopes has been studied by means of a radioimmunoprecipitation technique. HBV particles were purified from the sera of chronic hepatitis B surface antigen (HBsAg) carriers and labelled through the endogenous HBV-DNA polymerase reaction. Human albumin, polymerized through glutaraldehyde cross-linking, was able to precipitate (100 %) labelled HBV at concentrations of 31.2 and 62.5 μg/ml, in contrast to monomeric albumin (HSA). This event was further confirmed by immune electron microscopy. The addition of anti-HSA to the mixture HBV plus polyalbumin gave a 100% precipitation in a wide dilution range (15.6–500 μg/ml). The binding of polyalbumin (31.2 μg/ml) to virions was strongly inhibited (up to 98%) when preincubating with antibody to a glycosylation-dependent preS2 epitope on HBV. The same was accounted (up to 99%) for polyvalent IgG anti-HBs. However, antibodies to the group ‘a’ and subtype ‘d’ determinants, as well as anti-preS 1 region antibodies, inhibited weakly polyalbumin binding to HBV. The binding site of the inhibitor) antibody overlaps probably with neutralizing epitopes. Our findings support the hypothesi: that albumin binding plays an important role in the viral life cycle.

Interaction Between Hepatitis B Surface Proteins and Monomeric Human Serum Albumin

“…Both the LHBs and the MHBs proteins of HBsAg contain the preS2 domain; in immunoblots both proteins bind gHSA. In uiuo, MHBs is probably the only binding site because the preS2 domain of LHBs is masked by the preSl domain (33,34).…”

Quantitation of large, middle and small hepatitis B surface proteins in HBeAg‐positive patients treated with peginterferon alfa‐2a

“…This suggests that the ratio of internal and external preS1 domains in virions or HBsAg filaments is not highly variable, and that external preS1 domains were not masked by antibody or other serum components in the patients of our study. The preS2 domain of MHBs and possibly also of LHBs is masked to a large degree and, thus, undetectable by the ELISA, as has been shown previously . Deepen et al found high levels of free MHBs in HBeAg‐positive carriers only if the HBsAg concentration was >20 000 ng/mL.…”

“…The preS2 domain of MHBs and possibly also of LHBs is masked to a large degree and, thus, undetectable by the ELISA, as has been shown previously. 27 Deepen et al 8 This study has certain limitations. We evaluated HBs levels retrospectively using stored serum samples from a subset of patients enrolled in a randomized controlled trial.…”

Hepati̇t B Vi̇rüs İnfeksi̇yonu Ve Poli̇meri̇ze İnsan Serum Albumi̇ni̇ Arasindaki̇ İli̇şki̇

“…Bunlar S, Pre Sl ve Pre S2 olarak adlandırılır (1,7). Elektro-foretik analizler bu 3 genetik bölge tarafından sentezlenen 3 yüzey antijen proteini (S protein, M protein, L protein) bulunduğunu gös-termiştir (20). Taşıyıcı kişilerin serumlarından pürifiye edilen HBsAg partikülleri, pHSA ile etkileşim açısından incelendiğinde, M proteini ve L proteini yapısında bulunan ve 55 amino asitten oluşan Pre S2 bölgesinin, pHSA'i bağlama özelliğinde olduğu ortaya konmuştur (6,11).…”