1887

Abstract

SUMMARY

Hepatitis virus B e antigen subtypes HBeAg/1 and HBeAg/2 can be distinguished by a micro-Ouchterlony immunodiffusion assay and a solid-phase radioimmunoassay using serum IgG-associated HBeAgs and liver- and serum-derived IgG-free HBeAgs. The liver- and serum-derived HBeAg consisted of two different antigenicities, HBeAg/1 and HBeAg/2. Both the liver-derived HBeAg/1 and HBeAg/2 had mol. wt. of 30000 (monomer) and 90000 (trimer) and shared the same isoelectric point of 4.3 to 4.8. Approximately 80% of liver-derived HBeAg (mol. wt. 30000 and 90000) had HBeAg/1 activity and the remaining 20% was HBeAg/2. The serum-derived HBeAg/1 and HBeAg/2 were both associated with IgG to form heterogeneous moieties with apparent mol. wt. of 240000, 400000 and 540000 or were free, with mol. wt. 30000 (monomer) and 90000 (trimer). The serum HBeAg of mol. wt. 90000 was further differentiated into two molecular species, one trimer and the other associated with albumin. Large types of both HBeAg/1 and HBeAg/2 were recovered by isoelectrictric focusing at pH 5.5 to 7.5 (mol. wt. 240000), 5.7 to 8.0 (mol. wt. 400000) and 6.4 to 8.4 (mol. wt. 540000) respectively, while small types of both exhibited a narrower range of isoelectric points similar to liver-derived antigens. In most sera, antigenicity of half of the serum IgG-associated HBeAg was HBeAg/1 and the remaining 50% was HBeAg/2, whereas 80% of the free HBeAg had HBeAg/1 activity and the remaining 20% was HBeAg/2. These results indicate that HBeAg/1 and HBeAg/2, although antigenically distinct, are very similar physicochemically with respect to both mol. wt. and isoelectric point. Dissociation of the ‘large’ HBeAg/1 and HBeAg/2 moieties into three mol. wt. species (160000, 32000 and 16000) was achieved by 6--guanidine-HCl treatment followed by gel filtration through Sepharose 6B. The 160000 species was IgG, having both anti-HBeAg/1 and anti-HBeAg/2 activities. In addition, the lower mol. wt. polypeptides (32000 and 16000) exhibited both HBeAg/1 and HBeAg/2 activities. Therefore, we suggest that the IgG associated with the HBeAg molecule forms a true immune complex rather than a non-specific association between HBeAg and IgG. Furthermore, the 32000 mol. wt. polypeptide split into two species of 16000 mol. wt. when heated at 100 °C for 2 min. On the basis of these results, the 16000 mol. wt. polypeptide may be assumed to be the essential polypeptide bearing HBeAg/1 and HBeAg/2 activities in the liver and serum.

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1983-04-01
2024-04-24
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References

  1. Budkowska A., Kalinowska B., Nowoslawski A. 1979; Identification of two HBeAg subspecificities revealed by chemical treatment and enzymatic digestion of liver-derived HBcAg. Journal of Immunology 123:1415–1416
    [Google Scholar]
  2. Fields H. A., Bradley D. W., Davis C. L., Murphy B. L., Schable C. A., Maynard J. E. 1978; Radioimmunoassay for the detection of hepatitis e antigen (HBeAg) and antibody (anti-HBe). Journal of Immunology 121:930–935
    [Google Scholar]
  3. Frösner G. G., Brodersen M., Papaevangelou G., Sugg U., Hass H., Mushahwar I. K., Ling C. M., Overby L. R., Deinhardt F. 1978; Detection of HBeAg and anti-HBe in acute hepatitis B by a sensitive radioimmunoassay. Journal of Medical Virology 3:67–76
    [Google Scholar]
  4. Mcauliffe V. J., Purcell R. H. 1978; Current status of tests for HBeAg and anti-HBe. In Viral Hepatitis pp 161–172 Edited by Vyas G. N., Cohen S. N., Schmid R. Philadelphia: Franklin Institute Press;
    [Google Scholar]
  5. Magnius L. O., Espmark I. A. 1972; New specificities in Australia antigen positive sera distinct from the Le Bouvier determinants. Journal of Immunology 109:1017–1021
    [Google Scholar]
  6. Maynard J. E., Barret D. H., Murphy B. L., Bradley D. W., Berquist K. R., Bender T. R. 1976; Relation of e antigen to hepatitis B virus infection in an area of hyperendemicity. Journal of Infectious Diseases 133:339–342
    [Google Scholar]
  7. Miller D. J., Williams A. E., Le Bouvier G. L., Dwyer J., Grant J. M., Klatski G. 1978; Hepatitis B in hemodialysis patients: significance of HBeAg. Gastroenterology 74:1201–1213
    [Google Scholar]
  8. Murphy B., Tabor E., McAuliffe A., Williams I., Maynard R., Gerety R., Purcell R. 1978; Third component, HBeAg/3, of hepatitis B e antigen system, identified by three different double-diffusion techniques. Journal of Clinical Microbiology 8:349–350
    [Google Scholar]
  9. Mushahwar I. K., Overby L. R., Frösner G., Deinhardt F., Ling C. M. 1978; Prevalence of hepatitis B e antigen and its antibody as detected by radioimmunoassay. Journal of Medical Virology 2:77–87
    [Google Scholar]
  10. Nordenfelt E., Kjellen L. 1975; Dane particles, DNA polymerase and e-antigen in two distinct categories of hepatitis B antigen carriers. Intervirology 5:225–232
    [Google Scholar]
  11. Ohori H., Onodera S., Ishida N. 1979; Demonstration of hepatitis B e antigen (HBeAg) in association with intact Dane particles. Journal of General Virology 43:423–427
    [Google Scholar]
  12. Ohori H., Yamaki M., Onodera S., Yamada E., Ishida N. 1980; Antigenic conversion from HBcAg to HBeAg by degradation of hepatitis B core particles. Intervirology 13:74–82
    [Google Scholar]
  13. Takahashi K., Imai M., MiyaKawa Y., Iwakiri S., Mayumi M. 1978; Duality of hepatitis B e antigen in serum of persons infected with hepatitis B virus: evidence for the nonidentity of e antigen with immunoglobulins. Proceedings of the National Academy of Sciences, U. S. A 75:1952–1956
    [Google Scholar]
  14. Takahashi K., Akahane Y., Gotanda T., Mishiro T., Imai M., Miyakawa Y., Mayumi M. 1979; Demonstration of hepatitis B e antigen in the core of Dane particles. Journal of Immunology 122:275–279
    [Google Scholar]
  15. Trepo C., Hantz O., Vitvitski L., Chevallier P., Williams A., Lemaire J. M., SepeTtjan M. 1978; Heterogeneity and significance of HBeAg: characterization of a third specificity (e3). In Viral Hepatitis pp 203–209 Edited by Vyas G. N., Cohen S. N., Schmid R. Philadelphia: Franklin Institute Press;
    [Google Scholar]
  16. Trepo C., Vitvitski L., Hantz O., Blanchy B., Pichoud C., Beorchia S., Chevallier P., Sepetjan M. 1980; Nature and significance of HBeAg specificities. In Fifth International Congress of Liver Diseases Proceedings, Virus and the Liver pp 49–57 Edited by Bianchi L., Gerok W., Sickinger K., Stalder G. A. Lancaster: MTP Press;
    [Google Scholar]
  17. Williams A., Le Bouvier G. L. 1976; Heterogeneity and thermolability of ‘eʼ. Bibliotheca haematologica 42:71–75
    [Google Scholar]
  18. Yamada E., Ohori H., Ishida N. 1979; Physicochemical heterogeneity of hepatitis B e antigen detected in asymptomatic carriers and carriers in a hemodialysis unit. Journal of Medical Virology 4:33–42
    [Google Scholar]
  19. Yamada E., Ohori H., Ishida N. 1981; Molecular heterogeneity of hepatitis B virus e antigen in liver and serum. Journal of General Virology 55:75–86
    [Google Scholar]
  20. Yoshizawa H., Itoh H., Simonetti J. P., Takahashi K., Machida A., Miyakawa Y., Mayumi M. 1979; Demonstration of hepatitis B e antigen in hepatitis B core particles obtained from the nucleus of hepatocytes infected with hepatitis B virus. Journal of General Virology 42:513–519
    [Google Scholar]
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