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. 1993 Feb;67(2):927–932. doi: 10.1128/jvi.67.2.927-932.1993

Allelic subtypic determinants of hepatitis B surface antigen (i and t) that are distinct from d/y or w/r.

H Ohnuma 1, A Machida 1, H Okamoto 1, F Tsuda 1, M Sakamoto 1, T Tanaka 1, Y Miyakawa 1, M Mayumi 1
PMCID: PMC237446  PMID: 7678309

Abstract

A monoclonal antibody (I-18) was raised against an enneapeptide representing amino acids 125 to 133 of the product of the S gene of hepatitis B virus DNA [S(125-133) segment] with a sequence of Thr-Ile-126-Pro-Ala-Gln-Gly-Thr-Ser-Met. Another monoclonal antibody (T-7) was raised against an S(125-133) segment in which Ile-126 was replaced by Thr-126. In a panel of 16 samples of hepatitis B surface antigen (HBsAg) with known S gene sequences, I-18 reacted with 5 with Ile-126. T-7 reacted with 10 HBsAg samples with Thr-126; it did not, however, react with the remaining one of subtype ayw with Thr-126 flanked by Met-125 and Thr-127. The two allelic subtypic determinants, specified by Ile-126 and Thr-126 and distinct from d/y or w/r, were named i and t after isoleucine and threonine, which regulate them. They were expressed in a mutually exclusive fashion in 216 (83%) of 260 HBsAg samples from asymptomatic carriers. They were not detected in 36 (14%) samples; the failure to detect an i or t determinant was particularly common in HBsAg samples of subtype ayw (26 [79%] of 33). A part of the S gene sequence was determined for eight HBsAg samples without a detectable i or t determinant. They had an Ile-126 or Thr-126 residue that was flanked by Thr-127, not the Pro-127 commonly possessed by HBsAg samples displaying an i or t determinant. Expression of the i/t allele, therefore, would require Pro-127. In eight (3%) of the samples, both i and t determinants were detected; the presence of i and t on the selfsame HBsAg particles was verified by sandwiching the particles between I-18 and T-7. A point mutation from thymine to cytosine at nucleotide 377 in the S gene, contributing different second letters to codon 126 (ATT for Ile and ACT for Thr), would have been responsible for the assembly of HBsAg particles with both i and t determinants by means of phenotypic mixing.

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Selected References

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  1. Bancroft W. H., Mundon F. K., Russell P. K. Detection of additional antigenic determinants of hepatitis B antigen. J Immunol. 1972 Oct;109(4):842–848. [PubMed] [Google Scholar]
  2. Couroucé-Pauty A. M., Plançon A., Soulier J. P. Distribution of HBsAg subtypes in the world. Vox Sang. 1983;44(4):197–211. doi: 10.1111/j.1423-0410.1983.tb01885.x. [DOI] [PubMed] [Google Scholar]
  3. Galibert F., Mandart E., Fitoussi F., Tiollais P., Charnay P. Nucleotide sequence of the hepatitis B virus genome (subtype ayw) cloned in E. coli. Nature. 1979 Oct 25;281(5733):646–650. doi: 10.1038/281646a0. [DOI] [PubMed] [Google Scholar]
  4. Guerrero E., Swenson P. D., Hu P. S., Peterson D. L. The antigenic structure of HBsAg: study of the d/y subtype determinant by chemical modification and site directed mutagenesis. Mol Immunol. 1990 May;27(5):435–441. doi: 10.1016/0161-5890(90)90168-y. [DOI] [PubMed] [Google Scholar]
  5. Ishimaru Y., Ishimaru H., Toda G., Baba K., Mayumi M. An epidemic of infantile papular acrodermatitis (Gianotti's disease) in Japan associated with hepatitis-B surface antigen subtype ayw. Lancet. 1976 Apr 3;1(7962):707–709. doi: 10.1016/s0140-6736(76)93087-7. [DOI] [PubMed] [Google Scholar]
  6. Le Bouvier G. L. The heterogeneity of Australia antigen. J Infect Dis. 1971 Jun;123(6):671–675. doi: 10.1093/infdis/123.6.671. [DOI] [PubMed] [Google Scholar]
  7. Luengrojanakul P., Ohnuma H., Tachibana K., Usuda S., Okamoto H., Tanaka T., Tsuda F., Machida A., Mayumi M. Common and subtypic determinants of hepatitis B surface antigen particles: susceptibility to reduction and/or alkylation evaluated with monoclonal antibodies. Jpn J Exp Med. 1990 Oct;60(5):253–261. [PubMed] [Google Scholar]
  8. Mazzur S., Burgert S., Blumberg B. S. Geographical distribution of Australia antigen determinants d, y and w. Nature. 1974 Jan 4;247(5435):38–40. doi: 10.1038/247038a0. [DOI] [PubMed] [Google Scholar]
  9. Mazzur S., Burgert S., Bouvier G. L. Compound d+y+ particles of Australia antigen. J Immunol. 1975 May;114(5):1510–1512. [PubMed] [Google Scholar]
  10. Merrifield R. B. Solid-phase peptide synthesis. Adv Enzymol Relat Areas Mol Biol. 1969;32:221–296. doi: 10.1002/9780470122778.ch6. [DOI] [PubMed] [Google Scholar]
  11. Mishiro S., Imai M., Takahashi K., Machida A., Gotanda T., Miyakawa Y., Mayumi M. A 49,000-dalton polypeptide bearing all antigenic determinants and full immunogenicity of 22-nm hepatitis B surface antigen particles. J Immunol. 1980 Apr;124(4):1589–1593. [PubMed] [Google Scholar]
  12. Moriyama K., Nakajima E., Hohjoh H., Asayama R., Okochi K. Immunoselected hepatitis B virus mutant. Lancet. 1991 Jan 12;337(8733):125–125. doi: 10.1016/0140-6736(91)90793-o. [DOI] [PubMed] [Google Scholar]
  13. Ohnuma H., Takai E., Machida A., Tsuda F., Okamoto H., Tanaka T., Naito M., Munekata E., Miki K., Miyakawa Y. Synthetic oligopeptides bearing a common or subtypic determinant of hepatitis B surface antigen. J Immunol. 1990 Oct 1;145(7):2265–2271. [PubMed] [Google Scholar]
  14. Okamoto H., Imai M., Kametani M., Nakamura T., Mayumi M. Genomic heterogeneity of hepatitis B virus in a 54-year-old woman who contracted the infection through materno-fetal transmission. Jpn J Exp Med. 1987 Aug;57(4):231–236. [PubMed] [Google Scholar]
  15. Okamoto H., Imai M., Shimozaki M., Hoshi Y., Iizuka H., Gotanda T., Tsuda F., Miyakawa Y., Mayumi M. Nucleotide sequence of a cloned hepatitis B virus genome, subtype ayr: comparison with genomes of the other three subtypes. J Gen Virol. 1986 Nov;67(Pt 11):2305–2314. doi: 10.1099/0022-1317-67-11-2305. [DOI] [PubMed] [Google Scholar]
  16. Okamoto H., Imai M., Tsuda F., Tanaka T., Miyakawa Y., Mayumi M. Point mutation in the S gene of hepatitis B virus for a d/y or w/r subtypic change in two blood donors carrying a surface antigen of compound subtype adyr or adwr. J Virol. 1987 Oct;61(10):3030–3034. doi: 10.1128/jvi.61.10.3030-3034.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Okamoto H., Omi S., Wang Y., Itoh Y., Tsuda F., Tanaka T., Akahane Y., Miyakawa Y., Mayumi M. The loss of subtypic determinants in alleles, d/y or w/r, on hepatitis B surface antigen. Mol Immunol. 1989 Feb;26(2):197–205. doi: 10.1016/0161-5890(89)90102-8. [DOI] [PubMed] [Google Scholar]
  18. Okamoto H., Tsuda F., Sakugawa H., Sastrosoewignjo R. I., Imai M., Miyakawa Y., Mayumi M. Typing hepatitis B virus by homology in nucleotide sequence: comparison of surface antigen subtypes. J Gen Virol. 1988 Oct;69(Pt 10):2575–2583. doi: 10.1099/0022-1317-69-10-2575. [DOI] [PubMed] [Google Scholar]
  19. Paul D. A., Purcell R. H., Peterson D. L. Use of monoclonal antibodies to determine if HBsAg of mixed subtype is one particle or two. J Virol Methods. 1986 Apr;13(1):43–53. doi: 10.1016/0166-0934(86)90071-6. [DOI] [PubMed] [Google Scholar]
  20. Peterson D. L., Paul D. A., Lam J., Tribby I. I., Achord D. T. Antigenic structure of hepatitis B surface antigen: identification of the "d" subtype determinant by chemical modification and use of monoclonal antibodies. J Immunol. 1984 Feb;132(2):920–927. [PubMed] [Google Scholar]
  21. Peterson D. L., Roberts I. M., Vyas G. N. Partial amino acid sequence of two major component polypeptides of hepatitis B surface antigen. Proc Natl Acad Sci U S A. 1977 Apr;74(4):1530–1534. doi: 10.1073/pnas.74.4.1530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sastrosoewignjo R. I., Sandjaja B., Okamoto H. Molecular epidemiology of hepatitis B virus in Indonesia. J Gastroenterol Hepatol. 1991 Sep-Oct;6(5):491–498. doi: 10.1111/j.1440-1746.1991.tb00894.x. [DOI] [PubMed] [Google Scholar]
  23. Shiina S., Fujino H., Uta Y., Tagawa K., Unuma T., Yoneyama M., Ohmori T., Suzuki S., Kurita M., Ohashi Y. Relationship of HBsAg subtypes with HBeAg/anti-HBe status and chronic liver disease. Part I: Analysis of 1744 HBsAg carriers. Am J Gastroenterol. 1991 Jul;86(7):866–871. [PubMed] [Google Scholar]
  24. Sukeno N., Shirachi R., Yamaguchi J., Ishida N. Reduction and reoxidation of Australia antigen: loss and reconstitution of particle structure and antigenicity. J Virol. 1972 Jan;9(1):182–183. doi: 10.1128/jvi.9.1.182-183.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Szmuness W., Stevens C. E., Harley E. J., Zang E. A., Oleszko W. R., William D. C., Sadovsky R., Morrison J. M., Kellner A. Hepatitis B vaccine: demonstration of efficacy in a controlled clinical trial in a high-risk population in the United States. N Engl J Med. 1980 Oct 9;303(15):833–841. doi: 10.1056/NEJM198010093031501. [DOI] [PubMed] [Google Scholar]
  26. Tiollais P., Pourcel C., Dejean A. The hepatitis B virus. Nature. 1985 Oct 10;317(6037):489–495. doi: 10.1038/317489a0. [DOI] [PubMed] [Google Scholar]
  27. Usuda S., Tsuda F., Gotanda T., Tachibana K., Nomura M., Okamoto H., Imai M., Nakamura T., Miyakawa Y., Mayumi M. A solid-phase enzyme immunoassay for the common and subtypic determinants of hepatitis B surface antigen with monoclonal antibodies. J Immunol Methods. 1986 Mar 13;87(2):203–210. doi: 10.1016/0022-1759(86)90532-6. [DOI] [PubMed] [Google Scholar]
  28. Vaudin M., Wolstenholme A. J., Tsiquaye K. N., Zuckerman A. J., Harrison T. J. The complete nucleotide sequence of the genome of a hepatitis B virus isolated from a naturally infected chimpanzee. J Gen Virol. 1988 Jun;69(Pt 6):1383–1389. doi: 10.1099/0022-1317-69-6-1383. [DOI] [PubMed] [Google Scholar]
  29. Vyas G. N., Rao K. R., Ibrahim A. B. Australia antigen (hepatitis B antigen): a conformational antigen dependent on disulfide bonds. Science. 1972 Dec 22;178(4067):1300–1301. doi: 10.1126/science.178.4067.1300. [DOI] [PubMed] [Google Scholar]
  30. Yamanaka T., Akahane Y., Suzuki H., Okamoto H., Tsuda F., Miyakawa Y., Mayumi M. Hepatitis B surface antigen particles with all four subtypic determinants: point mutations of hepatitis B virus DNA inducing phenotypic changes or double infection with viruses of different subtypes. Mol Immunol. 1990 May;27(5):443–449. doi: 10.1016/0161-5890(90)90169-z. [DOI] [PubMed] [Google Scholar]
  31. Yamishita Y., Kurashina S., Miyakawa Y., Mayumi M. South-to-north gradient in distribution of the r determinant of hepatitis B surface antigen in Japan. J Infect Dis. 1975 May;131(5):567–569. doi: 10.1093/infdis/131.5.567. [DOI] [PubMed] [Google Scholar]

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