1887

Abstract

Recently, a new hepatitis B virus (HBV) mutant with HBe antigen-negative phenotype has been characterized, in which one TATA box-like motif of the precore/core promoter had degenerated: most frequently by both A → T and G → A mutations at positions 1762 and 1764, respectively. The clinical significance of this mutant is as yet unknown. In our present study, the T A mutant was sought in sera from HBV-infected blood donors and chronic liver disease patients by directly sequencing a PCR-amplified region of HBV DNA. Also, because the A mutation generates a 3AI cleavage site (GTC → GTC), we digested the PCR products with 3AI to see if cleavage would occur at this specific site. Our results mostly corroborated the earlier report but we found a higher-than-predicted frequency of HBe antigen-positive blood donors positive for the mutant (22%). The titres of HBe antigen in these mutant-positive sera were slightly decreased compared to the titres in wild-type HBV infection. In addition, these blood donors had relatively high (though within the normal range) serum alanine aminotransferase (ALT) levels, suggesting that the T A mutation could be used as a sensitive laboratory marker for insidious hepatitis in these otherwise ‘asymptomatic’ carriers. The 3AI assay, which is much more convenient than sequencing, was shown to be useful for the detection of the T A mutant in an extensive number of clinical samples.

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/content/journal/jgv/10.1099/0022-1317-76-12-3159
1995-12-01
2022-05-28
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References

  1. Bertoletti A., Ferrari C., Fiaccadori F., Penna A., Margolskee R., Schlicht H. J., Fowler P., Guilhot S., Chisari F. V. 1991; HLA class I-restricted human cytotoxic T cells recognize endogenously synthesized hepatitis B virus nucleocapsid antigen. Proceedings of the National Academy of Sciences, USA 88:10445–10449
    [Google Scholar]
  2. Brunetto M. R., Stemler M., Schodel F., Will H., Ottobrelli A., Rizzetto M., Verme G., Bonino F. 1989; Identification of HBV variants which cannot produce precore derived HBeAg and may be responsible for severe hepatitis. Italian Journal of Gastroenterology 21:151–154
    [Google Scholar]
  3. Carman W. F., Jacyna M. R., Hadziyannis S., Karayiannis P., McGarvey M. J., Makris A., Thomas H. C. 1989; Mutation preventing formation of hepatitis B e antigen in patients with chronic hepatitis B infection. Lancet ii:588–591
    [Google Scholar]
  4. Junker-Niepmann M., Bartenschlager R., Schaller H. 1990; A short cis-acting sequence is required for hepatitis B virus pregenome encapsidation and sufficient for packaging of foreign RNA. EMBO Journal 9:3389–3396
    [Google Scholar]
  5. Mondelli M., Vergani G. M., Alberti A., Vergani D., Portmann B., Eddleston A. L. W. F., Williams R. 1982; Specificity of lymphocyte-T cytotoxicity to autologous hepatocytes in chronic hepatitis B virus infection - evidence that T-cells are directed against HBV core antigen expressed on hepatocytes. Journal of Immunology 129:2773–2778
    [Google Scholar]
  6. Okamoto H., Tsuda F., Sakugawa H., Sastrosoewignjo R. I., Imai M., Miyakawa Y., Mayumi M. 1988; Typing hepatitis B virus by homology in nucleotide sequence: comparison of surface antigen subtypes. Journal of General Virology 69:2575–2583
    [Google Scholar]
  7. Okamoto H., Yotsumoto S., Akahane Y., Yamanaka T., Miyazaki Y., Sugai Y., Tsuda F., Tanaka T., Miyakawa Y., Mayumi M. 1990; Hepatitis B viruses with precore region defects prevail in persistently infected hosts along with seroconversion to the antibody against e antigen. Journal of Virology 64:1298–1303
    [Google Scholar]
  8. Okamoto H., Tsuda F., Akahane Y., Sugai Y., Yoshiba M., Moriyama K., Tanaka T., Miyakawa Y., Mayumi M. 1994; Hepatitis B virus with mutations in the core promoter for an e antigen-negative phenotype in carriers with antibody to e antigen. Journal of Virology 68:8102–8110
    [Google Scholar]
  9. Wang Y., Chen P., Wu S., Sun A. L., Wang H., Zhu Y. A., Li Z. P. 1990; A new enhancer element, ENII, identified in the X gene of hepatitis B virus. Journal of Virology 64:3977–3981
    [Google Scholar]
  10. Yuh C. H., Chang Y. L., Ting L. P. 1992; Transcriptional regulation of precore and pregenomic RNAs of hepatitis B virus. Journal of Virology 66:4073–1084
    [Google Scholar]
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