1887

Abstract

We have investigated the molecular basis for the selective advantage of a hepatitis B virus (HBV) mutant. We have determined the complete nucleotide sequences of the major HBV forms identified at the beginning (B1-83) and end (B1-89) of a 6 year follow-up of a chronically infected patient. The B1-89 sequence showed marked nucleotide rearrangements (a nucleotide divergence of 11.3% compared with the adw2 subtype), but sequence comparison showed that both viral molecules were of common origin (62/138 mutations were found on both molecules, compared to adw2). transfection of Huh7 cells showed important modifications in B1-89 viral protein expression. We observed a decrease in B1–89 envelope protein expression associated with a modification of the migration pattern of the large envelope protein. For the B1-89 capsid protein, an insertion of 36 nucleotides at the 5′ end of the C gene resulted in increased expression of a core-specific protein of abnormal size (24 kDa versus 22 kDa). Finally, our data also suggest an increase in the -complementation efficiency of the mutated B1-89 polymerase protein. Thus, we were able to demonstrate distinct intrinsic properties of HBV DNA molecules isolated from a chronic carrier with virus multiplication at different times during infection. Modifications of viral protein expression in the mutated form illustrate strategies used by the virus to prevent clearance and to contribute to viral persistence.

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1996-05-01
2021-10-24
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References

  1. Bartenschlager R., Schaller H. 1992; Hepadnaviral assembly is initiated by polymerase binding to the encapsidation signal in the viral RNA genome. EMBO Journal 9:3413–3420
    [Google Scholar]
  2. Brunetto M. R., Giarin M. M., Oliveri F., Chiaberge E., Baldi M., Alfarano A., Serra A., Saracco G., Verme G., Will H., Bonino F. 1990; Wild-type and e antigen-minus hepatitis B viruses and course of chronic hepatitis. Proceedings of the National Academy of Sciences, USA 88:4186–4190
    [Google Scholar]
  3. Carman W. F., Hadziyannis S., McGarvey M. J., Jacyna M. R., Karayiannis P., Makris A., Thomas H. C. 1989; Mutation preventing formation of hepatitis B e antigen in patients with chronic hepatitis B infection. Lancet ii:588–590
    [Google Scholar]
  4. Carman W. F., Zanetti A. R., Karayiannis P., Waters J., Manzillo G., Tanzi E., Zuckerman A. J., Thomas H. C. 1990; Vaccine-induced escape mutant of hepatitis B virus. Lancet 336:325–329
    [Google Scholar]
  5. Carman W. F., Thomas H. C., Zuckerman A. J., Harrisson T. 1994; Molecular variants. In Viral Hepatitis Scientific Basis and Clinical Management pp 115–136 Edited by Zuckerman A. J., Thomas H. C. London: Churchill Livingstone;
    [Google Scholar]
  6. Chang C., Jeng K.-S., Hu C.-P., Lo S., Su T.-S., Ting L.-P., Chou C.-K., Han S.-H., Pfaff E., Salfeld J., Schaller H. 1987; Production of hepatitis B virus in vitro by transient expression of cloned HBV DNA in hepatoma cell line. EMBO Journal 6:675–680
    [Google Scholar]
  7. Fernholz D., Galle P. R., Stemler M., Brunetto M., Bonino F., Will H. 1993; Infectious hepatitis-B virus variant defective in pre-S2 protein expression in a chronic carrier. Virology 194:137–148
    [Google Scholar]
  8. Ferrari C., Penna A., Bertoletti A., Valli A., Fiaccadori F. 1994; Immunopathogenetic aspects of hepatitis B virus infection. In Primary Liver Cancer: Etiological and Progression Factors pp 137–147 Edited by Brechot London C. CRC Press;
    [Google Scholar]
  9. Ganem D., Varmus H. E. 1987; The molecular biology of the hepatitis B viruses. Annual Review of Biochemistry 56:651–693
    [Google Scholar]
  10. Gerken G., Kremsdorf D., Capel F., Petit M.-A., Dauguet C., Manns M. P., Meyer Zum Buschenfelde K. H., Brechot C. 1991; Hepatitis B defective virus with rearrangements in the PreS gene during chronic HBV infection. Virology 183:555–565
    [Google Scholar]
  11. Gerlich W. H., Heerman K. H. 1991; Hepatitis B virus proteins and virus assembly. In Viral Hepatitis and Liver Disease pp 121–134 Edited by Hollinger F. B., Lemon S. M., Margolies H. S. Baltimore: Williams and Wilkins;
    [Google Scholar]
  12. Guilhot S., Fowler P., Portillo G., Margolskee R. F., Ferrari C., Bertoletti A., Chisari F. V. 1992; Hepatitis B virus (HBV)-specific cytotoxic T-cell response in human: production of target cells by stable expression of HBV-encoded proteins in immortalized human B-cell lines. Journal of Virology 66:2670–2678
    [Google Scholar]
  13. Harrison T. J., Hopes E. A., Oon C. J., Zanetti A. R., Zuckerman A. J. 1991; Independent emergence of a vaccine-induced escape mutant of hepatitis B virus. Journal of Hepatology 13:S105–S107
    [Google Scholar]
  14. Hasegawa K., Huang J., Rogers S. A., Blum H. E., Liang T. J. 1994; Enhanced replication of a hepatitis B mutant associated with an epidemic of fulminant hepatitis. Journal of Virology 68:1651–1659
    [Google Scholar]
  15. Heermann K. H., Golgmann U., Schwartz W., Seyffarth T., Baumgarten H., Gerlich W. H. 1984; Large surface proteins of hepatitis B virus containing the pre-S sequence. Journal of Virology 52:396–402
    [Google Scholar]
  16. Herbomel P., Bourachot B., Yaniv M. 1984; Two distinct enhancers with different cell species specificities coexist in the regulatory region of polyoma. Cell 39:653–662
    [Google Scholar]
  17. Hirsch R. C., Lavine J., Chang L., Varmus H., Ganem D. 1990; Polymerase gene products of hepatitis B viruses are required for genomic packaging as well as for reverse transcription. Nature 344:552–555
    [Google Scholar]
  18. Huang J., Liang T. J. 1993; A novel hepatitis B virus (HBV) genetic element with Rev response element-like properties that is essential for expression of HBV gene products. Molecular and Cellular Biology 13:7476–7486
    [Google Scholar]
  19. Kremsdorf D., Brechot C. 1994; Genetic variability of hepatitis B virus: potential clinical implications. In Primary Liver Cancer: Etiological and Progression Factors pp 149–166 Edited by Brechot C. London: CRC Press;
    [Google Scholar]
  20. Melegari M., Bruno S., Wands J. R. 1994; Properties of hepatitis B virus pre-S1 deletion mutants. Virology 199:292–300
    [Google Scholar]
  21. Nakabaya H., Takeda K., Takoshy Y., Sato J. 1982; Growth of human hepatoma cell lines with differentiated functions in chemically defined medium. Cancer Research 42:3858–3863
    [Google Scholar]
  22. Norder H., Hammas B., Lofdahl S., Courouce A. M., Magnius L. O. 1992; Comparison of amino acid sequences of nine different serotypes of hepatitis B surface antigen and genomic classification of the corresponding hepatitis B virus strains. Journal of General Virology 73:1201–1208
    [Google Scholar]
  23. Okamoto H., Imai M., Kametani M., Nakamura T., Mayumi M. 1987; Genomic heterogeneity of hepatitis B virus in a 54-year-old woman who contracted the infection through materno-fetal transmission. Japanese Journal of Experimental Medicine 57:231–236
    [Google Scholar]
  24. Okamoto H., Omi S., Wang Y., Itoh Y., Tsuda F., Tanaka T., Akahane Y., Miyakawa Y., Mayumi M. 1989; The loss of subtypic determinants in alleles, d/y or w/r, on hepatitis B surface antigen. Molecular Immunology 26:197–205
    [Google Scholar]
  25. Ono Y., Onda H., Sasada R., Igarashi K., Sugino Y., Nishioka K. 1983; The complete nucleotide sequences of the cloned hepatitis B virus DNA: subtype adr and adw. Nucleic Acids Research 11:1747–1757
    [Google Scholar]
  26. Orito E., Mizokami M., Ina Y., Moriyama E. N., Kameshima N., Yamamoto M., Gojobori T. 1989; Host-independent evolution and a genetic classification of the hepadnavirus family based on nucleotide sequences. Proceedings of the National Academy of Sciences, USA 86:7059–7062
    [Google Scholar]
  27. Petit M. A., Zoulim F., Capel F., Dubanchet S., Dauget C., Trepo C. 1990; Variable expression of preSl antigen in serum during chronic hepatitis B virus infection: an accurate marker for the level of hepatitis B virus replication. Hepatology 11:809–814
    [Google Scholar]
  28. Rosmorduc O., Petit M.-A., Pol S., Capel F., Bortolotti F., Berthelot P., Brechot C., Kremsdorf D. 1995; In vivo and in vitro expression of defective hepatitis B virus particles generated by spliced hepatitis B virus RNA. Hepatology 22:10–19
    [Google Scholar]
  29. Santantonio T., Jung M. C., Miska S., Pastore G., Pape G. R., Will H. 1991; Prevalence and type of Pre-C HBV mutants in anti-HBe positive carriers with chronic liver disease in a highly endemic area. Virology 183:840–844
    [Google Scholar]
  30. Santantonio T., Jung M. C., Schneider R., Fernholz D., Milella M., Monno L., Pastore G., Pape G. R., Will H. 1992; Hepatitis B virus genomes that cannot synthesize Pre-S2 proteins occur frequently and as dominant virus populations in chronic carriers in Italy. Virology 188:948–952
    [Google Scholar]
  31. Sells M. A., Chen M.-L., Acs G. 1987; Production of hepatitis B virus particles in Hep G2 cells transfected with cloned hepatitis B virus DNA. Proceedings of the National Academy of Sciences, USA 84:1005–1009
    [Google Scholar]
  32. Tran A., Kremsdorf D., Capel F., Housset C., Dauguet C., Petit M. A., Brechot C. 1991; Emergence of and takeover by hepatitis B virus (HBV) with rearrangements in the Pre-S/S and Pre-C/C genes during chronic HBV infection. Journal of Virology 65:3566–3574
    [Google Scholar]
  33. Yamamoto K., Horikita M., Tsuda F., Itoh K., Akahane Y., Yotsumoto S., Okamoto H., Miyakawa Y., Mayumi M. 1994; Naturally occurring escape mutants of hepatitis B virus with various mutations in the S gene in carriers seropositive for antibody to hepatitis B surface antigen. Journal of Virology 68:2671–2676
    [Google Scholar]
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