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A cis/trans Genetic Test for Pleiotropic Phenotypes Associated with a Frequent Naturally Occurring Mutation at Amino Acid 97 of HBV Core Protein

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Hepatitis B and D Protocols

Part of the book series: Methods in Molecular Medicine ((MIMM,volume 95))

Abstract

Hepatitis B virus (HBV) is a major human infectious pathogen. Worldwide, there are more than 350 million chronic carriers of HBV. Sequence divergence within the HBV genome is observed during long-term infection of HBV in patients as a result of the low fidelity of HBV reverse transcriptase. The important roles played by naturally occurring HBV variants have been implicated in the development of chronic hepatitis B. However, functional characterization of HBV variants remains difficult because of the lack of a priori knowledge to predict the possible abnormality of variants and to choose the relevant functional assay accordingly. This issue is further complicated by the possibility that a mutant phenotype could arise from either the trans defect of a mutant protein or the cis defect of a mutated genome.

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References

  1. Birnbaum, F. and M. Nassal. (1990) Hepatitis B virus nucleocapsid assembly: primary structure requirements in the core protein. J. Virol. 64, 3319–3330.

    PubMed  CAS  Google Scholar 

  2. Nassal, M. and Schaller, H. (1996) Hepatitis B virus replication—an update. J. Viral Hepat. 3, 217–226.

    Article  PubMed  CAS  Google Scholar 

  3. Haton, T, Zhou, S., and Standring, D. N. (1992) RNA-and DNA-binding activities in hepatitis B virus capsid protein: a model for their roles in viral replication. J. Virol. 66, 5232–5241.

    Google Scholar 

  4. Tuttleman, J., Pourcel, C, and Summers, J. (1986) Formation of the pool of covalently closed viral DNA in hepadnavirus-infected cells. Cell 47, 451–460.

    Article  PubMed  CAS  Google Scholar 

  5. Bruss, V., and Ganem, D. (1991) The role of envelope proteins in hepatitis B virus assembly. Proc. Natl. Acad. Sci. USA 88, 1059–1063.

    Article  PubMed  CAS  Google Scholar 

  6. Ou, J.-H. and Rutter, W. J. (1987) Regulation of secretion of the hepatitis B virus major surface antigen by the pre-S1 protein. J. Virol. 61, 782–786.

    PubMed  CAS  Google Scholar 

  7. Akarca, U. S. and Lok, A. S. F. (1995) Naturally occurring hepatitis B virus core gene mutations. Hepatology 22, 50–60.

    PubMed  CAS  Google Scholar 

  8. Bozkaya, H, Ayola, B., and Lok, A. S.F (1996) High rate of mutations in the hepatitis B core gene during the immune clearance phase of chronic hepatitis B virus infection. Hepatology 24, 32–37.

    Article  PubMed  CAS  Google Scholar 

  9. Chuang, W. L., Omata, M., Ehata, T, Yokosuka, O., Ito, Y., and Ohto, M. (1993) Concentrating missense mutations in core gene of hepatitis B virus. Dig. Dis. Sci. 38, 594–600.

    Article  PubMed  CAS  Google Scholar 

  10. Chuang, W. L., Omata, M., Ehata, T, et al. (1993) Precore mutations and core clustering mutations in chronic hepatitis B virus infection. Gastroenterology 104, 263–271.

    PubMed  CAS  Google Scholar 

  11. Ehata, T., Omata, M., Yokosuka, O., Hosoda, K., and Ohto, M. (1992) Variations in codons 84–101 in the core nucleotide sequence correlate with hepatocellular injury in chronic hepatitis B virus infection. J. Clin. Invest. 89, 332–338.

    Article  PubMed  CAS  Google Scholar 

  12. Ehata, T., Omata, M., Chuang, W. L., et al. (1993) Mutations in core nucleotide sequence of hepatitis B virus correlate with fulminant and severe hepatitis. J. Clin. Invest. 91, 1206–1213.

    Article  PubMed  CAS  Google Scholar 

  13. Gotoh, K., Mima, S., Uchida, T., Shikata, T., Yoshizawa, K., Irie, M., and Mizui, M. (1995) Nucleotide sequence of hepatitis B virus isolated from subjects without serum anti-hepatitis B core antibody. J. Med. Virol. 46, 201–206.

    Article  PubMed  CAS  Google Scholar 

  14. Gray, A. H., Fang, J. W. S., Davis, G. L., et al. (1997) Variations of hepatitis B virus core gene sequence in Western patients with chronic hepatitis B virus infection. J. Viral Hepatitis 4, 371–378.

    Article  CAS  Google Scholar 

  15. Gunther, S., Baginski, S., Kissel, H., et al. (1996) Accumulation and persistence of hepatitis B virus core gene deletion mutants in renal transplant patients are associated with end-stage liver disease. Hepatology 24, 751–758.

    Article  PubMed  CAS  Google Scholar 

  16. Hosono, S., Tai, P. C., Wang, W., et al. (1995) Core antigen mutations of human hepatitis B virus in hepatomas accumulate in MHC class II-restricted T cell epitopes. Virology 212, 151–162.

    Article  PubMed  CAS  Google Scholar 

  17. Hur, G. M., Lee, Y. I., Sun, D. J., Lee, J. H., and Lee, Y. I. (1996) Gradual accumulation of mutations in precore/core region of HBV in patients with chronic active hepatitis: implication of clustering changes in a small region of the HBV core region. J. Med. Virol. 48, 38–46.

    Article  PubMed  CAS  Google Scholar 

  18. Karasawa, T., Shirasawa, T., Okawa, Y., et al. (1997) Association between frequency of amino acid changes in core region of hepatitis B virus (HBV) and the presence of precore mutation in Japanese HBV carriers. J. Gastroenterol. 32, 611–622.

    Article  PubMed  CAS  Google Scholar 

  19. McMillan, J.S., Bowden, D. S., Angus, P. W., McCaughan, G.W., and Locarnini, S. A. (1996) Mutations in the hepatitis B virus precore/core and core promoter in patients with severe recurrent disease following liver transplantation. Hepatology 24, 1371–1378.

    Article  PubMed  CAS  Google Scholar 

  20. Miska, S., Gunther, S., Vassilev, M., Meisel, H., Pape, G., and Will, H. (1993) Heterogeneity of hepatitis B virus C-gene sequences: implications for amplification and sequencing. J. Heptol. 18, 53–61.

    Article  CAS  Google Scholar 

  21. Pollicino, T., Campo, S., and Raimondo, G. (1995) PreS and core gene heterogeneity in hepatitis B virus (HBV) genomes isolated from patients with long-lasting HBV chronic infection. Virology 208, 672–677.

    Article  PubMed  CAS  Google Scholar 

  22. Pollicino, T. S., Zanetti, A. R., Cacciola, I., et al. (1997) Pre-S2 defective hepatitis B virus infection in patients with fulminant hepatitis. Hepatology 26, 495–499.

    Article  PubMed  CAS  Google Scholar 

  23. Rodriguez-Frias, F., Buti, M., Jardi, R., et al. (1995) Hepatitis B virus infection: precore mutants and its relation to viral genotypes and core mutations. Hepatology 22, 1641–1647.

    Article  PubMed  CAS  Google Scholar 

  24. Uchida, T., Aye, T. T., Becher, S. O., et al. (1993) Detection of precore/core-mutant hepatitis B virus genome in patients with acute or fulminant hepatitis without serological markers for recent HBV infection. J. Hepatol. 18, 369–372.

    Article  PubMed  CAS  Google Scholar 

  25. Uchida, T., Aye, T. T., Shihata, T., et al. (1994) Evolution of the hepatitis B virus gene during chronic infection in seven patients. J. Med. Virol. 43, 148–154.

    Article  PubMed  CAS  Google Scholar 

  26. Valliammai, T., Thyagarajan, S. P., Zuckerman, A. J., and Harrison, T. J. (1995) Precore and core mutations in HBV from individuals in India with chronic infection. J. Med. Virol. 45, 321–325.

    Article  PubMed  CAS  Google Scholar 

  27. Yuan, T. T., Sahu, G.K., Whitehead, W. E., Greenberg, R., and Shih, C. (1999) The mechanism of an immature secretion phenotype of a highly frequent naturally occurring missense mutation at codon 97 of human hepatitis B virus core antigen. J. Virol. 73, 5731–5740.

    PubMed  CAS  Google Scholar 

  28. Yuan, T. T., Tai, P. C., and Shih, C. (1999) Subtype-independent immature secretion and subtype-dependent replication deficiency of a highly frequent, naturally occurring mutation of human hepatitis B virus core antigen. J. Virol. 73, 10122–10128.

    PubMed  CAS  Google Scholar 

  29. Le Pogam, S. and Shih, C. (2002) Influence of a putative intermolecular interaction between core and the pre-S1 domain of the large envelope protein on hepatitis B virus secretion. J. Virol. 76, 6510–6517.

    Article  PubMed  Google Scholar 

  30. Summers, J. and Mason, W.S. (1982) Replication of the genome of a hepatitis B-like virus by reverse transcription of an RNA intermediate. Cell 29, 403–415.

    Article  PubMed  CAS  Google Scholar 

  31. Le Pogam, S., Yuan, T. T., Sahu, G. K., Chatterjee, S., and Shih, C. (2000) Low-level secretion of human hepatitis B virus virions caused by two independent, naturally occurring mutations (P5T and L60V) in the capsid protein. J. Virol. 74, 9099–9105.

    Article  PubMed  Google Scholar 

  32. Tai, P. C., Suk, F.M., Gerlich, W. H., Neurath, A. R., and Shih C. C. (2002) Hypermodification and immune escape of an internally deleted middle-envelope (M) protein of frequent and predominant hepatitis B virus variants. Virology 292, 44–58.

    Article  PubMed  CAS  Google Scholar 

  33. Yuan, T. T. and Shih, C. (2000) A frequent, naturally occurring mutation (P130T) of human hepatitis B virus core antigen is compensatory for immature secretion phenotype of another frequent variant (I97L). J. Virol. 74, 4929–4932.

    Article  PubMed  CAS  Google Scholar 

  34. Shih, C., Li, L. S., Roychoudhury, S., and Ho, M. H. (1989) In vitro propagation of human hepatitis B virus in a rat hepatoma cell line. Proc. Natl. Acad. Sci. USA 86, 6323–6327.

    Article  PubMed  CAS  Google Scholar 

  35. Roychoudhury, S., Faruqi, A., and Shih, C. (1991) Pregenomic RNA encapsidation analysis of eleven missense and nonsense polymerase mutants of human hepatitis B virus. J. Virol. 65, 3617–3624.

    PubMed  CAS  Google Scholar 

  36. Yuan, T.-T., Lin, M. H., Qiu, S. M., and Shih, C. (1998) Functional characterization of naturally-occurring variants of human hepatitis B virus containing the core internal deletion mutation. J. Virol. 72, 2168–2176.

    PubMed  CAS  Google Scholar 

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© 2004 Humana Press Inc.

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Shih, C., Yuan, TT.T. (2004). A cis/trans Genetic Test for Pleiotropic Phenotypes Associated with a Frequent Naturally Occurring Mutation at Amino Acid 97 of HBV Core Protein. In: Hamatake, R.K., Lau, J.Y.N. (eds) Hepatitis B and D Protocols. Methods in Molecular Medicine, vol 95. Humana Press. https://doi.org/10.1385/1-59259-669-X:247

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  • DOI: https://doi.org/10.1385/1-59259-669-X:247

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-105-9

  • Online ISBN: 978-1-59259-669-0

  • eBook Packages: Springer Protocols

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