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
Birnbaum, F. and M. Nassal. (1990) Hepatitis B virus nucleocapsid assembly: primary structure requirements in the core protein. J. Virol. 64, 3319–3330.
Nassal, M. and Schaller, H. (1996) Hepatitis B virus replication—an update. J. Viral Hepat. 3, 217–226.
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.
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.
Bruss, V., and Ganem, D. (1991) The role of envelope proteins in hepatitis B virus assembly. Proc. Natl. Acad. Sci. USA 88, 1059–1063.
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.
Akarca, U. S. and Lok, A. S. F. (1995) Naturally occurring hepatitis B virus core gene mutations. Hepatology 22, 50–60.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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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
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