Abstract
An estimated 400 million people are chronically infected with hepatitis B virus (HBV) and many will suffer serious liver disease as a consequence. HBV is an enveloped, partially double-stranded DNA virus, which replicates via reverse transcription of an RNA intermediate. The error rate of the reverse transcriptase generates a heterogeneous population of variants, endowing HBV with the ability to evade immune or antiviral selection pressure. Whereas HBV infection can be diagnosed by serological assays, the introduction of new antiviral agents to treat chronic infection requires monitoring by sensitive DNA amplification assays designed for quantification of HBV DNA in serum and liver tissue.
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Selected References
Alberti A. Can serum HBV-DNA be used as a primary end point to assess efficacy of new treatments for chronic hepatitis B? Hepatology 2003;38:18–20.
Bartenschlager R, Schaller H. Hepadnaviral assembly is initiated by poly merase binding to the encapsidation signal in the viral RNA genome. EMBO J 1992;11:3413–3420.
Beasley R, Lin C, Hwang L, Chien C. Hepatocellular carcinoma and hep titis B virus. Lancet 1981;2:1129–1133.
Birnbaum F, Nassal M. Hepatitis B virus nucleocapsid assembly: primary structure requirements in the core protein. J Virol 1990;64:3319–3330.
Brechot C, Thiers V, Kremsdorf D, Nalpas B, Pol S, Paterlini-Brechot P. Persistent hepatitis B virus infection in subjects without hepatitis B surface antigen: clinically significant or purely “occult”? Hepatology 2001;34:194–203.
Carman WF, Jacyna MR, Hadziyannis S, et al. Mutation preventing formation of hepatitis B e antigen in patients with chronic hepatitis B infection. Lancet 1989;2:588–591.
Carman WF, Zanetti AR, Karayiannis P, et al. Vaccine-induced escape mutant of hepatitis B virus. Lancet 1990;336:325–329.
Chang LJ, Pryciak P, Ganem D, Varmus HE. Biosynthesis of the reverse transcriptase of hepatitis B viruses involves de novo translational initiation not ribosomal frameshifting. Nature 1989;337:364–368.
Crowther R, Kiselev N, Bottcher B, et al. Three-dimensional structure of hepatitis B virus core particles determined by electron cryomi croscopy. Cell 1994;77:943–950.
Das K, Xiong X, Yang H, et al. Molecular modeling and biochemical characterization reveal the mechanism of hepatitis B virus polymerase resistance to lamivudine (3TC) and emtricitabine (FTC). J Virol 2001; 75:4771–4779.
Fattovich G, Brollo L, Giustina G, et al. Natural history and prognostic factors for chronic hepatitis type B. Gut 1991;32:294–298.
Ganem D, Schneider R. Hepadnaviridae: The Viruses and Their Replication. In: Knipe DM, Howley PM, eds. Fields Virology, vol. 2, Philadelphia: Lippincott-Raven, 2001; pp. 2923–2970.
Gauthier J, Bourne EJ, Lutz MW, et al. Quantitation of hepatitis B viremia and emergence of YMDD variants in patients with chronic hepatitis B treated with lamivudine. J Infect Dis 1999; 180:1757–1762.
Goodman Z. Histopathology of hepatitis B virus infection. In: Lai CLS, ed. Human Virus Guides, vol. 1, London: International Medical Press, 2002:131–143.
Guidotti LG, Rochford R, Chung J, Shapiro M, Purcell R, Chisari FV. Viral clearance without destruction of infected cells during acute HBV infection. Science 1999;284:825–829.
Gunther S, Fischer L, Pult I, Sterneck M, Will H. Naturally occurring variants of hepatitis B virus. Adv Virus Res 1999;52:25–137.
Hadziyannis SJ, Lieberman HM, Karvountzis GG, Shafritz DA. Analysis of liver disease, nuclear HBcAg, viral replication, and hepatitis B virus DNA in liver and serum of HBeAg vs. anti-HBe positive carriers of hepatitis B virus. Hepatology 1983;3:656–662.
Hino O, Ohtake K, Rogler CE. Features of two hepatitis B virus (HBV) DNA integrations suggest mechanisms of HBV integration. J Virol 1989;63:2638–2643.
Jung M, Pape G. Immunology of hepatitis B infection. Lancet Infect Dis 2002;2:43–50.
Kann M, Gerlich W. Hepadnaviridae: structure and molecular virology. In: Zuckerman A, Thomas H, eds. Viral Hepatitis. London: Churchill Livingstone, 1998:77–105.
Koike K, Tsutsumi T, Fujie H, Shintani Y, Kyoji M. Molecular mechanism of viral hepatocarcinogenesis. Oncology 2002;62(Suppl. 1):29–37.
Lok AS, Akarca U, Greene S. Mutations in the pre-core region of hepatitis B virus serve to enhance the stability of the secondary structure of the pre-genome encapsidation signal. Proc Natl Acad Sci USA 1994;91:4077–4081.
Lok AS, Heathcote EJ, Hoofnagle JH. Management of hepatitis B: 2000-summary of a workshop. Gastroenterology 2001;120:1828–1853.
Milich DR, McLachlan A, Stahl S, et al. Comparative immunogenicity of hepatitis B virus core and E antigens. J Immunol 1988;141:3617–3624.
Naoumov NV, Portmann BC, Tedder RS, et al. Detection of hepatitis B virus antigens in liver tissue. Gastroenterology 1990;99:1248–1253.
Newbold JE, Xin H, Tencza M, et al. The covalently closed duplex form of the hepadnavirus genome exists in situ as a heterogeneous population of viral minochromosomes. J Virol 1995;69:3350–3357.
Nowak MA, Bonhoeffer S, Hill AM, Boehme R, Thomas HC, McDade H. Viral dynamics in hepatitis B virus infection. Proc Natl Acad Sci USA 1996;93:4398–4402.
Richman DD. The impact of drug resistance on the effectiveness of chemotherapy for chronic hepatitis B. Hepatology 2000;32:866,867.
Rossner MT. Review: hepatitis B virus X-gene product: a promiscuous transcriptional activator. J Med Virol 1992;36:101–117.
Saldanha J, Gerlich W, Lelie N, Dawson P, Heermann K, Heath A. An international collaborative study to establish a World Health Organization international standard for hepatitis B virus DNA nucleic acid amplification techniques. Vox Sang 2001;80:63–71.
Schaller H, Fischer M. Transcriptional control of hepadnavirus gene expression. CurrTop Microbiol Immunol 1991;168:21–39.
Schlicht HJ, Bartenschlager R, Schaller H. Biosynthesis and enzymatic functions of the hepadnaviral reverse transcriptase. In: McLachlan A, ed. Molecular Biology of the Hepatitis B Viruses. Boca Raton, FL: CRC Press, 1991:171–180.
Seeger C, Mason WS. Hepatitis B virus biology. Microbiol Mol Biol Rev 2000;64:51–68.
Shaul Y. Regulation of hepadnavirus transcription. In: McLachlan A, ed. Molecular Biology of the Hepatitis B Virus. Boca Raton, FL: CRC Press, 1991:193–211.
Stuyver LJ, Locarnini SA, Lok A, et al. Nomenclature for antiviral-resistant human hepatitis B virus mutations in the polymerase region. Hepatology 2001;33:751–757.
Summers J, Mason WS. Replication of the genome of a hepatitis B-like virus by reverse transcription of an RNA intermediate. Cell 1982;29:403–415.
Summers J, Mason WS. Residual integrated viral DNA after hepadnavirus clearance by nucleoside analog therapy. Proc Natl Acad Sci USA 2004;101:638–640.
Summers J, Smith PM, Horwich AL. Hepadnavirus envelope proteins regulate covalently closed circular DNA amplification. J Virol 1990;64:2819–2824.
Summers J, Jilbert AR, Yang W, et al. Hepatocyte turnover during resolution of a transient hepadnaviral infection. Proc Natl Acad Sci USA 2003;100:11,652–11,659.
Tuttleman JS, Pourcel C, Summers J. Formation of the pool of covalently closed circular viral DNA in hepadnavirus-infected cells. Cell 1986;47:451–460.
Wallace WA, Carman WF. Surface variation of HBV: scientific and medical relevance. Viral Hepat Rev 1997;3:5–16.
Wang GH, Seeger C. Novel mechanism for reverse transcription in hepatitis B viruses. J Virol 1993;67:6507–6512.
Werle B, Bowden D, Locarnini S, et al. Persistence of viral cccDNA during the natural history of chronic hepatitis B and slow decline with adefovir dipivoxil therapy. Gastroenterology 2004;126:1750–1758.
Will H, Reiser W, Weimer T, et al. Replication strategy of human hepatitis B virus. J Virol 1987;61:904–911.
Wu TT, Coates L, Aldrich CE, Summers J, Mason WS. In hepatocytes nfected with duck hepatitis B virus, the template for viral RNA synthesis is amplified by an intracellular pathway. Virology 1990;175:255–261.
Wynne SA, Crowther RA, Leslie AG. The crystal structure of the human hepatitis B virus capsid. Mol Cell 1999;3:771–780.
Zoulim F, Saputelli J, Seeger C. Woodchuck hepatitis virus X protein is required for viral infection in vivo. J Virol 1994;68:2026–2030.
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Bowden, S., Locarnini, S. (2006). Molecular Diagnostics in Hepatitis B. In: Runge, M.S., Patterson, C. (eds) Principles of Molecular Medicine. Humana Press. https://doi.org/10.1007/978-1-59259-963-9_53
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DOI: https://doi.org/10.1007/978-1-59259-963-9_53
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