Zusammenfassung
Es ist seit langem unbestritten, daß eine chronische Infektion mit dem humanpathogenen Hepatitis-B-Virus (HBV) eine Leberzirrhose und auch ein primäres hepatozelluläres Karzinom verursachen kann. Welche Eigenschaften des Virus für diese Spätfolgen der Infektion verantwortlich sind, liegt aber noch weitgehend im Dunkeln. In dieser kurzen Übersicht sollen die wichtigsten Hypothesen zur Entstehung von Lebertumoren nach HBV-Infektion diskutiert und einige der experimentellen Ansätze, die zur Klärung dieser zentralen Frage beitragen können, vorgestellt werden.
Summary
It is generally accepted that a chronic hepatitis B virus infection can result in liver cirrhosis and primary hepatocellular carcinoma. However, it is still unclear which characteristics of the virus are responsible for cancerogenesis. In this brief review the most important hypotheses of HBV-induced liver cancer are discussed and some of the experimental strategies which could help to clarify this point are presented.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
Literatur
Ando K, Guidotti L, Wirth S, Schreiber R, Schlicht HJ, Huang S, Chisari FV (1993) Mechanisms of class I restricted immunopathology: A transgenic mouse model of fulminant hepatitis. J Exp Med 178:1541–1554.
Beasley RP (1988) Hepatitis B virus. The major etiology of hepatocellular carcinoma. Cancer 61:1942–1956.
Bertoletti A, Ferrari C, Fiaccadori F, Penna A, Margolskee R, Schlicht HJ, Fowler P, Guilhot S, Chisari FV (1991) HLA class I restricted human cytotoxic T cells recognize endogenously synthesized hepatitis B virus nucleocapsid antigen. Proc Natl Acad Sci USA, 88:10445–10449.
Bertoletti A, Chisari FV, Penna A, Guilhot S, Galati L, Fowler P, Vitiello A, Schlicht HJ, Chesnut R, Fiaccadori F, Ferrari C (1993) Definition of a minimal optimal cytotoxic T cell epitope within the hepatitis B virus nucleocapsid protein. J Virol 67:2376–2380.
Blum HE, Zhang ZS, Galun E, Weizsäcker F von, Garner B, Liang TJ, Wands JR (1992) Hepatitis B virus X protein is not central to the viral life cycle in vitro. J Virol 66:1223–1227.
Chen HS, Kaneko S, Girones R, Anderson RW, Hornbuckle WE, Tennant BC, Cote PJ, Gerin JL, Purcell RH, Miller RH (1993) The woodchuck hepatitis virus X gene is important for establishment of virus infection in woodchucks. J Virol 67:1218–1226.
Chisari FV, Filippi P, Buras J, McLachlan A, Popper H, Pinkert CA, Palmiter RD, Brinster RL (1987) Structural and pathological effects of synthesis of hepatitis B virus large envelope polypeptide in transgenic mice. Proc Natl Acad Sci USA 84:6909–6913.
Chisari FV, Klopchin K, Moriyama T, Pasquinelli C, Dunsford HA, Sell S, Pinkert CA, Brinster RL, Palmiter RD (1989) Molecular pathogenesis of hepatocellular carcinoma in hepatitis B virus transgenic mice. Cell 59:1145–1156.
Guidotti LG, Ando K, Hobbs MV, Ishikawa T, Runkel L, Schreiber RD, Chisari FV (1994) Cytotoxic T lymphocytes inhibit hepatitis B virus gene expression by a noncytolytic mechanism in transgenic mice. Proc Natl Acad Sci USA 91:3764–3768.
Kim CM, Koike K, Saito I, Miyamura T, Jay G (1991) HBx gene of hepatitis B virus induces liver cancer in transgenic mice. Nature 351:317–320.
Koike K, Moriya K, Iino S, Yotsuyanagi H, Endo Y, Miyamura T, Kurokawa K (Guilotti 1994) High-level expression of hepatitis B virus HBx gene and hepatocarcinogenesis in transgenic mice. Hepatology 19:810–819.
Missale G, Brems JJ, Takiff H, Pockros PJ, Chisari FV (1993) Human leukocyte antigen class I-independent pathways may contribute to hepatitis B virus-induced liver disease after liver transplantation. Hepatology 18:491–496.
Missale G, Redeker A, Person J, Fowler P, Guilhot S, Schlicht HJ, Ferrari C, Chisari FV (1993) HLA-A31 and Aw68 restricted cytotoxic T cell responses to a single hepatitis B virus nucleocapsid epitope during acute viral hepatitis. J Exp Med 177: 751–762.
Nayersina R, Fowler P, Guilhot S, Cerny A, Schlicht HJ, Vitiello A, Chesnut R, Person J, Chisari FV (1993) HLA A2 resticted cytotoxic T lymphocyte responses to multiple hepatitis B surface antigen epitopes during hepatitis B virus infection. J Immunol 150:4659–4671.
Popper H, Roth L, Purcell RH, Tennant BC, Gerin JL (1987) Hepatocarcinogenicity of the wood-chuck hepatitis virus. Proc Natl Acad Sci USA 84:866–870.
Rossner MT (1992) Review: hepatitis B virus X-gene product: a promiscuous transcriptional activator. J Med Virol 36:101–117.
Summers J (1981) Three recently described animal virus models for human hepatitis B virus. Hepatology 1:179–183.
Theilmann L, Arnold J, Töx U, Datsis K, Otto G, Hofmann W, Köck J, Schlicht HJ (1994) Liver transplantation and de novo hepatitis B infection (letter). Lancet 343:677–678.
Yaginuma K, Shirakata Y, Kobayashi M, Koike K (1987) Hepatitis B virus (HBV) particles are produced in a cell culture system by transient expression of transfected HBV DNA. Proc Natl Acad Sci USA 84:2678–2682.
Zahm P, Hofschneider PH, Koshy R (1988) The HBV X-ORF encodes a transactivator: a potential factor in viral hepatocarcinogenesis. Oncogene 3:169–177.
Zoulim F, Saputelli J, Seeger C (1994) Woodchuck hepatitis virus X protein is required for viral infection in vivo. J Virol 68:2026–2030.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1995 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Schlicht, HJ., Schmitteckert, E., Reifenberg, K. (1995). Hepatokarzinogenese bei Hepadnaviren und im transgenen Mausmodell. In: Beger, H.G., Manns, M.P., Greten, H. (eds) Molekularbiologische Grundlagen der Gastroenterologie. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-79782-8_10
Download citation
DOI: https://doi.org/10.1007/978-3-642-79782-8_10
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-59325-6
Online ISBN: 978-3-642-79782-8
eBook Packages: Springer Book Archive