Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1991 Apr;65(4):1673–1679. doi: 10.1128/jvi.65.4.1673-1679.1991

Woodchuck hepatitis virus is a more efficient oncogenic agent than ground squirrel hepatitis virus in a common host.

C Seeger 1, B Baldwin 1, W E Hornbuckle 1, A E Yeager 1, B C Tennant 1, P Cote 1, L Ferrell 1, D Ganem 1, H E Varmus 1
PMCID: PMC239970  PMID: 2002538

Abstract

Chronic infection with hepatitis B viruses (hepadnaviruses) is a major cause of hepatocellular carcinoma (HCC), but the incubation time varies from 1 to 2 years to several decades in different host species infected with indigenous viruses. To discern the influence of viral and host factors on the kinetics of induction of HCC, we exploited the recent observation that ground squirrel hepatitis virus (GSHV) is infectious in woodchucks (C. Seeger, P. L. Marion, D. Ganem, and H. E. Varmus, J. Virol. 61:3241-3247, 1987) to compare the pathogenic potential of GSHV and woodchuck hepatitis virus (WHV) in chronically infected woodchucks. Chronic GSHV infection in woodchucks produces mild to moderate portal hepatitis, similar to that observed in woodchucks chronically infected with WHV. However, HCC developed in GSHV carriers about 18 months later than in WHV carriers. Thus, although both viruses are oncogenic in woodchucks, GSHV and WHV differ in oncogenic determinants that can affect the kinetics of appearance of HCC in chronically infected animals.

Full text

PDF
1673

Images in this article

1675Image
on p.1675
1676Image
on p.1676
1677Image
on p.1677

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beasley R. P., Hwang L. Y., Lin C. C., Chien C. S. Hepatocellular carcinoma and hepatitis B virus. A prospective study of 22 707 men in Taiwan. Lancet. 1981 Nov 21;2(8256):1129–1133. doi: 10.1016/s0140-6736(81)90585-7. [DOI] [PubMed] [Google Scholar]
  2. Brechot C., Pourcel C., Louise A., Rain B., Tiollais P. Presence of integrated hepatitis B virus DNA sequences in cellular DNA of human hepatocellular carcinoma. Nature. 1980 Jul 31;286(5772):533–535. doi: 10.1038/286533a0. [DOI] [PubMed] [Google Scholar]
  3. Chakraborty P. R., Ruiz-Opazo N., Shouval D., Shafritz D. A. Identification of integrated hepatitis B virus DNA and expression of viral RNA in an HBsAg-producing human hepatocellular carcinoma cell line. Nature. 1980 Jul 31;286(5772):531–533. doi: 10.1038/286531a0. [DOI] [PubMed] [Google Scholar]
  4. Chisari F. V., Klopchin K., Moriyama T., Pasquinelli C., Dunsford H. A., Sell S., Pinkert C. A., Brinster R. L., Palmiter R. D. Molecular pathogenesis of hepatocellular carcinoma in hepatitis B virus transgenic mice. Cell. 1989 Dec 22;59(6):1145–1156. doi: 10.1016/0092-8674(89)90770-8. [DOI] [PubMed] [Google Scholar]
  5. Colgrove R., Simon G., Ganem D. Transcriptional activation of homologous and heterologous genes by the hepatitis B virus X gene product in cells permissive for viral replication. J Virol. 1989 Sep;63(9):4019–4026. doi: 10.1128/jvi.63.9.4019-4026.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cote P. J., Engle R. E., Langer C. A., Ponzetto A., Gerin J. L. Antigenic analysis of woodchuck hepatitis virus surface antigen with site-specific radioimmunoassays. J Virol. 1984 Mar;49(3):701–708. doi: 10.1128/jvi.49.3.701-708.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cote P. J., Shapiro M., Engle R. E., Popper H., Purcell R. H., Gerin J. L. Protection of chimpanzees from type B hepatitis by immunization with woodchuck hepatitis virus surface antigen. J Virol. 1986 Dec;60(3):895–901. doi: 10.1128/jvi.60.3.895-901.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Edman J. C., Gray P., Valenzuela P., Rall L. B., Rutter W. J. Integration of hepatitis B virus sequences and their expression in a human hepatoma cell. Nature. 1980 Jul 31;286(5772):535–538. doi: 10.1038/286535a0. [DOI] [PubMed] [Google Scholar]
  9. Farber E. Cellular biochemistry of the stepwise development of cancer with chemicals: G. H. A. Clowes memorial lecture. Cancer Res. 1984 Dec;44(12 Pt 1):5463–5474. [PubMed] [Google Scholar]
  10. Farber E. Pre-cancerous steps in carcinogenesis. Their physiological adaptive nature. Biochim Biophys Acta. 1984;738(4):171–180. doi: 10.1016/0304-419x(83)90002-1. [DOI] [PubMed] [Google Scholar]
  11. Ganem D., Varmus H. E. The molecular biology of the hepatitis B viruses. Annu Rev Biochem. 1987;56:651–693. doi: 10.1146/annurev.bi.56.070187.003251. [DOI] [PubMed] [Google Scholar]
  12. Hino O., Ohtake K., Rogler C. E. Features of two hepatitis B virus (HBV) DNA integrations suggest mechanisms of HBV integration. J Virol. 1989 Jun;63(6):2638–2643. doi: 10.1128/jvi.63.6.2638-2643.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hsu T., Möröy T., Etiemble J., Louise A., Trépo C., Tiollais P., Buendia M. A. Activation of c-myc by woodchuck hepatitis virus insertion in hepatocellular carcinoma. Cell. 1988 Nov 18;55(4):627–635. doi: 10.1016/0092-8674(88)90221-8. [DOI] [PubMed] [Google Scholar]
  14. Kodama K., Ogasawara N., Yoshikawa H., Murakami S. Nucleotide sequence of a cloned woodchuck hepatitis virus genome: evolutional relationship between hepadnaviruses. J Virol. 1985 Dec;56(3):978–986. doi: 10.1128/jvi.56.3.978-986.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Korba B. E., Cote P. J., Wells F. V., Baldwin B., Popper H., Purcell R. H., Tennant B. C., Gerin J. L. Natural history of woodchuck hepatitis virus infections during the course of experimental viral infection: molecular virologic features of the liver and lymphoid tissues. J Virol. 1989 Mar;63(3):1360–1370. doi: 10.1128/jvi.63.3.1360-1370.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Marion P. L., Oshiro L. S., Regnery D. C., Scullard G. H., Robinson W. S. A virus in Beechey ground squirrels that is related to hepatitis B virus of humans. Proc Natl Acad Sci U S A. 1980 May;77(5):2941–2945. doi: 10.1073/pnas.77.5.2941. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Marion P. L., Van Davelaar M. J., Knight S. S., Salazar F. H., Garcia G., Popper H., Robinson W. S. Hepatocellular carcinoma in ground squirrels persistently infected with ground squirrel hepatitis virus. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4543–4546. doi: 10.1073/pnas.83.12.4543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Mason W. S., Aldrich C., Summers J., Taylor J. M. Asymmetric replication of duck hepatitis B virus DNA in liver cells: Free minus-strand DNA. Proc Natl Acad Sci U S A. 1982 Jul;79(13):3997–4001. doi: 10.1073/pnas.79.13.3997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Möröy T., Marchio A., Etiemble J., Trépo C., Tiollais P., Buendia M. A. Rearrangement and enhanced expression of c-myc in hepatocellular carcinoma of hepatitis virus infected woodchucks. Nature. 1986 Nov 20;324(6094):276–279. doi: 10.1038/324276a0. [DOI] [PubMed] [Google Scholar]
  20. Ochiya T., Fujiyama A., Fukushige S., Hatada I., Matsubara K. Molecular cloning of an oncogene from a human hepatocellular carcinoma. Proc Natl Acad Sci U S A. 1986 Jul;83(14):4993–4997. doi: 10.1073/pnas.83.14.4993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ponzetto A., Cote P. J., Ford E. C., Purcell R. H., Gerin J. L. Core antigen and antibody in woodchucks after infection with woodchuck hepatitis virus. J Virol. 1984 Oct;52(1):70–76. doi: 10.1128/jvi.52.1.70-76.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Popper H., Roth L., Purcell R. H., Tennant B. C., Gerin J. L. Hepatocarcinogenicity of the woodchuck hepatitis virus. Proc Natl Acad Sci U S A. 1987 Feb;84(3):866–870. doi: 10.1073/pnas.84.3.866. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Seeger C., Ganem D., Varmus H. E. Nucleotide sequence of an infectious molecularly cloned genome of ground squirrel hepatitis virus. J Virol. 1984 Aug;51(2):367–375. doi: 10.1128/jvi.51.2.367-375.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Seeger C., Ganem D., Varmus H. E. The cloned genome of ground squirrel hepatitis virus is infectious in the animal. Proc Natl Acad Sci U S A. 1984 Sep;81(18):5849–5852. doi: 10.1073/pnas.81.18.5849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Seeger C., Marion P. L., Ganem D., Varmus H. E. In vitro recombinants of ground squirrel and woodchuck hepatitis viral DNAs produce infectious virus in squirrels. J Virol. 1987 Oct;61(10):3241–3247. doi: 10.1128/jvi.61.10.3241-3247.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Spandau D. F., Lee C. H. trans-activation of viral enhancers by the hepatitis B virus X protein. J Virol. 1988 Feb;62(2):427–434. doi: 10.1128/jvi.62.2.427-434.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Summers J., Smolec J. M., Snyder R. A virus similar to human hepatitis B virus associated with hepatitis and hepatoma in woodchucks. Proc Natl Acad Sci U S A. 1978 Sep;75(9):4533–4537. doi: 10.1073/pnas.75.9.4533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Szmuness W. Hepatocellular carcinoma and the hepatitis B virus: evidence for a causal association. Prog Med Virol. 1978;24:40–69. [PubMed] [Google Scholar]
  29. Weiser B., Ganem D., Seeger C., Varmus H. E. Closed circular viral DNA and asymmetrical heterogeneous forms in livers from animals infected with ground squirrel hepatitis virus. J Virol. 1983 Oct;48(1):1–9. doi: 10.1128/jvi.48.1.1-9.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES