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. 1997 Jun;71(6):4804–4808. doi: 10.1128/jvi.71.6.4804-4808.1997

Hepatitis B virus replication is cell cycle independent during liver regeneration in transgenic mice.

L G Guidotti 1, B Matzke 1, F V Chisari 1
PMCID: PMC191703  PMID: 9151875

Abstract

The content of hepatitis B virus (HBV) replicative forms and HBV core protein in the liver of HBV transgenic mice is transiently reduced during massive liver regeneration following partial hepatectomy while the steady-state content of viral RNA is unchanged. This antiviral effect is triggered by interferon and tumor necrosis factor that are induced in the liver following hepatectomy and either prevent the formation or accelerate the degradation of viral nucleocapsids in the cytoplasm of the hepatocyte. Despite massive hepatocellular turnover, this effect is independent of liver cell division, indicating that HBV replicates efficiently in resting and dividing hepatocytes.

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Selected References

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  1. Ando K., Moriyama T., Guidotti L. G., Wirth S., Schreiber R. D., Schlicht H. J., Huang S. N., Chisari F. V. Mechanisms of class I restricted immunopathology. A transgenic mouse model of fulminant hepatitis. J Exp Med. 1993 Nov 1;178(5):1541–1554. doi: 10.1084/jem.178.5.1541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chisari F. V., Ferrari C. Hepatitis B virus immunopathogenesis. Annu Rev Immunol. 1995;13:29–60. doi: 10.1146/annurev.iy.13.040195.000333. [DOI] [PubMed] [Google Scholar]
  3. Fausto N., Laird A. D., Webber E. M. Liver regeneration. 2. Role of growth factors and cytokines in hepatic regeneration. FASEB J. 1995 Dec;9(15):1527–1536. doi: 10.1096/fasebj.9.15.8529831. [DOI] [PubMed] [Google Scholar]
  4. Fourel I., Cullen J. M., Saputelli J., Aldrich C. E., Schaffer P., Averett D. R., Pugh J., Mason W. S. Evidence that hepatocyte turnover is required for rapid clearance of duck hepatitis B virus during antiviral therapy of chronically infected ducks. J Virol. 1994 Dec;68(12):8321–8330. doi: 10.1128/jvi.68.12.8321-8330.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gresser I., Tovey M. G., Bandu M. E., Maury C., Brouty-Boyé D. Role of interferon in the pathogenesis of virus diseases in mice as demonstrated by the use of anti-interferon serum. I. Rapid evolution of encephalomyocarditis virus infection. J Exp Med. 1976 Nov 2;144(5):1305–1315. doi: 10.1084/jem.144.5.1305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Guidotti L. G., Ando K., Hobbs M. V., Ishikawa T., Runkel L., Schreiber R. D., Chisari F. V. Cytotoxic T lymphocytes inhibit hepatitis B virus gene expression by a noncytolytic mechanism in transgenic mice. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3764–3768. doi: 10.1073/pnas.91.9.3764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Guidotti L. G., Borrow P., Hobbs M. V., Matzke B., Gresser I., Oldstone M. B., Chisari F. V. Viral cross talk: intracellular inactivation of the hepatitis B virus during an unrelated viral infection of the liver. Proc Natl Acad Sci U S A. 1996 May 14;93(10):4589–4594. doi: 10.1073/pnas.93.10.4589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Guidotti L. G., Guilhot S., Chisari F. V. Interleukin-2 and alpha/beta interferon down-regulate hepatitis B virus gene expression in vivo by tumor necrosis factor-dependent and -independent pathways. J Virol. 1994 Mar;68(3):1265–1270. doi: 10.1128/jvi.68.3.1265-1270.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Guidotti L. G., Ishikawa T., Hobbs M. V., Matzke B., Schreiber R., Chisari F. V. Intracellular inactivation of the hepatitis B virus by cytotoxic T lymphocytes. Immunity. 1996 Jan;4(1):25–36. doi: 10.1016/s1074-7613(00)80295-2. [DOI] [PubMed] [Google Scholar]
  10. Guidotti L. G., Martinez V., Loh Y. T., Rogler C. E., Chisari F. V. Hepatitis B virus nucleocapsid particles do not cross the hepatocyte nuclear membrane in transgenic mice. J Virol. 1994 Sep;68(9):5469–5475. doi: 10.1128/jvi.68.9.5469-5475.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Guidotti L. G., Matzke B., Schaller H., Chisari F. V. High-level hepatitis B virus replication in transgenic mice. J Virol. 1995 Oct;69(10):6158–6169. doi: 10.1128/jvi.69.10.6158-6169.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Guilhot S., Guidotti L. G., Chisari F. V. Interleukin-2 downregulates hepatitis B virus gene expression in transgenic mice by a posttranscriptional mechanism. J Virol. 1993 Dec;67(12):7444–7449. doi: 10.1128/jvi.67.12.7444-7449.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Huang S. N., Chisari F. V. Strong, sustained hepatocellular proliferation precedes hepatocarcinogenesis in hepatitis B surface antigen transgenic mice. Hepatology. 1995 Mar;21(3):620–626. [PubMed] [Google Scholar]
  14. Jilbert A. R., Wu T. T., England J. M., Hall P. M., Carp N. Z., O'Connell A. P., Mason W. S. Rapid resolution of duck hepatitis B virus infections occurs after massive hepatocellular involvement. J Virol. 1992 Mar;66(3):1377–1388. doi: 10.1128/jvi.66.3.1377-1388.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kajino K., Jilbert A. R., Saputelli J., Aldrich C. E., Cullen J., Mason W. S. Woodchuck hepatitis virus infections: very rapid recovery after a prolonged viremia and infection of virtually every hepatocyte. J Virol. 1994 Sep;68(9):5792–5803. doi: 10.1128/jvi.68.9.5792-5803.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kurki P., Ogata K., Tan E. M. Monoclonal antibodies to proliferating cell nuclear antigen (PCNA)/cyclin as probes for proliferating cells by immunofluorescence microscopy and flow cytometry. J Immunol Methods. 1988 Apr 22;109(1):49–59. doi: 10.1016/0022-1759(88)90441-3. [DOI] [PubMed] [Google Scholar]
  17. Russell W. E., Coffey R. J., Jr, Ouellette A. J., Moses H. L. Type beta transforming growth factor reversibly inhibits the early proliferative response to partial hepatectomy in the rat. Proc Natl Acad Sci U S A. 1988 Jul;85(14):5126–5130. doi: 10.1073/pnas.85.14.5126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Schreiber R. D., Hicks L. J., Celada A., Buchmeier N. A., Gray P. W. Monoclonal antibodies to murine gamma-interferon which differentially modulate macrophage activation and antiviral activity. J Immunol. 1985 Mar;134(3):1609–1618. [PubMed] [Google Scholar]
  19. Sells M. A., Zelent A. Z., Shvartsman M., Acs G. Replicative intermediates of hepatitis B virus in HepG2 cells that produce infectious virions. J Virol. 1988 Aug;62(8):2836–2844. doi: 10.1128/jvi.62.8.2836-2844.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Sheehan K. C., Ruddle N. H., Schreiber R. D. Generation and characterization of hamster monoclonal antibodies that neutralize murine tumor necrosis factors. J Immunol. 1989 Jun 1;142(11):3884–3893. [PubMed] [Google Scholar]
  21. Tsui L. V., Guidotti L. G., Ishikawa T., Chisari F. V. Posttranscriptional clearance of hepatitis B virus RNA by cytotoxic T lymphocyte-activated hepatocytes. Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12398–12402. doi: 10.1073/pnas.92.26.12398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Uchida T., Kronborg I., Peters R. L. Acute viral hepatitis: morphologic and functional correlations in human livers. Hum Pathol. 1984 Mar;15(3):267–277. doi: 10.1016/s0046-8177(84)80190-2. [DOI] [PubMed] [Google Scholar]

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