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. 1984 Apr;115(1):125–134.

Immunopathologic aspects of woodchuck hepatitis.

D Frommel, D Crevat, L Vitvitsky, C Pichoud, O Hantz, M Chevalier, J A Grimaud, J Lindberg, C G Trépo
PMCID: PMC1900361  PMID: 6324594

Abstract

The natural history of infection with woodchuck hepatitis virus (WHV) has been studied in a colony of 38 Marmota monax. Besides serologic assessment for WHV markers, light-microscopic findings of 61 liver biopsies were correlated with the results of immunofluorescence analysis for nucleocapsid (WHcAg) and surface (WHsAg) antigens. Twenty-four chronic WHsAg carriers all featured signs of continuous viral replication. Two major immunomorphologic patterns were observed in their livers: 1) portal hepatitis in which WHcAg accumulated in the cytoplasm and WHsAg was associated with the hepatocyte membrane and 2) periportal hepatitis in which WHcAg shifted toward nuclear localization and WHsAg became mostly intracytoplasmic. Progression from portal to periportal hepatitis, observed in 7 woodchucks, appeared to be induced by a partial recovery of specific immune reactivity to WHV, insufficient, however, to interrupt WHV replication. Deposits of WHsAg and immunoglobulins were present in the kidney and spleen of animals with severe hepatitis.

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  1. Aldershvile J., Dietrichson O., Skinhøj P., Kryger P., Mathiesen L. R., Christoffersen P., Nielsen J. O. Chronic persistent hepatitis: serological classification and meaning of the hepatitis B e system. Hepatology. 1982 Mar-Apr;2(2):243–246. doi: 10.1002/hep.1840020209. [DOI] [PubMed] [Google Scholar]
  2. Brechot C., Hadchouel M., Scotto J., Degos F., Charnay P., Trepo C., Tiollais P. Detection of hepatitis B virus DNA in liver and serum: a direct appraisal of the chronic carrier state. Lancet. 1981 Oct 10;2(8250):765–768. doi: 10.1016/s0140-6736(81)90182-3. [DOI] [PubMed] [Google Scholar]
  3. Cote P. J., Jr, Dapolito G. M., Shih J. W., Gerin J. L. Surface antigenic determinants of mammalian "hepadnaviruses" defined by group- and class-specific monoclonal antibodies. J Virol. 1982 Apr;42(1):135–142. doi: 10.1128/jvi.42.1.135-142.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dejean A., Vitvitski L., Brechot C., Trepo C., Tiollais P., Charnay P. Presence and state of woodchuck hepatitis virus DNA in liver and serum of woodchucks: further analogies with human hepatitis B virus. Virology. 1982 Aug;121(1):195–199. doi: 10.1016/0042-6822(82)90129-5. [DOI] [PubMed] [Google Scholar]
  5. Edgington T. S., Chisari F. V. Immunological aspects of hepatitis B virus infection. Am J Med Sci. 1975 Sep-Oct;270(2):212–227. [PubMed] [Google Scholar]
  6. Ey P. L., Prowse S. J., Jenkin C. R. Isolation of pure IgG1, IgG2a and IgG2b immunoglobulins from mouse serum using protein A-sepharose. Immunochemistry. 1978 Jul;15(7):429–436. doi: 10.1016/0161-5890(78)90070-6. [DOI] [PubMed] [Google Scholar]
  7. Gajl-Peczalska K. J., Fish A. J., Meuwissen H. J., Frommel D., Good R. A. Localization of immunological complexes fixing beta1C (C3) in germinal centers of lymph nodes. J Exp Med. 1969 Dec 1;130(6):1367–1393. doi: 10.1084/jem.130.6.1367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gefter M. L., Margulies D. H., Scharff M. D. A simple method for polyethylene glycol-promoted hybridization of mouse myeloma cells. Somatic Cell Genet. 1977 Mar;3(2):231–236. doi: 10.1007/BF01551818. [DOI] [PubMed] [Google Scholar]
  9. Goudswaard J., van der Donk J. A., Noordzij A., van Dam R. H., Vaerman J. P. Protein A reactivity of various mammalian immunoglobulins. Scand J Immunol. 1978;8(1):21–28. doi: 10.1111/j.1365-3083.1978.tb00492.x. [DOI] [PubMed] [Google Scholar]
  10. Gudat F., Bianchi L., Sonnabend W., Thiel G., Aenishaenslin W., Stalder G. A. Pattern of core and surface expression in liver tissue reflects state of specific immune response in hepatitis B. Lab Invest. 1975 Jan;32(1):1–9. [PubMed] [Google Scholar]
  11. Halpern M. S., England J. M., Deery D. T., Petcu D. J., Mason W. S., Molnar-Kimber K. L. Viral nucleic acid synthesis and antigen accumulation in pancreas and kidney of Pekin ducks infected with duck hepatitis B virus. Proc Natl Acad Sci U S A. 1983 Aug;80(15):4865–4869. doi: 10.1073/pnas.80.15.4865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hantz O., Pichoud C., Vitvitski L., Trepo C. Use of the cross-reactivity with hepatitis B virus antigens and antibodies for the demonstration of a woodchuck hepatitis virus 'e' antigen-antibody system. J Virol Methods. 1983 Jul;7(1):45–55. doi: 10.1016/0166-0934(83)90022-8. [DOI] [PubMed] [Google Scholar]
  13. Heyward W. L., Bender T. R., Lanier A. P., Francis D. P., McMahon B. J., Maynard J. E. Serological markers of hepatitis B virus and alpha-fetoprotein levels preceding primary hepatocellular carcinoma in Alaskan Eskimos. Lancet. 1982 Oct 23;2(8304):889–891. doi: 10.1016/s0140-6736(82)90863-7. [DOI] [PubMed] [Google Scholar]
  14. Hoofnagle J. H., Dusheiko G. M., Seeff L. B., Jones E. A., Waggoner J. G., Bales Z. B. Seroconversion from hepatitis B e antigen to antibody in chronic type B hepatitis. Ann Intern Med. 1981 Jun;94(6):744–748. doi: 10.7326/0003-4819-94-6-744. [DOI] [PubMed] [Google Scholar]
  15. Hoofnagle J. H., Michalak T., Nowoslawski A., Gerety R. J., Barker L. F. Immunofluorescence microscopy in experimentally induced, type B hepatitis in the chimpanzee. Gastroenterology. 1978 Feb;74(2 Pt 1):182–187. [PubMed] [Google Scholar]
  16. Kaplan P. M., Greenman R. L., Gerin J. L., Purcell R. H., Robinson W. S. DNA polymerase associated with human hepatitis B antigen. J Virol. 1973 Nov;12(5):995–1005. doi: 10.1128/jvi.12.5.995-1005.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Meyer zum Büschenfelde K. H., Hütteroth T. H., Arnold W., Hopf U. Immunologic liver injury: the role of hepatitis B viral antigens and liver membrane antigens as targets. Prog Liver Dis. 1979;6:407–424. [PubMed] [Google Scholar]
  18. Montaño L., Aranguibel F., Boffill M., Goodall A. H., Janossy G., Thomas H. C. An analysis of the composition of the inflammatory infiltrate in autoimmune and hepatitis B virus-induced chronic liver disease. Hepatology. 1983 May-Jun;3(3):292–296. doi: 10.1002/hep.1840030303. [DOI] [PubMed] [Google Scholar]
  19. Nowoslawski A., Krawczynski K., Nazarewicz T., Slusarczyk J. Immunopathological aspects of hepatitis type B. Am J Med Sci. 1975 Sep-Oct;270(2):229–239. doi: 10.1097/00000441-197509000-00002. [DOI] [PubMed] [Google Scholar]
  20. Popper H., Shih J. W., Gerin J. L., Wong D. C., Hoyer B. H., London W. T., Sly D. L., Purcell R. H. Woodchuck hepatitis and hepatocellular carcinoma: correlation of histologic with virologic observations. Hepatology. 1981 Mar-Apr;1(2):91–98. doi: 10.1002/hep.1840010202. [DOI] [PubMed] [Google Scholar]
  21. Ray M. B., Desmet V. J., Bradburne A. F., Desmyter J., Fevery J., De Groote J. Differential distribution of hepatitis B surface antigen and hepatitis B core antigen in the liver of hepatitis B patients. Gastroenterology. 1976 Sep;71(3):462–469. [PubMed] [Google Scholar]
  22. Ray M. B., Desmet V. J., Bradburne A. F., Desmyter J., Fevery J., De Groote J. Hepatitis B core antigen immune complexes in the liver of hepatitis B patients. Clin Exp Immunol. 1979 Jul;37(1):15–24. [PMC free article] [PubMed] [Google Scholar]
  23. Rogler C. E., Summers J. Novel forms of woodchuck hepatitis virus DNA isolated from chronically infected woodchuck liver nuclei. J Virol. 1982 Dec;44(3):852–863. doi: 10.1128/jvi.44.3.852-863.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Scotto J., Hadchouel M., Hery C., Alvarez F., Yvart J., Tiollais P., Bernard O., Brechot C. Hepatitis B virus DNA in children's liver diseases: detection by blot hybridisation in liver and serum. Gut. 1983 Jul;24(7):618–624. doi: 10.1136/gut.24.7.618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Snyder R. L., Tyler G., Summers J. Chronic hepatitis and hepatocellular carcinoma associated with woodchuck hepatitis virus. Am J Pathol. 1982 Jun;107(3):422–425. [PMC free article] [PubMed] [Google Scholar]
  26. Stannard L. M., Hantz O., Trepo C. Antigenic cross-reactions between woodchuck hepatitis virus and human hepatitis B virus shown by immune electron microscopy. J Gen Virol. 1983 Apr;64(Pt 4):975–980. doi: 10.1099/0022-1317-64-4-975. [DOI] [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. Summers J. Three recently described animal virus models for human hepatitis B virus. Hepatology. 1981 Mar-Apr;1(2):179–183. doi: 10.1002/hep.1840010215. [DOI] [PubMed] [Google Scholar]
  29. Thung S. N., Gerber M. A., Purcell R. H., London W. T., Mihalik K. B., Popper H. Animal model of human disease. Chimpanzee carriers of hepatitis B virus. Chimpanzee hepatitis B carriers. Am J Pathol. 1981 Dec;105(3):328–332. [PMC free article] [PubMed] [Google Scholar]
  30. Trepo C. G., Magnius L. O., Schaefer R. A., Prince A. M. Detection of e antigen and antibody: correlations with hapatitis B surface and hepatitis B core antigens, liver disease, and outcome in hepatitis B infections. Gastroenterology. 1976 Nov;71(5):804–808. [PubMed] [Google Scholar]
  31. Trevisan A., Realdi G., Alberti A., Noventa F. Relationship between membrane-bound immunoglobulin and viral antigens in liver cells from patients with hepatitis B virus infection. Gastroenterology. 1979 Aug;77(2):209–214. [PubMed] [Google Scholar]
  32. Tyler G. V., Summers J. W., Synder R. L. Woodchuck hepatitis virus in natural woodchuck populations. J Wildl Dis. 1981 Apr;17(2):297–301. doi: 10.7589/0090-3558-17.2.297. [DOI] [PubMed] [Google Scholar]
  33. Werner B. G., Murphy B. L., Maynard J. E., Larouzé B. Anti-e in primary hepatic carcinoma. Lancet. 1976 Mar 27;1(7961):696–696. doi: 10.1016/s0140-6736(76)92813-0. [DOI] [PubMed] [Google Scholar]
  34. Werner B. G., Smolec J. M., Snyder R., Summers J. Serological relationship of woodchuck hepatitis virus to human hepatitis B virus. J Virol. 1979 Oct;32(1):314–322. doi: 10.1128/jvi.32.1.314-322.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wong D. C., Shih J. W., Purcell R. H., Gerin J. L., London W. T. Natural and experimental infection of woodchucks with woodchuck hepatitis virus, as measured by new, specific assays for woodchuck surface antigen and antibody. J Clin Microbiol. 1982 Mar;15(3):484–490. doi: 10.1128/jcm.15.3.484-490.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]

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