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. 1989 Apr;63(4):1612–1618. doi: 10.1128/jvi.63.4.1612-1618.1989

Hepatitis delta virus (HDV) and woodchuck hepatitis virus (WHV) nucleic acids in tissues of HDV-infected chronic WHV carrier woodchucks.

F Negro 1, B E Korba 1, B Forzani 1, B M Baroudy 1, T L Brown 1, J L Gerin 1, A Ponzetto 1
PMCID: PMC248403  PMID: 2926865

Abstract

The molecular forms of genomic and antigenomic hepatitis delta virus (HDV) RNA and of woodchuck hepatitis virus (WHV) DNA and WHV RNA were studied in nonneoplastic liver (NL) tissues, hepatocellular carcinoma (HCC) tissues, and several extrahepatic tissues of chronic WHV carrier woodchucks acutely (two animals) and chronically (six animals) superinfected with HDV. HDV was shown to replicate in all NL and HCC tissues but not in any of the extrahepatic tissues analyzed, which included spleen, peripheral blood lymphocytes, kidney, ovary, testis, thymus, lung, and stomach. HDV RNA was present as species with molecular weights consistent with those of monomers, dimers, and trimers of both strand polarities, supporting the rolling circle model proposed for HDV RNA replication. WHV DNA levels in NL, HCC, spleens, and serum were 10- to 100-fold lower than the levels typically observed in chronic WHV carrier woodchucks not infected with HDV. WHV DNA replicative intermediates were rarely observed and only at very low levels, representing less than 10% of the total WHV DNA. By contrast, WHV RNA transcription was not significantly depressed and both primary WHV RNA transcripts, 2.3 and 3.6 kilobases, were observed in NL, HCC, spleens, and in one of the kidney tissues. In addition, a 2.6-kilobase WHV RNA transcript was found in the majority of the NL tissues.

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Selected References

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  1. Baroudy B. M., Smedile A., Korba B. E., Bergmann K. F., Pohl C., Wells F. V., Gerin J. L. Transcription and replication of hepatitis delta virus. Prog Clin Biol Res. 1987;234:89–91. [PubMed] [Google Scholar]
  2. Bonino F., Heermann K. H., Rizzetto M., Gerlich W. H. Hepatitis delta virus: protein composition of delta antigen and its hepatitis B virus-derived envelope. J Virol. 1986 Jun;58(3):945–950. doi: 10.1128/jvi.58.3.945-950.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Branch A. D., Robertson H. D. A replication cycle for viroids and other small infectious RNA's. Science. 1984 Feb 3;223(4635):450–455. doi: 10.1126/science.6197756. [DOI] [PubMed] [Google Scholar]
  4. Chen P. J., Kalpana G., Goldberg J., Mason W., Werner B., Gerin J., Taylor J. Structure and replication of the genome of the hepatitis delta virus. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8774–8778. doi: 10.1073/pnas.83.22.8774. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cohen J. I., Miller R. H., Rosenblum B., Denniston K., Gerin J. L., Purcell R. H. Sequence comparison of woodchuck hepatitis virus replicative forms shows conservation of the genome. Virology. 1988 Jan;162(1):12–20. doi: 10.1016/0042-6822(88)90389-3. [DOI] [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. Denniston K. J., Hoyer B. H., Smedile A., Wells F. V., Nelson J., Gerin J. L. Cloned fragment of the hepatitis delta virus RNA genome: sequence and diagnostic application. Science. 1986 May 16;232(4752):873–875. doi: 10.1126/science.3704630. [DOI] [PubMed] [Google Scholar]
  8. Enders G. H., Ganem D., Varmus H. Mapping the major transcripts of ground squirrel hepatitis virus: the presumptive template for reverse transcriptase is terminally redundant. Cell. 1985 Aug;42(1):297–308. doi: 10.1016/s0092-8674(85)80125-2. [DOI] [PubMed] [Google Scholar]
  9. Galle P. R., Schlicht H. J., Fischer M., Schaller H. Production of infectious duck hepatitis B virus in a human hepatoma cell line. J Virol. 1988 May;62(5):1736–1740. doi: 10.1128/jvi.62.5.1736-1740.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gowans E. J., Baroudy B. M., Negro F., Ponzetto A., Purcell R. H., Gerin J. L. Evidence for replication of hepatitis delta virus RNA in hepatocyte nuclei after in vivo infection. Virology. 1988 Nov;167(1):274–278. doi: 10.1016/0042-6822(88)90078-5. [DOI] [PubMed] [Google Scholar]
  11. Hadziyannis S. J., Sherman M., Lieberman H. M., Shafritz D. A. Liver disease activity and hepatitis B virus replication in chronic delta antigen-positive hepatitis B virus carriers. Hepatology. 1985 Jul-Aug;5(4):544–547. doi: 10.1002/hep.1840050404. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Hirsch R., Colgrove R., Ganem D. Replication of duck hepatitis B virus in two differentiated human hepatoma cell lines after transfection with cloned viral DNA. Virology. 1988 Nov;167(1):136–142. doi: 10.1016/0042-6822(88)90062-1. [DOI] [PubMed] [Google Scholar]
  14. Korba B. E., Gowans E. J., Wells F. V., Tennant B. C., Clarke R., Gerin J. L. Systemic distribution of woodchuck hepatitis virus in the tissues of experimentally infected woodchucks. Virology. 1988 Jul;165(1):172–181. doi: 10.1016/0042-6822(88)90670-8. [DOI] [PubMed] [Google Scholar]
  15. Korba B. E., Wells F., Tennant B. C., Cote P. J., Gerin J. L. Lymphoid cells in the spleens of woodchuck hepatitis virus-infected woodchucks are a site of active viral replication. J Virol. 1987 May;61(5):1318–1324. doi: 10.1128/jvi.61.5.1318-1324.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kos A., Dijkema R., Arnberg A. C., van der Meide P. H., Schellekens H. The hepatitis delta (delta) virus possesses a circular RNA. Nature. 1986 Oct 9;323(6088):558–560. doi: 10.1038/323558a0. [DOI] [PubMed] [Google Scholar]
  17. Krogsgaard K., Kryger P., Aldershvile J., Andersson P., Sørensen T. I., Nielsen J. O. Delta-infection and suppression of hepatitis B virus replication in chronic HBsAg carriers. Hepatology. 1987 Jan-Feb;7(1):42–45. doi: 10.1002/hep.1840070110. [DOI] [PubMed] [Google Scholar]
  18. Kuo M. Y., Goldberg J., Coates L., Mason W., Gerin J., Taylor J. Molecular cloning of hepatitis delta virus RNA from an infected woodchuck liver: sequence, structure, and applications. J Virol. 1988 Jun;62(6):1855–1861. doi: 10.1128/jvi.62.6.1855-1861.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Makino S., Chang M. F., Shieh C. K., Kamahora T., Vannier D. M., Govindarajan S., Lai M. M. Molecular cloning and sequencing of a human hepatitis delta (delta) virus RNA. Nature. 1987 Sep 24;329(6137):343–346. doi: 10.1038/329343a0. [DOI] [PubMed] [Google Scholar]
  20. Möröy T., Etiemble J., Trépo C., Tiollais P., Buendia M. A. Transcription of woodchuck hepatitis virus in the chronically infected liver. EMBO J. 1985 Jun;4(6):1507–1514. doi: 10.1002/j.1460-2075.1985.tb03810.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Negro F., Bergmann K. F., Baroudy B. M., Satterfield W. C., Popper H., Purcell R. H., Gerin J. L. Chronic hepatitis D virus (HDV) infection in hepatitis B virus carrier chimpanzees experimentally superinfected with HDV. J Infect Dis. 1988 Jul;158(1):151–159. doi: 10.1093/infdis/158.1.151. [DOI] [PubMed] [Google Scholar]
  22. Negro F., Berninger M., Chiaberge E., Gugliotta P., Bussolati G., Actis G. C., Rizzetto M., Bonino F. Detection of HBV-DNA by in situ hybridization using a biotin-labeled probe. J Med Virol. 1985 Apr;15(4):373–382. doi: 10.1002/jmv.1890150407. [DOI] [PubMed] [Google Scholar]
  23. Patterson M., Gonzalez-Vitale J. C., Fagan C. J. Polycystic liver disease: a study of cyst fluid constituents. Hepatology. 1982 Jul-Aug;2(4):475–478. doi: 10.1002/hep.1840020414. [DOI] [PubMed] [Google Scholar]
  24. Ponzetto A., Cote P. J., Popper H., Hoyer B. H., London W. T., Ford E. C., Bonino F., Purcell R. H., Gerin J. L. Transmission of the hepatitis B virus-associated delta agent to the eastern woodchuck. Proc Natl Acad Sci U S A. 1984 Apr;81(7):2208–2212. doi: 10.1073/pnas.81.7.2208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ponzetto A., Forzani B., Smedile A., Hele C., Avanzini L., Novara R., Canese M. G. Acute and chronic delta infection in the woodchuck. Prog Clin Biol Res. 1987;234:37–46. [PubMed] [Google Scholar]
  26. Pugh J. C., Yaginuma K., Koike K., Summers J. Duck hepatitis B virus (DHBV) particles produced by transient expression of DHBV DNA in a human hepatoma cell line are infectious in vitro. J Virol. 1988 Sep;62(9):3513–3516. doi: 10.1128/jvi.62.9.3513-3516.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rizzetto M., Canese M. G., Gerin J. L., London W. T., Sly D. L., Purcell R. H. Transmission of the hepatitis B virus-associated delta antigen to chimpanzees. J Infect Dis. 1980 May;141(5):590–602. doi: 10.1093/infdis/141.5.590. [DOI] [PubMed] [Google Scholar]
  28. Rizzetto M., Hoyer B., Canese M. G., Shih J. W., Purcell R. H., Gerin J. L. delta Agent: association of delta antigen with hepatitis B surface antigen and RNA in serum of delta-infected chimpanzees. Proc Natl Acad Sci U S A. 1980 Oct;77(10):6124–6128. doi: 10.1073/pnas.77.10.6124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rizzetto M., Verme G. Delta hepatitis--present status. J Hepatol. 1985;1(2):187–193. doi: 10.1016/s0168-8278(85)80766-2. [DOI] [PubMed] [Google Scholar]
  30. Rizzetto M., Verme G., Recchia S., Bonino F., Farci P., Aricò S., Calzia R., Picciotto A., Colombo M., Popper H. Chronic hepatitis in carriers of hepatitis B surface antigen, with intrahepatic expression of the delta antigen. An active and progressive disease unresponsive to immunosuppressive treatment. Ann Intern Med. 1983 Apr;98(4):437–441. doi: 10.7326/0003-4819-98-4-437. [DOI] [PubMed] [Google Scholar]
  31. Saldanha J. A., Thomas H. C., Monjardino J. P. Cloning and characterisation of a delta virus cDNA sequence derived from a human source. J Med Virol. 1987 Aug;22(4):323–331. doi: 10.1002/jmv.1890220405. [DOI] [PubMed] [Google Scholar]
  32. Sharmeen L., Kuo M. Y., Dinter-Gottlieb G., Taylor J. Antigenomic RNA of human hepatitis delta virus can undergo self-cleavage. J Virol. 1988 Aug;62(8):2674–2679. doi: 10.1128/jvi.62.8.2674-2679.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Smedile A., Rizzetto M., Denniston K., Bonino F., Wells F., Verme G., Consolo F., Hoyer B., Purcell R. H., Gerin J. L. Type D hepatitis: the clinical significance of hepatitis D virus RNA in serum as detected by a hybridization-based assay. Hepatology. 1986 Nov-Dec;6(6):1297–1302. doi: 10.1002/hep.1840060612. [DOI] [PubMed] [Google Scholar]
  34. Taylor J., Mason W., Summers J., Goldberg J., Aldrich C., Coates L., Gerin J., Gowans E. Replication of human hepatitis delta virus in primary cultures of woodchuck hepatocytes. J Virol. 1987 Sep;61(9):2891–2895. doi: 10.1128/jvi.61.9.2891-2895.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wang K. S., Choo Q. L., Weiner A. J., Ou J. H., Najarian R. C., Thayer R. M., Mullenbach G. T., Denniston K. J., Gerin J. L., Houghton M. Structure, sequence and expression of the hepatitis delta (delta) viral genome. Nature. 1986 Oct 9;323(6088):508–514. doi: 10.1038/323508a0. [DOI] [PubMed] [Google Scholar]
  36. Will H., Reiser W., Weimer T., Pfaff E., Büscher M., Sprengel R., Cattaneo R., Schaller H. Replication strategy of human hepatitis B virus. J Virol. 1987 Mar;61(3):904–911. doi: 10.1128/jvi.61.3.904-911.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]

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