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. 1989 Oct;63(10):4292–4297. doi: 10.1128/jvi.63.10.4292-4297.1989

Cloned hepatitis delta virus cDNA is infectious in the chimpanzee.

C Sureau 1, J Taylor 1, M Chao 1, J W Eichberg 1, R E Lanford 1
PMCID: PMC251044  PMID: 2778877

Abstract

A head-to-tail trimer of a full-length cDNA clone of the hepatitis delta virus (HDV) genome was examined for infectivity by direct inoculation into the liver of a chimpanzee that was already infected with hepatitis B virus. Five weeks after inoculation, a marked elevation of serum alanine aminotransferase activity was observed, followed by the appearance of high levels of HDV RNA and antigen in both liver and serum and a high level of viral particles in the serum. A transient suppression of hepatitis B virus replication was evident during the acute phase of HDV infection. Seroconversion for antibodies to delta antigen occurred 3 weeks after the onset of the disease. These results demonstrate that a typical HDV infection can be initiated by inoculation of a susceptible animal with recombinant HDV cDNA.

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Selected References

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

  1. Bergmann K. F., Gerin J. L. Antigens of hepatitis delta virus in the liver and serum of humans and animals. J Infect Dis. 1986 Oct;154(4):702–706. doi: 10.1093/infdis/154.4.702. [DOI] [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. Bonino F., Hoyer B., Shih J. W., Rizzetto M., Purcell R. H., Gerin J. L. Delta hepatitis agent: structural and antigenic properties of the delta-associated particle. Infect Immun. 1984 Mar;43(3):1000–1005. doi: 10.1128/iai.43.3.1000-1005.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Branch A. D., Benenfeld B. J., Baroudy B. M., Wells F. V., Gerin J. L., Robertson H. D. An ultraviolet-sensitive RNA structural element in a viroid-like domain of the hepatitis delta virus. Science. 1989 Feb 3;243(4891):649–652. doi: 10.1126/science.2492676. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Branch A. D., Robertson H. D., Dickson E. Longer-than-unit-length viroid minus strands are present in RNA from infected plants. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6381–6385. doi: 10.1073/pnas.78.10.6381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chang M. F., Baker S. C., Soe L. H., Kamahora T., Keck J. G., Makino S., Govindarajan S., Lai M. M. Human hepatitis delta antigen is a nuclear phosphoprotein with RNA-binding activity. J Virol. 1988 Jul;62(7):2403–2410. doi: 10.1128/jvi.62.7.2403-2410.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chen P. J., Chen D. S., Chen C. R., Chen Y. Y., Chen H. M., Lai M. Y., Sung J. L. Delta infection in asymptomatic carriers of hepatitis B surface antigen: low prevalence of delta activity and effective suppression of hepatitis B virus replication. Hepatology. 1988 Sep-Oct;8(5):1121–1124. doi: 10.1002/hep.1840080525. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Cress D. E., Kiefer M. C., Owens R. A. Construction of infectious potato spindle tuber viroid cDNA clones. Nucleic Acids Res. 1983 Oct 11;11(19):6821–6835. doi: 10.1093/nar/11.19.6821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Diener T. O. Viroid processing: a model involving the central conserved region and hairpin I. Proc Natl Acad Sci U S A. 1986 Jan;83(1):58–62. doi: 10.1073/pnas.83.1.58. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Genesca J., Jardi R., Buti M., Vives L., Prat S., Esteban J. I., Esteban R., Guardia J. Hepatitis B virus replication in acute hepatitis B, acute hepatitis B virus-hepatitis delta virus coinfection and acute hepatitis delta superinfection. Hepatology. 1987 May-Jun;7(3):569–572. doi: 10.1002/hep.1840070325. [DOI] [PubMed] [Google Scholar]
  14. Ichimura H., Tamura I., Tsubakio T., Kurimura O., Kurimura T. Influence of hepatitis delta virus superinfection on the clearance of hepatitis B virus (HBV) markers in HBV carriers in Japan. J Med Virol. 1988 Sep;26(1):49–55. doi: 10.1002/jmv.1890260108. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Krogsgaard K., Aldershvile J., Kryger P., Andersson P., Nielsen J. O., Hansson B. G. Hepatitis B virus DNA, HBeAg and delta infection during the course from acute to chronic hepatitis B virus infection. Hepatology. 1985 Sep-Oct;5(5):778–782. doi: 10.1002/hep.1840050512. [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., Chao M., Taylor J. Initiation of replication of the human hepatitis delta virus genome from cloned DNA: role of delta antigen. J Virol. 1989 May;63(5):1945–1950. doi: 10.1128/jvi.63.5.1945-1950.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Kuo M. Y., Sharmeen L., Dinter-Gottlieb G., Taylor J. Characterization of self-cleaving RNA sequences on the genome and antigenome of human hepatitis delta virus. J Virol. 1988 Dec;62(12):4439–4444. doi: 10.1128/jvi.62.12.4439-4444.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. O'Rear J. J., Mizutani S., Hoffman G., Fiandt M., Temin H. M. Infectious and noninfectious recombinant clones of the provirus of SNV differ in cellular DNA and are apparently the same in viral DNA. Cell. 1980 Jun;20(2):423–430. doi: 10.1016/0092-8674(80)90628-5. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Ponzetto A., Hoyer B. H., Popper H., Engle R., Purcell R. H., Gerin J. L. Titration of the infectivity of hepatitis D virus in chimpanzees. J Infect Dis. 1987 Jan;155(1):72–78. doi: 10.1093/infdis/155.1.72. [DOI] [PubMed] [Google Scholar]
  25. Racaniello V. R., Baltimore D. Cloned poliovirus complementary DNA is infectious in mammalian cells. Science. 1981 Nov 20;214(4523):916–919. doi: 10.1126/science.6272391. [DOI] [PubMed] [Google Scholar]
  26. Rasshofer R., Buti M., Esteban R., Jardi R., Roggendorf M. Demonstration of hepatitis D virus RNA in patients with chronic hepatitis. J Infect Dis. 1988 Jan;157(1):191–195. doi: 10.1093/infdis/157.1.191. [DOI] [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., Morello C., Mannucci P. M., Gocke D. J., Spero J. A., Lewis J. H., Van Thiel D. H., Scaroni C., Peyretti F. Delta infection and liver disease in hemophilic carriers of hepatitis B surface antigen. J Infect Dis. 1982 Jan;145(1):18–22. doi: 10.1093/infdis/145.1.18. [DOI] [PubMed] [Google Scholar]
  30. Rizzetto M. The delta agent. Hepatology. 1983 Sep-Oct;3(5):729–737. doi: 10.1002/hep.1840030518. [DOI] [PubMed] [Google Scholar]
  31. Rizzetto M., Verme G., Gerin J. L., Purcell R. H. Hepatitis delta virus disease. Prog Liver Dis. 1986;8:417–431. [PubMed] [Google Scholar]
  32. Roggendorf M., Pahlke C., Böhm B., Rasshofer R. Characterization of proteins associated with hepatitis delta virus. J Gen Virol. 1987 Nov;68(Pt 11):2953–2959. doi: 10.1099/0022-1317-68-11-2953. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. 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]
  35. Sharmeen L., Kuo M. Y., Taylor J. Self-ligating RNA sequences on the antigenome of human hepatitis delta virus. J Virol. 1989 Mar;63(3):1428–1430. doi: 10.1128/jvi.63.3.1428-1430.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  37. Sprengel R., Kuhn C., Manso C., Will H. Cloned duck hepatitis B virus DNA is infectious in Pekin ducks. J Virol. 1984 Dec;52(3):932–937. doi: 10.1128/jvi.52.3.932-937.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Sureau C., Romet-Lemonne J. L., Mullins J. I., Essex M. Production of hepatitis B virus by a differentiated human hepatoma cell line after transfection with cloned circular HBV DNA. Cell. 1986 Oct 10;47(1):37–47. doi: 10.1016/0092-8674(86)90364-8. [DOI] [PubMed] [Google Scholar]
  39. Tabler M., Sänger H. L. Cloned single- and double-stranded DNA copies of potato spindle tuber viroid (PSTV) RNA and co-inoculated subgenomic DNA fragments are infectious. EMBO J. 1984 Dec 20;3(13):3055–3062. doi: 10.1002/j.1460-2075.1984.tb02257.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Taniguchi T., Palmieri M., Weissmann C. QB DNA-containing hybrid plasmids giving rise to QB phage formation in the bacterial host. Nature. 1978 Jul 20;274(5668):223–228. doi: 10.1038/274223a0. [DOI] [PubMed] [Google Scholar]
  41. 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]
  42. Weiner A. J., Choo Q. L., Wang K. S., Govindarajan S., Redeker A. G., Gerin J. L., Houghton M. A single antigenomic open reading frame of the hepatitis delta virus encodes the epitope(s) of both hepatitis delta antigen polypeptides p24 delta and p27 delta. J Virol. 1988 Feb;62(2):594–599. doi: 10.1128/jvi.62.2.594-599.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Will H., Cattaneo R., Darai G., Deinhardt F., Schellekens H., Schaller H. Infectious hepatitis B virus from cloned DNA of known nucleotide sequence. Proc Natl Acad Sci U S A. 1985 Feb;82(3):891–895. doi: 10.1073/pnas.82.3.891. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Will H., Cattaneo R., Koch H. G., Darai G., Schaller H., Schellekens H., van Eerd P. M., Deinhardt F. Cloned HBV DNA causes hepatitis in chimpanzees. Nature. 1982 Oct 21;299(5885):740–742. doi: 10.1038/299740a0. [DOI] [PubMed] [Google Scholar]
  45. Wu H. N., Lai M. M. Reversible cleavage and ligation of hepatitis delta virus RNA. Science. 1989 Feb 3;243(4891):652–654. doi: 10.1126/science.2492677. [DOI] [PubMed] [Google Scholar]

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