Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1994 Sep;68(9):5344–5350. doi: 10.1128/jvi.68.9.5344-5350.1994

Apparent helper-independent infection of woodchucks by hepatitis delta virus and subsequent rescue with woodchuck hepatitis virus.

H J Netter 1, J L Gerin 1, B C Tennant 1, J M Taylor 1
PMCID: PMC236934  PMID: 8057418

Abstract

Hepatitis delta virus (HDV) is a subviral agent of humans which is dependent upon hepatitis B virus as a helper for transmission. HDV can be experimentally transmitted to woodchucks by using woodchuck hepatitis virus (WHV) as the helper. We used this model system to study two types of HDV infections: those of animals already chronically infected with WHV and those of animals without any evidence of prior exposure to WHV. At 5 to 10 days after infection with HDV, liver biopsies of these two groups of animals indicated that around 1% of the hepatocytes were infected (HDV antigen positive). Moreover, similar amounts of replicative forms of HDV RNA were detected. In contrast, by 20 days postinfection, the two groups of animals were quite different in the extent of the HDV infection. The animals chronically infected with WHV showed spread of the infection within the liver and the release of high titers of HDV into the serum. In contrast, the animals not previously exposed to WHV showed a progressive reduction in liver involvement, and at no time up to 165 days postinfection could we detect HDV particles in the serum. However, if these animals were inoculated with a relatively high titer of WHV at either 7 or even 33 days after the HDV infection, HDV viremia was observed. Our data support the interpretation that in these animals, hepatocytes were initially infected in the absence of helper virus, HDV genome replication took place, and ultimately these replicating genomes were rescued by the secondary WHV infection. The observation that HDV can survive in the liver for at least 33 days in the absence of coinfecting helper virus may be relevant to the reemergence of HDV infection following liver transplantation.

Full text

PDF

Images in this article

Selected References

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

  1. Bichko V., Netter H. J., Taylor J. Introduction of hepatitis delta virus into animal cell lines via cationic liposomes. J Virol. 1994 Aug;68(8):5247–5252. doi: 10.1128/jvi.68.8.5247-5252.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bichko V., Schödel F., Nassal M., Gren E., Berzinsh I., Borisova G., Miska S., Peterson D. L., Gren E., Pushko P. Epitopes recognized by antibodies to denatured core protein of hepatitis B virus. Mol Immunol. 1993 Feb;30(3):221–231. doi: 10.1016/0161-5890(93)90051-c. [DOI] [PubMed] [Google Scholar]
  3. Chang F. L., Chen P. J., Tu S. J., Wang C. J., Chen D. S. The large form of hepatitis delta antigen is crucial for assembly of hepatitis delta virus. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8490–8494. doi: 10.1073/pnas.88.19.8490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cote P. J., Roneker C., Cass K., Schödel F., Peterson D., Tennant B., De Noronha F., Gerin J. New enzyme immunoassays for the serologic detection of woodchuck hepatitis virus infection. Viral Immunol. 1993 Summer;6(2):161–169. doi: 10.1089/vim.1993.6.161. [DOI] [PubMed] [Google Scholar]
  5. David E., Pucci A., Rahier J., Andorno E., Fassi L., Fortunato M., Fabiano A., Mollo F., Rizzetto M. Histopathology of recurrent delta hepatitis in liver transplant. Prog Clin Biol Res. 1993;382:419–424. [PubMed] [Google Scholar]
  6. Dourakis S., Karayiannis P., Goldin R., Taylor M., Monjardino J., Thomas H. C. An in situ hybridization, molecular biological and immunohistochemical study of hepatitis delta virus in woodchucks. Hepatology. 1991 Sep;14(3):534–539. [PubMed] [Google Scholar]
  7. Fu T. B., Taylor J. The RNAs of hepatitis delta virus are copied by RNA polymerase II in nuclear homogenates. J Virol. 1993 Dec;67(12):6965–6972. doi: 10.1128/jvi.67.12.6965-6972.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gowans E. J., Bonino F. Hepatitis delta virus pathogenicity. Prog Clin Biol Res. 1993;382:125–130. [PubMed] [Google Scholar]
  9. 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]
  10. MacNaughton T. B., Gowans E. J., McNamara S. P., Burrell C. J. Hepatitis delta antigen is necessary for access of hepatitis delta virus RNA to the cell transcriptional machinery but is not part of the transcriptional complex. Virology. 1991 Sep;184(1):387–390. doi: 10.1016/0042-6822(91)90855-6. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Negro F., Korba B. E., Forzani B., Baroudy B. M., Brown T. L., Gerin J. L., Ponzetto A. Hepatitis delta virus (HDV) and woodchuck hepatitis virus (WHV) nucleic acids in tissues of HDV-infected chronic WHV carrier woodchucks. J Virol. 1989 Apr;63(4):1612–1618. doi: 10.1128/jvi.63.4.1612-1618.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Netter H. J., Kajino K., Taylor J. M. Experimental transmission of human hepatitis delta virus to the laboratory mouse. J Virol. 1993 Jun;67(6):3357–3362. doi: 10.1128/jvi.67.6.3357-3362.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. 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]
  16. Ponzetto A., Negro F., Gerin J. L., Purcell R. H. Experimental hepatitis delta virus infection in the animal model. Prog Clin Biol Res. 1991;364:147–157. [PubMed] [Google Scholar]
  17. 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]
  18. Smedile A., Mangia A., Brunetto M. R., Giarin M., Marzano A., Ottobrelli A., Chiaberge E., Durazzo M., Bonino F., Verme G. Different aspects of HDV and HBV reinfections and liver disease in orthotopic liver transplant (OLT). Prog Clin Biol Res. 1993;382:393–402. [PubMed] [Google Scholar]
  19. Sureau C., Jacob J. R., Eichberg J. W., Lanford R. E. Tissue culture system for infection with human hepatitis delta virus. J Virol. 1991 Jul;65(7):3443–3450. doi: 10.1128/jvi.65.7.3443-3450.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Sureau C., Moriarty A. M., Thornton G. B., Lanford R. E. Production of infectious hepatitis delta virus in vitro and neutralization with antibodies directed against hepatitis B virus pre-S antigens. J Virol. 1992 Feb;66(2):1241–1245. doi: 10.1128/jvi.66.2.1241-1245.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Van Thiel D. H., Fagiuoli S., Wright H. I. Liver transplantation for viral hepatitis: the current situation. Prog Clin Biol Res. 1993;382:377–387. [PubMed] [Google Scholar]
  23. Zignego A. L., Samuel D., Gigou M., Feray C., Arulnaden J. L., Monti M., Gentilini P., Reynes M., Benhamou J. P., Brechot C. Patterns of hepatitis delta reinfection after liver transplantation and their evolution during a long term follow-up. Prog Clin Biol Res. 1993;382:409–417. [PubMed] [Google Scholar]

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

RESOURCES