Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Oct 1;88(19):8490–8494. doi: 10.1073/pnas.88.19.8490

The large form of hepatitis delta antigen is crucial for assembly of hepatitis delta virus.

F L Chang 1, P J Chen 1, S J Tu 1, C J Wang 1, D S Chen 1
PMCID: PMC52534  PMID: 1924308

Abstract

The virions of hepatitis delta virus (HDV) contain two species of HDV-specific protein, a large and a small form of hepatitis delta antigen (HDAg). We examined the role of individual HDAgs in virion assembly in cotransfection experiments. First, we constructed a replication-competent HDV mutant expressing only the small HDAg. When cotransfected with a plasmid expressing hepatitis B virus surface antigens to the HuH-7 cells, the mutant did not produce HDV virions, whereas the wild-type HDV clone did. Therefore, though the small HDAg is important for viral replication and is incorporated into the virus, the small-form delta antigen by itself is insufficient for virion formation. When the system was co-transfected with an additional plasmid providing the large HDAg, the HDV virion was then recovered. There was also evidence suggesting that the large HDAg could be copackaged into the HBsAg particles, without the presence of the HDV genome and the small HDAg. The results indicate a crucial role of the large HDAg in HDV assembly.

Full text

PDF
8490

Images in this article

8491Image
on p.8491
8492Image
on p.8492
8492Image
on p.8492
8492Image
on p.8492
8492Image
on p.8492
8492Image
on p.8492
8493Image
on p.8493
8493Image
on p.8493
8493Image
on p.8493
8494Image
on p.8494
8494Image
on p.8494
8494Image
on p.8494
8494Image
on p.8494
8494Image
on p.8494

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. Chao M., Hsieh S. Y., Taylor J. Role of two forms of hepatitis delta virus antigen: evidence for a mechanism of self-limiting genome replication. J Virol. 1990 Oct;64(10):5066–5069. doi: 10.1128/jvi.64.10.5066-5069.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chao Y. C., Chang M. F., Gust I., Lai M. M. Sequence conservation and divergence of hepatitis delta virus RNA. Virology. 1990 Oct;178(2):384–392. doi: 10.1016/0042-6822(90)90335-o. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Chen P. J., Kuo M. Y., Chen M. L., Tu S. J., Chiu M. N., Wu H. L., Hsu H. C., Chen D. S. Continuous expression and replication of the hepatitis delta virus genome in Hep G2 hepatoblastoma cells transfected with cloned viral DNA. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5253–5257. doi: 10.1073/pnas.87.14.5253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Higuchi R., Krummel B., Saiki R. K. A general method of in vitro preparation and specific mutagenesis of DNA fragments: study of protein and DNA interactions. Nucleic Acids Res. 1988 Aug 11;16(15):7351–7367. doi: 10.1093/nar/16.15.7351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Lin J. H., Chang M. F., Baker S. C., Govindarajan S., Lai M. M. Characterization of hepatitis delta antigen: specific binding to hepatitis delta virus RNA. J Virol. 1990 Sep;64(9):4051–4058. doi: 10.1128/jvi.64.9.4051-4058.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Luo G. X., Chao M., Hsieh S. Y., Sureau C., Nishikura K., Taylor J. A specific base transition occurs on replicating hepatitis delta virus RNA. J Virol. 1990 Mar;64(3):1021–1027. doi: 10.1128/jvi.64.3.1021-1027.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Rizzetto M., Canese M. G., Aricò S., Crivelli O., Trepo C., Bonino F., Verme G. Immunofluorescence detection of new antigen-antibody system (delta/anti-delta) associated to hepatitis B virus in liver and in serum of HBsAg carriers. Gut. 1977 Dec;18(12):997–1003. doi: 10.1136/gut.18.12.997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Sureau C., Taylor J., Chao M., Eichberg J. W., Lanford R. E. Cloned hepatitis delta virus cDNA is infectious in the chimpanzee. J Virol. 1989 Oct;63(10):4292–4297. doi: 10.1128/jvi.63.10.4292-4297.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Taylor J. M. Hepatitis delta virus: cis and trans functions required for replication. Cell. 1990 May 4;61(3):371–373. doi: 10.1016/0092-8674(90)90516-h. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. 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]
  18. Wu J. C., Chen P. J., Kuo M. Y., Lee S. D., Chen D. S., Ting L. P. Production of hepatitis delta virus and suppression of helper hepatitis B virus in a human hepatoma cell line. J Virol. 1991 Mar;65(3):1099–1104. doi: 10.1128/jvi.65.3.1099-1104.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Xia Y. P., Chang M. F., Wei D., Govindarajan S., Lai M. M. Heterogeneity of hepatitis delta antigen. Virology. 1990 Sep;178(1):331–336. doi: 10.1016/0042-6822(90)90415-n. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES