Abstract
The hepatitis delta virus can be found in the serum and liver of some hepatitis B virus patients. We now report that the RNA genome of serum-derived delta virus is single-stranded and circular. Livers of infected chimpanzees or woodchucks contained as many as 300,000 copies of genomic strand RNA per average cell, and at least some of this RNA had a circular conformation. Also present in the livers were RNA species complementary to the virion RNA. The genomic RNA was 5-22 times more abundant than this antigenomic strand. Some of the antigenomic RNA was complexed with genomic RNA, as evidenced by the fact that at least 34% of the antigenomic RNA was resistant to digestion with either RNase A in 0.3 M NaCl or S1 nuclease. Some of the antigenomic RNA was in a circular conformation. These and other findings showed that the structure and replication of hepatitis delta virus are in many ways similar to those of the previously described plant viroids, virusoids, and satellite RNAs.
Full text
PDF![8774](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2224/387014/f370795e6e33/pnas00326-0347.png)
![8775](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2224/387014/68e7b2182977/pnas00326-0348.png)
![8776](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2224/387014/c516e5a5cd8c/pnas00326-0349.png)
![8777](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2224/387014/4ffc08f8c817/pnas00326-0350.png)
![8778](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2224/387014/30da51565a00/pnas00326-0351.png)
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Baltimore D. Structure of the poliovirus replicative intermediate RNA. J Mol Biol. 1968 Mar 14;32(2):359–368. doi: 10.1016/0022-2836(68)90015-6. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Cattaneo R., Will H., Schaller H. Hepatitis B virus transcription in the infected liver. EMBO J. 1984 Sep;3(9):2191–2196. doi: 10.1002/j.1460-2075.1984.tb02113.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
- Chu F. K., Maley G. F., West D. K., Belfort M., Maley F. Characterization of the intron in the phage T4 thymidylate synthase gene and evidence for its self-excision from the primary transcript. Cell. 1986 Apr 25;45(2):157–166. doi: 10.1016/0092-8674(86)90379-x. [DOI] [PubMed] [Google Scholar]
- 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]
- Diener T. O. Viroids. Adv Virus Res. 1983;28:241–283. doi: 10.1016/s0065-3527(08)60725-3. [DOI] [PubMed] [Google Scholar]
- Donis-Keller H., Maxam A. M., Gilbert W. Mapping adenines, guanines, and pyrimidines in RNA. Nucleic Acids Res. 1977 Aug;4(8):2527–2538. doi: 10.1093/nar/4.8.2527. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Francki R. I. Plant virus satellites. Annu Rev Microbiol. 1985;39:151–174. doi: 10.1146/annurev.mi.39.100185.001055. [DOI] [PubMed] [Google Scholar]
- Hoyer B., Bonino F., Ponzetto A., Denniston K., Nelson J., Purcell R., Gerin J. L. Properties of delta-associated ribonucleic acid. Prog Clin Biol Res. 1983;143:91–97. [PubMed] [Google Scholar]
- Hsu T. W., Taylor J. M., Aldrich C., Townsend J. B., Seal G., Mason W. S. Tandem duplication of the proviral DNA in an avian sarcoma virus-transformed quail clone. J Virol. 1981 Apr;38(1):219–223. doi: 10.1128/jvi.38.1.219-223.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mason W. S., Aldrich C., Summers J., Taylor J. M. Asymmetric replication of duck hepatitis B virus DNA in liver cells: Free minus-strand DNA. Proc Natl Acad Sci U S A. 1982 Jul;79(13):3997–4001. doi: 10.1073/pnas.79.13.3997. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Riesner D., Gross H. J. Viroids. Annu Rev Biochem. 1985;54:531–564. doi: 10.1146/annurev.bi.54.070185.002531. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- Sorge J., West C., Westwood B., Beutler E. Molecular cloning and nucleotide sequence of human glucocerebrosidase cDNA. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7289–7293. doi: 10.1073/pnas.82.21.7289. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Taylor J. M., Faras A. J., Varmus H. E., Levinson W. E., Bishop J. M. Ribonucleic acid directed deoxyribonucleic acid synthesis by the purified deoxyribonucleic acid polymerase of Rous sarcoma virus. Characterization of the enzymatic product. Biochemistry. 1972 Jun 6;11(12):2343–2351. doi: 10.1021/bi00762a021. [DOI] [PubMed] [Google Scholar]
- Taylor J. M., Illmensee R., Summers J. Efficeint transcription of RNA into DNA by avian sarcoma virus polymerase. Biochim Biophys Acta. 1976 Sep 6;442(3):324–330. doi: 10.1016/0005-2787(76)90307-5. [DOI] [PubMed] [Google Scholar]
- Zaug A. J., Cech T. R. Oligomerization of intervening sequence RNA molecules in the absence of proteins. Science. 1985 Sep 13;229(4718):1060–1064. doi: 10.1126/science.2412290. [DOI] [PubMed] [Google Scholar]