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. 1995 Dec;69(12):7593–7600. doi: 10.1128/jvi.69.12.7593-7600.1995

Hepatitis D virus RNA editing: specific modification of adenosine in the antigenomic RNA.

J L Casey 1, J L Gerin 1
PMCID: PMC189698  PMID: 7494266

Abstract

RNA editing plays a central role in the life cycle of hepatitis D virus (HDV), a subviral human pathogen. Previous studies (J.L. Casey, K.F. Bergmann, T.L. Brown, and J.L. Gerin, Proc. Natl. Acad. Sci USA 89:7149-7153, 1992; H. Zheng, T.-B. Fu, D. Lazinski, and J. Taylor, J. Virol. 66:4693-4697, 1992) had concluded that the genomic RNA of HDV was the target for RNA editing and that the editing reaction was a conversion of U to C. However, we show here that the antigenomic RNA of HDV is in fact the target for HDV RNA editing, which is therefore a conversion of A to G. This result is verified by using an assay specific for editing on the antigenomic RNA and by analyzing the editing of site-directed mutant RNAs in transfected cells and in cell extracts. Because editing occurs in the absence of viral antigens and the specificity for the HDV editing target site is present even in extracts from Drosophila cells, it is likely that HDV RNA is edited by one or more cellular factors that are conserved among higher eukaryotes. These results raise the likelihood that double-stranded RNA adenosine deaminase specifically edits HDV antigenomic RNA.

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Selected References

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  1. Bass B. L., Weintraub H. An unwinding activity that covalently modifies its double-stranded RNA substrate. Cell. 1988 Dec 23;55(6):1089–1098. doi: 10.1016/0092-8674(88)90253-x. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. 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]
  4. Bonino F., Hoyer B., Nelson J., Engle R., Verme G., Gerin J. Hepatitis B virus DNA in the sera of HBsAg carriers: a marker of active hepatitis B virus replication in the liver. Hepatology. 1981 Sep-Oct;1(5):386–391. doi: 10.1002/hep.1840010503. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Casey J. L., Bergmann K. F., Brown T. L., Gerin J. L. Determinants of RNA editing in hepatitis delta virus. Prog Clin Biol Res. 1993;382:5–11. [PubMed] [Google Scholar]
  7. Casey J. L., Bergmann K. F., Brown T. L., Gerin J. L. Structural requirements for RNA editing in hepatitis delta virus: evidence for a uridine-to-cytidine editing mechanism. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):7149–7153. doi: 10.1073/pnas.89.15.7149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Casey J. L., Brown T. L., Colan E. J., Wignall F. S., Gerin J. L. A genotype of hepatitis D virus that occurs in northern South America. Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9016–9020. doi: 10.1073/pnas.90.19.9016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chang M. F., Sun C. Y., Chen C. J., Chang S. C. Functional motifs of delta antigen essential for RNA binding and replication of hepatitis delta virus. J Virol. 1993 May;67(5):2529–2536. doi: 10.1128/jvi.67.5.2529-2536.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Higuchi M., Single F. N., Köhler M., Sommer B., Sprengel R., Seeburg P. H. RNA editing of AMPA receptor subunit GluR-B: a base-paired intron-exon structure determines position and efficiency. Cell. 1993 Dec 31;75(7):1361–1370. doi: 10.1016/0092-8674(93)90622-w. [DOI] [PubMed] [Google Scholar]
  12. Hough R. F., Bass B. L. Purification of the Xenopus laevis double-stranded RNA adenosine deaminase. J Biol Chem. 1994 Apr 1;269(13):9933–9939. [PubMed] [Google Scholar]
  13. Kim U., Garner T. L., Sanford T., Speicher D., Murray J. M., Nishikura K. Purification and characterization of double-stranded RNA adenosine deaminase from bovine nuclear extracts. J Biol Chem. 1994 May 6;269(18):13480–13489. [PubMed] [Google Scholar]
  14. Kim U., Wang Y., Sanford T., Zeng Y., Nishikura K. Molecular cloning of cDNA for double-stranded RNA adenosine deaminase, a candidate enzyme for nuclear RNA editing. Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11457–11461. doi: 10.1073/pnas.91.24.11457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Lazinski D. W., Taylor J. M. Expression of hepatitis delta virus RNA deletions: cis and trans requirements for self-cleavage, ligation, and RNA packaging. J Virol. 1994 May;68(5):2879–2888. doi: 10.1128/jvi.68.5.2879-2888.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lazinski D. W., Taylor J. M. Relating structure to function in the hepatitis delta virus antigen. J Virol. 1993 May;67(5):2672–2680. doi: 10.1128/jvi.67.5.2672-2680.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Lomeli H., Mosbacher J., Melcher T., Höger T., Geiger J. R., Kuner T., Monyer H., Higuchi M., Bach A., Seeburg P. H. Control of kinetic properties of AMPA receptor channels by nuclear RNA editing. Science. 1994 Dec 9;266(5191):1709–1713. doi: 10.1126/science.7992055. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Macnaughton T. B., Beard M. R., Chao M., Gowans E. J., Lai M. M. Endogenous promoters can direct the transcription of hepatitis delta virus RNA from a recircularized cDNA template. Virology. 1993 Oct;196(2):629–636. doi: 10.1006/viro.1993.1519. [DOI] [PubMed] [Google Scholar]
  22. O'Connell M. A., Keller W. Purification and properties of double-stranded RNA-specific adenosine deaminase from calf thymus. Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10596–10600. doi: 10.1073/pnas.91.22.10596. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Peppel K., Baglioni C. A simple and fast method to extract RNA from tissue culture cells. Biotechniques. 1990 Dec;9(6):711–713. [PubMed] [Google Scholar]
  24. Polson A. G., Bass B. L. Preferential selection of adenosines for modification by double-stranded RNA adenosine deaminase. EMBO J. 1994 Dec 1;13(23):5701–5711. doi: 10.1002/j.1460-2075.1994.tb06908.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. 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]
  27. Rizzetto M. The delta agent. Hepatology. 1983 Sep-Oct;3(5):729–737. doi: 10.1002/hep.1840030518. [DOI] [PubMed] [Google Scholar]
  28. Ryu W. S., Bayer M., Taylor J. Assembly of hepatitis delta virus particles. J Virol. 1992 Apr;66(4):2310–2315. doi: 10.1128/jvi.66.4.2310-2315.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]
  30. Wagner R. W., Smith J. E., Cooperman B. S., Nishikura K. A double-stranded RNA unwinding activity introduces structural alterations by means of adenosine to inosine conversions in mammalian cells and Xenopus eggs. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2647–2651. doi: 10.1073/pnas.86.8.2647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Wang J. G., Cullen J., Lemon S. M. Immunoblot analysis demonstrates that the large and small forms of hepatitis delta virus antigen have different C-terminal amino acid sequences. J Gen Virol. 1992 Jan;73(Pt 1):183–188. doi: 10.1099/0022-1317-73-1-183. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. 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]
  34. Zheng H., Fu T. B., Lazinski D., Taylor J. Editing on the genomic RNA of human hepatitis delta virus. J Virol. 1992 Aug;66(8):4693–4697. doi: 10.1128/jvi.66.8.4693-4697.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]

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