1887

Abstract

The hepatitis delta vims (HDV) genome consists of circular ssRNA which has extensive intramolecular complementarity and can form a dsRNA rod-like stmcture. If such RNA species were to exist in an unmasked form in cells, they would be expected to induce interferon (IFN) expression and activate two IFN-inducible dsRNA-dependent enzymes with antiviral activity, namely the dsRNA-dependent protein kinase (PKR) and 2′,5′ oligoadenylate (2′,5′A) synthetase. Since the vims replicates to high copy number for prolonged periods in infected cells it is apparently able to evade these antiviral mechanisms. The RNA genome may be masked and fail to induce or activate the antiviral response, or the vims may inhibit such a response. Treatment of a hepatoma cell line, Huh7, and a fibrosarcoma cell line, HT1080, stably transfected with a trimeric HDV cDNA constmct, with IFN- or IFN- for up to seven days failed to influence the level of expression of genomic or antigenomic HDV RNA, or delta antigen (Ag). This is consistent with either failure of activation or inhibition of the IFN response. However the induction of several IFN-responsive genes, including PKR, 2′,5′A synthetase and class I MHC is normal and cotransfection of a constmct expressing delta Ag did not affect expression from an IFN-inducible chloramphenicol acetyltransferase constmct. In addition, the activation of PKR is not inhibited in HDV-expressing cells and antiviral assays suggest that the ability of these cells to mount an antiviral response to at least two cytopathic vimses is unaffected. IFN- is inducible normally by dsRNA in cells transfected with the delta cDNA trimer. We conclude that HDV replication is not inhibited by IFN- or IFN-, even though the responses of cells expressing HDV RNA and antigen to IFN and dsRNA are intact.

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1994-06-01
2022-01-20
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References

  1. Ackrill A. M., Foster G. R., Laxton C. D., Flavell D. M., Stark G. R., Kerr I. M. 1991; Inhibition of the cellular response to interferons by products of the adenovirus type 5 El A oncogene. Nucleic Acids Research 19:4387–4393
    [Google Scholar]
  2. Bergmann K. F., Gerin J. L. 1986; Antigens of hepatitis delta virus in the liver and serum of humans and animals. Journal of Infectious Diseases 154:702–705
    [Google Scholar]
  3. Bonino F., Heermann K. H., Rizzetto M., Gerlich W. H. 1986; Flepatitis delta virus: protein composition of delta antigen and its hepatitis B virus-derived envelope. Journal of Virology 58:945–950
    [Google Scholar]
  4. Casey J. L., Bergman K. F., Brown T. L., Gerin J. L. 1992; Structural requirements for RNA editing in hepatitis delta virus: evidence for a uridine to cytidine editing mechanism. Proceedings of the National Academy of Sciences U.S.A.: 897149–7153
    [Google Scholar]
  5. Chang F. L., Chen P. J., Tu S. J., Wang C. J., Chen D. S. 1991; The large form of hepatitis 5 antigen is crucial for assembly of hepatitis δ virus. Proceedings of the National Academy of Sciences U.S.A.: 888490–8494
    [Google Scholar]
  6. Chang M.-F., Baker S. C., Soe L. H., Kamahora T., Keck J. G., Shinji M., Govindarajan S., Lai M. M. C. 1988; Human hepatitis delta virus antigen is a nuclear phosphoprotein with RNA-binding activity. Journal of Virology 62:2403–2410
    [Google Scholar]
  7. Chao M., Hsieh S. Y., Taylor J. 1990; Role of two forms of hepatitis delta virus antigen: evidence for a mechanism of selflimiting genome replication. Journal of Virology 64:5066–5069
    [Google Scholar]
  8. Chao M., Hsieh S.-Y., Taylor J. 1991; The antigen of hepatitis delta virus: examination of in vitro RNA-binding specificity. Journal of Virology 65:4057–4062
    [Google Scholar]
  9. Chen P.-J., Kalpana G., Goldberg J., Mason W., Werner B., Gerin J., Taylor J. 1986; Structure and replication of the genome of the hepatitis S virus. Proceedings of the National Academy of Sciences U.S.A.: 838774–8778
    [Google Scholar]
  10. Cheng D. J., Yang A., Thomas H. C., Monjardino J. 1992; Characterisation of a stable hepatitis delta antigen expressing cell line: effect of delta antigen on cell growth. In Hepatitis Delta Virus: Molecular Biology, Pathogenesis and Clinical Aspects pp 149–153 Taylor J. Edited by New York: Wiley Liss;
    [Google Scholar]
  11. Clemens M. J., Hershey J. W. B., Hovanessian A. G., Katze M. G., Kaufman R. J., Lengyel P., Samuel C. E., Sen G. S., Williams B. R. G. 1993; PKR: proposed nomenclature for the RNA-dependent protein kinase induced by interferon. Journal of Interferon Research 13:241
    [Google Scholar]
  12. De-Benedetti A., Baglioni C. 1984; Inhibition of mRNA binding to ribosomes by localized activation of dsRNA-dependent protein kinase. Nature; London: 31179–81
    [Google Scholar]
  13. Demaeyer E., De Maeyer-Guignard J. 1988 Interferons and Other Regulatory Cytokines Chichester: John Wiley & Sons;
    [Google Scholar]
  14. Farci P., Karayiannis P., Brook M. G., Smedile A., Lai M. E., Balestrieri A., Saldanha J. A., Monjardino J., Gerin J., Thomas H. C. 1989; Treatment of chronic hepatitis delta virus (HDV) infection with human lymphoblastoid interferon. Quarterly Journal of Medicine 73:1045–1054
    [Google Scholar]
  15. Glenn J. S., White J. M. 1991; Trans-dominant inhibition of human hepatitis delta virus genome replication. Journal of Virology 65:2357–2361
    [Google Scholar]
  16. Gowans E. J., Baroudy B. M., Negro G., Ponzetto A., Purcell R. H., Gerin J. L. 1988; Evidence for replication of hepatitis delta virus RNA in hepatocyte nuclei after in vivo infection. Virology 167:274–278
    [Google Scholar]
  17. Gutch M. J., Reich N. C. 1991; Repression of the interferon signal transduction pathway by the adenovirus El A oncogene. Proceedings of the National Academy of Sciences U.S.A.: 887913–7917
    [Google Scholar]
  18. Ho M. 1984; Induction and inducers of interferon. In Interferon 1, General and Applied Aspects pp 79–124 Billiau A. Edited by Amsterdam: Elsevier;
    [Google Scholar]
  19. Hovanessian A. 1989; The double-stranded RNA-activated protein kinase induced by interferon: dsRNA-PK. Journal of Interferon Research 9:641–647
    [Google Scholar]
  20. Kalvakolanu D. V. R., Bandyopadhyay S. K., Harter M. L., Sen G. C. 1991; Inhibition of interferon-inducible gene expression by adenovirus El A proteins: block in transcriptional complex formation. Proceedings of the National Academy of Sciences U.S.A: 887459–7463
    [Google Scholar]
  21. Karayiannis P., Goldin R., Luther S., Carman W. F., Mon-Jardino J., Thomas H. C. 1992; Effect of cyclosporin A in woodchucks with chronic hepatitis delta virus infection. Journal of Medical Virology 36:316–321
    [Google Scholar]
  22. Kerr I. M. 1987; The 2-5A system: a personal view. Journal of Interferon Research 7:505–510
    [Google Scholar]
  23. Kuo M. Y.-P., Goldberg J., Coates L., Mason W., Gerin J., Taylor J. 1988a; Molecular cloning of hepatitis delta virus RNA from an infected woodchuck liver: sequence, structure and applications. Journal of Virology 62:1855–1761
    [Google Scholar]
  24. Kuo M.Y.-P., Sharmeen L., Dinter-Gottlieb G., Taylor J. 1988b; Characterization of self-cleaving RNA sequences on the genome and antigenome of human hepatitis delta virus. Journal of Virology 62:4439–4444
    [Google Scholar]
  25. Kuo M.Y.-P., Chao M., Taylor I. 1989; Initiation of replication of the human hepatitis delta virus genome from cloned DNA: role of delta antigen. Journal of Virology 63:1945–1950
    [Google Scholar]
  26. Laemmli U. K. 1970; Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature; London: 111680–685
    [Google Scholar]
  27. Lengyel P. 1982; Biochemistry of interferons and their actions. Annual Review of Biochemistry 51:251–282
    [Google Scholar]
  28. Luo G., Chao M., Hsieh S.-H., Sureau C., Nishikura K., Taylor J. 1990; A specific base transition occurs on replicating hepatitis delta virus RNA. Journal of Virology 64:1021–1027
    [Google Scholar]
  29. McNair A. N. B., Kerr I. M. 1993; Viral inhibition of the interferon system. Pharmacology and Therapeutics 56:79–95
    [Google Scholar]
  30. MacNaughton T. B., Gowans E. J., McNamara S. P., Burrell C. J. 1991; 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 184:387–390
    [Google Scholar]
  31. Porres J. C., Carreno V., Bartoleme J., Moreno A., Galiana F., Quiroga J. A. 1989; Treatment of chronic delta infection with recombinant human interferon alpha-2c at high doses. Journal of Hepatology 9:338–344
    [Google Scholar]
  32. Porter A. C. G., Chernajovsky Y., Dale T. C., Gilbert C. S., Stark G. R., Kerr I. M. 1988; Interferon response element of the human gene 6-16. EM BO Journal 7:85–92
    [Google Scholar]
  33. Rizzetto M. 1983; The delta agent. Hepatology 3:729–737
    [Google Scholar]
  34. Rizzetto M., Hoyer B., Canese M. G., Shih J. W.-K., Purcell R. H., Gerin J. L. 1980; Delta agent: association of delta antigen with hepatitis B surface antigen and RNA in serum of delta-infected chimpanzees. Proceedings of the National Academy of Sciences U.S.A.: 776124–6128
    [Google Scholar]
  35. Saldanha J., Homer E., Goldin R., Thomas H. C., Monjardino J. 1990; Cloning and expression of an immunodominant region of the hepatitis delta antigen. Journal of General Virology 71:471–175
    [Google Scholar]
  36. Sambrook J., Fritsch E. F., Maniatis T. 1989; . Molecular Cloning: A Laboratory Manual, 2nd edn.. New York: Cold Spring Harbor Laboratory;
    [Google Scholar]
  37. Samuel C. E. 1979; Mechanism of interferon action: phosphorylation of protein synthesis initiation factor eIF2 in interferon-treated human cells by a ribosome-associated kinase processing site with specificity similar to hemin-regulated rabbit reticulocyte kinase. Proceedings of the National Academy of Sciences U.S.A: 76600–604
    [Google Scholar]
  38. Sharmeen L., Kuo M.Y.-P., Dinter-Gottlieb G., Taylor J. 1988; Antigenome RNA of human hepatitis delta virus can undergo self-cleavage. Journal of Virology 62:2674–2679
    [Google Scholar]
  39. Silverman R. H., Watling D., Balkwill F., Trowsdale J., Kerr I. M. 1982a; The ppp(A2′p)A and protein kinase systems in wild-type and interferon-resistant Daudi cells. European Journal of Biochemistry 126:333–341
    [Google Scholar]
  40. Silverman R. H., Cayley P. J., Knight M., Gilbert C. S., Kerr I. M. 1982b; Control of the ppp(A2′p)nA system in HeLa cells-effects of interferon and virus infection. European Journal of Biochemistry 124:131–138
    [Google Scholar]
  41. Sleigh M. J. 1986; A non-chromatographic assay for expression of the chloramphenicol acetyl transferase gene in eucaryotic cells. Analytical Biochemistry 156:251–256
    [Google Scholar]
  42. Twu J., Lee C., Lin P., Schloemer R. 1988; Hepatitis B virus suppresses expression of human beta-interferon. Proceedings of the National Academy of Sciences U.S.A.: 85252–256
    [Google Scholar]
  43. 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. 1986; Structure sequence and expression of the hepatitis delta viral genome. Nature; London: 323508–514
    [Google Scholar]
  44. Whitten T., Quets A., Schloemer R. 1991; Identification of the hepatitis B virus factor that inhibits expression of the beta interferon gene. Journal of Virology 65:4699–1704
    [Google Scholar]
  45. Zheng H., Fu T.-B., Lazinski D., Taylor J. 1992; Editing on the genomic RNA of human hepatitis delta virus. Journal of Virology 66:4693–1697
    [Google Scholar]
  46. Zinn K., DiMaio D., Maniatis T. 1983; Identification of two distinct regulatory regions adjacent to the human β-interferon gene. Cell 34:865–879
    [Google Scholar]
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