1887

Abstract

SUMMARY

Highly passaged defective-interfering (DI) particle preparations of equine herpesvirus type 1 (EHV-1) were found to mediate the co-establishment of persistent infection and oncogenic transformation of permissive hamster embryo cells. Four cell lines, designated DI-1 to DI-4, were shown to possess biological properties typical of transformed cells and to induce the rapid formation of metastatic fibrosarcomas when injected into syngeneic LSH hamsters. Corresponding DI tumour cell lines, designated DI-1T to DI-4T, were found to be virus non-producing, to be transplantable in the hamster, and, like the four parent DI cell lines, to express EHV-1-coded antigens and to be resistant to superinfection with EHV-1 but not with a heterologous virus, vesicular stomatitis virus. All transformed cell lines, but not the tumour cell lines, contained a population of cells (2.6 to 9%) that continued to release infectious virus after 100 passages in culture. The production of interferon and selection of temperature-sensitive mutants did not appear to play a role in the maintenance of persistent infection. However, it was demonstrated that these persistently infected cells continued to release not only infectious virus but also DI particles after more than 2 years in culture. DI particles were shown to be present in released virus by: (i) detection of the defective virus DNA species (density 1.724 g/ml; standard EHV-1, density 1.716 g/ml) by CsCl analytical ultracentrifugation techniques; (ii) measurement of interference activity of virus released from DI-1 to DI-4 cells against standard EHV-1 replication; (iii) the presence of the 35 megadalton II fragment unique to the DI particle genome in DNA of released virus. These studies indicate that herpesvirus DI particles may function both in the initiation and maintenance of persistent infection and alter the cytocidal effects of infection to allow the establishment of oncogenic transformation and persistent infection.

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1982-05-01
2024-12-08
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References

  1. Ahmed R., Chakraborty P. R., Graham A. F., Ramig R. F., Fields B. N. 1980; Genetic variation during persistent reovirus infection: presence of extragenically suppressed temperature-sensitive lesions in wild-type virus isolated from persistently infected L cells. Journal of Virology 34:383–389
    [Google Scholar]
  2. Andzhaparidze O. G., Bogomolova N. N., BoriskiN Y. S., Bektemirova M. S., Drynov I. D. 1981; Comparative study of rabies virus persistence in human and hamster cell lines. Journal of Virology 37:1–6
    [Google Scholar]
  3. Campbell D. E., Kemp M. C., Perdue M. L., Randall C. C., Gentry G. A. 1976; Equine herpesvirus in vivo: cyclic production of a DNA density variant with repetitive sequences. Virology 69:737–750
    [Google Scholar]
  4. Cohen J. C., Randall C. C., O’callaghan D. J. 1975; Transcription of equine herpesvirus type 1: evidence for classes of transcripts differing in abundance. Virology 68:561–565
    [Google Scholar]
  5. Dal Canto M. C., Rabinowitz S. G. 1981; Murine central nervous system infection by a viral temperature-sensitive mutant. American Journal of Pathology 102:412–426
    [Google Scholar]
  6. De B. K., Nayak D. P. 1980; Defective interfering influenza viruses and host cells: establishment and maintenance of persistent influenza virus infection in MDBK and HeLa cells. Journal of Virology 36:847–859
    [Google Scholar]
  7. Dulbecco R., Vogt M. 1960; Significance of continued virus production in tissue culture rendered neoplastic by polyoma virus. Proceedings of the National Academy of Sciences of the United States of America 48:1617–1632
    [Google Scholar]
  8. Enzmann P. J. 1973; Induction of an interferon-like substance in persistently infected Aedes albopictus cells. Archivfur diegesamte Virusforschung 40:382–389
    [Google Scholar]
  9. Epstein M. S., Achong B. G. 1977; Recent progress in Epstein–Barr virus research. Annual Review of Microbiology 31:421–445
    [Google Scholar]
  10. Geder L., Lausch R., O’neill F., Rapp F. 1976; Oncogenic transformation of human embryo lung cells by human cytomegalovirus. Science 192:1134–1137
    [Google Scholar]
  11. Girardi A. J., Weinstein D., Koprowski H. 1965; SV40-induced transformation of human diploid cells: crisis and recovery. Journal of Cellular and Comparative Physiology 64:69–84
    [Google Scholar]
  12. Glasgow L. A., Habel K. 1962; The role of interferon in vaccinia virus infection of mouse embryo tissue culture. Journal of Experimental Medicine 115:503–512
    [Google Scholar]
  13. Henle W., Henle G., Deinhardt F., Bergs V. V. 1959; Studies on persistent infections in tissue cultures. IV. Evidence for the production of an interferon in MCN cells by myxoviruses. Journal of Experimental Medicine 110:525–541
    [Google Scholar]
  14. Henry B. E., Newcomb W. W., O’callaghan D. J. 1979; Biological and biochemical properties of defective interfering particles of equine herpesvirus type 1. Virology 92:495–506
    [Google Scholar]
  15. Henry B. E., Newcomb W. W., O’callaghan D. J. 1980; Alterations in viral protein synthesis and capsid production in infection with DI particles of herpesvirus. Journal of General Virology 47:343–353
    [Google Scholar]
  16. Henry B. E., Robinson R. A., Dauenhauer S. A., Atherton S. S., Hayward G. S., O’callaghan D. J. 1981; Structure of the genome of equine herpesvirus type 1. Virology 115:97–114
    [Google Scholar]
  17. Ho M., Enders J. F. 1959; Further studies on the inhibitor of viral activity appearing in infected cell cultures and its role in chronic viral infections. Virology 9:446–477
    [Google Scholar]
  18. Holland J. J., Villarreal L. P., Welsh R. M., Oldstone M. B. A., Kohne D., Lazzarini R., Scolnick E. 1976; Long-term persistent vesicular stomatitis virus and rabies virus infection of cells in vitro. Journal of General Virology 33:193–211
    [Google Scholar]
  19. Huang A. S. 1973; Defective interfering viruses. Annual Review of Microbiology 27:101–117
    [Google Scholar]
  20. Koprowski H., Ponten J. A., Jensen F., Ravdin R. G., Moorhead P., Saksela E. 1962; Transformation of cultures of human tissues with simian virus 40. Journal of Cellular and Comparative Physiology 59:281–292
    [Google Scholar]
  21. Mocarski E. S., Stinski M. F. 1979; Persistence of the cytomegalovirus genome in human cells. Journal of Virology 31:761–775
    [Google Scholar]
  22. Nishiyama Y. 1977; Studies of L cells persistently infected with VSV: factors involved in the regulation of persistent infection. Journal of General Virology 35:265–279
    [Google Scholar]
  23. O’callaghan D. J., Randall C. C. 1976; Molecular anatomy of herpesviruses: recent studies. Progress in Medical Virology 22:152–210
    [Google Scholar]
  24. O’callaghan D. J., Cheevers W. P., Gentry G. A., Randall C. C. 1968a; Kinetics of cellular and viral DNA synthesis in equine abortion (herpes) virus-infection of L-M cells. Virology 36:104–114
    [Google Scholar]
  25. O’callaghan D. J., Hyde J. M., Gentry G. A., Randall C. C. 1968b; Kinetics of viral deoxyribonucleic acid, protein and infectious particle production and alterations in host macromolecular synthesis in equine abortion (herpes) virus infected cells. Journal of Virology 2:793–804
    [Google Scholar]
  26. O’callaghan D. J., Allen G. P., Randall C. C. 1978; Structure and replication of the equine herpesviruses. In Equine Infectious Diseases vol 4: pp 1–31 Edited by Bryans J., Gerber H. Princeton, New Jersey: Veterinary publications;
    [Google Scholar]
  27. O’callaghan D. J., Henry B. E., Wharton J. H., Dauenhauer S. A., Vance R. B., Staczek J., Atherton S. S., Robinson R. A. 1981; Equine herpesviruses: biochemical studies on genomic structure, DI particles, oncogenic transformation, and persistent infection. In Developments in Molecular Virology I. Herpesvirus DNA pp 387–418 Edited by Becker Y. The Hague: Nijhoff;
    [Google Scholar]
  28. Perdue M. L., Kemp M. C., Randall C. C., O’callaghan D. J. 1974; Studies on the molecular anatomy of L-M cell strain of equine herpesvirus type 1. Proteins of the nucleocapsids and intact virions. Virology 50:201–216
    [Google Scholar]
  29. Perdue M. L., Cohen J. C., Kemp M. C., Randall C. C., O’callaghan D. J. 1975; Characterization of three species of nucleocapsids of equine herpesvirus type 1 (EHV-1). Virology 64:187–205
    [Google Scholar]
  30. Preble O. T., Youngner J. S. 1973a; Temperature-sensitive defect of mutants isolated from L cells persistently infected with Newcastle disease virus. Journal of Virology 12:472–480
    [Google Scholar]
  31. Preble O. T., Youngner J. S. 1973b; Selection of temperature-sensitive mutants during persistent infection: role in maintenance of persistent Newcastle disease virus infections of L cells. Journal of Virology 12:481–491
    [Google Scholar]
  32. Preble O. T., Youngner J. S. 1975; Temperature-sensitive viruses and the etiology of chronic and inapparent infections. Journal of Infectious Diseases 131:467–473
    [Google Scholar]
  33. Rapp F. (editor) 1980 Oncogenic Herpesviruses vol 12: Boca Raton, Florida: CRC Press;
    [Google Scholar]
  34. Reichmann M. E., Schnitzlein W. M. 1979; Defective interfering particles of rhabdoviruses. In Current Topics in Microbiology and Immunology vol 86: pp 123–168 Edited by Arber W., Falkow S., Henle W., Hofschneider P. H., Humphrey J. H., Klein J., Koldovsky P., Koprowski H., Maaloe O., Melchers F., Rott R., Schweiger H. G., Syrucek L., Vogt P. K. Berlin and Heidelberg: Springer-Verlag;
    [Google Scholar]
  35. Robinson R. A., O’callaghan D. J. 1981; The organization of integrated herpesvirus DNA sequences in equine herpesvirus type 1 transformed and tumor cell lines. In Developments in Molecular Virology I. Herpesvirus DNA pp 419–436 Edited by Becker Y. The Hague: Nijhoff;
    [Google Scholar]
  36. Robinson R. A., Henry B. E., Duff R. G., O’callaghan D. J. 1980a; Oncogenic transformation by equine herpesviruses (EHV). I. Properties of hamster embryo cells transformed by ultraviolet-irradiated EHV-1. Virology 101:335–362
    [Google Scholar]
  37. Robinson R. A., Vance R. B., O’callaghan D. J. 1980b; Oncogenic transformation by equine herpesviruses. II. Coestablishment of persistent infection and oncogenic transformation of hamster embryo cells by equine herpesvirus type 1 preparations enriched for defective interfering particles. Journal of Virology 36:204–219
    [Google Scholar]
  38. Robinson R. A., Tucker P. W., Dauenhauer S. A., O’callaghan D. J. 1981; Molecular cloning of equine herpesvirus type 1 DNA: analysis of standard and defective viral genomes and viral sequences in oncogenically transformed cell. Proceedings of the National Academy of Sciences of the United States of America 78:6684–6688
    [Google Scholar]
  39. Roizman B. 1972; The biochemical features of herpesvirus-infected cells, particularly as they relate to their potential oncogenicity-a review. In Oncogenesis and Herpesviruses pp 1–17 Edited by Biggs P. M., de The G., Payne L. N. Lyon, France: International Agency for Research on Cancer;
    [Google Scholar]
  40. Roux L., Holland J. J. 1979; Role of defective interfering particles of Sendai virus in persistent infections. Virology 93:91–103
    [Google Scholar]
  41. Sekellick M. J., Marcus P. I. 1978; Persistent infection. I. Interferon-inducing defective-interfering particles as mediators of cell sparing: possible role in persistent infection by vesicular stomatitis virus. Virology 85:175–186
    [Google Scholar]
  42. Sekellick M. J., Marcus P. I. 1979; Persistent infection. II. Interferon-inducing temperature-sensitive mutants as mediators of cell sparing: possible role in persistent infection by vesicular stomatitis virus. Virology 95:36–47
    [Google Scholar]
  43. Shapiro I. M., Andersson-Anvret M., Klein G. 1978; Poiyploidization of Epstein–Barr virus (EBV)-carrying lymphoma lines decreases the inducibility of EBV-determined early antigen following P3HR-1 virus superinfection or iododeoxyuridine treatment. Intervirology 10:94–101
    [Google Scholar]
  44. Shein H. M., Enders J. F. 1962; Multiplication and cytopathogenicity of simian vacuolating virus 40 in cultures of human tissues. Proceedings of the Society for Experimental Biology and Medicine 109:495–500
    [Google Scholar]
  45. Soehner R. L., Gentry G. A., Randall C. C. 1965; Some physicochemical characteristics of equine abortion virus nucleic acid. Virology 26:395–405
    [Google Scholar]
  46. Spear P. G., Roizman B. 1980; Herpes simplex viruses. In Molecular Biology of Tumor Viruses, part 2: DNA Tumor Viruses pp 615–745 Edited by John Tooze. New York: Cold Spring Harbor Laboratory;
    [Google Scholar]
  47. Stanners C. P., Goldberg V. J. 1975; On the mechanism of neurotropism of vesicular stomatitis virus in newborn hamsters. Studies with temperature-sensitive mutants. Journal of General Virology 29:281–296
    [Google Scholar]
  48. Stevens J. G. 1980; Herpetic latency and reactivation. In Oncogenic Herpesviruses vol 2: pp 1–11 Edited by Fred Rapp. Boca Raton, Florida: CRC Press;
    [Google Scholar]
  49. Stevens J. G., Cook M. 1974; Maintenance of latent herpetic infection: an apparent role for anti-viral IgG. Journal of Immunology 113:1685–1693
    [Google Scholar]
  50. Stollar V. 1979; Defective interfering particles of togaviruses. In Current Topics in Microbiology and Immunology vol 86: pp 35–66 Edited by Arber W., Falkow S., Henle W., Hofschneider P. H., Humphrey J. H., Klein J., Koldovsky P., Koprowski H., Maaloe O., Melchers F., Rott R., Schweiger H. G., Syrucek L., Vogt P. K. Berlin and Heidelberg: Springer-Verlag;
    [Google Scholar]
  51. Wagner R. R. 1974; Pathogenicity and immunogenicity for mice of temperature-sensitive mutants of vesicular stomatitis virus. Infection and Immunity 10:309–315
    [Google Scholar]
  52. Walker D. L. 1964; The viral carrier state in animal cell cultures. Progress in Medical Virology 6:111–148
    [Google Scholar]
  53. Wharton J. H., Henry B. E., O’callaghan D. J. 1981; Equine cytomegalovirus: cultural characteristics and properties of viral DNA. Virology 109:106–119
    [Google Scholar]
  54. Zur Hausen H. 1980; Oncogenic herpesviruses. In Molecular Biology of Tumor Viruses, part 2 DNA Tumor Viruses pp 747–795 Edited by Tooze J. New York: Cold Spring Harbor Laboratory;
    [Google Scholar]
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