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Conversion of lytic to persistent alphavirus infection by the bcl-2 cellular oncogene

Nature volume 361, pages 739–742 (1993)Cite this article

Abstract

LITTLE is known about virus–host cell interactions that regulate the lytic potential of viruses during productive replication. Sindbis virus (SV), a single-stranded positive-sense RNA virus in the alphavirus genus (family Togaviridae), results in lytic infection in most vertebrate cell lines, but persistent productive infection in post-mitotic neurons1. The cellular oncogene bcl-2, which encodes an inner mitochondrial membrane protein of Mr 26,000 (ref. 2), blocks programmed cell death (apoptosis) in neurons3. We therefore investigated whether SV infection induces programmed cell death in non-neuronal cells, and if so, whether virus-induced programmed cell death can be blocked by transfection with bcl-2. We demonstrate that SV infection of baby hamster kidney (BHK-2), mouse neuroblastoma (N18), and rat prostatic adenocarcinoma (AT-3) cells results in programmed cell death, whereas SV infection of bcl-2-transfected AT-3 cells results in long-term persistent productive infection. Thus cellular bcl-2 oncogene expression plays a role in the establishment of persistent viral infection by blocking virus-induced programmed cell death.

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References

  1. Levine, B. et al. Science 254, 856–860 (1991).

    Article  ADS  CAS  Google Scholar 

  2. Hockenbery, D., Nunez, G., Milliman, C., Schreiber, R. D. & Korsmeyer, S. J. Nature 348, 334–336 (1990).

    Article  ADS  CAS  Google Scholar 

  3. Garcia, I., Martinou, I., Tsujimoto, Y. & Martinou, J. C. Science 258, 302–304 (1992).

    Article  ADS  CAS  Google Scholar 

  4. Terai, C., Kornbluth, R. S., Pauza, C. D., Richman, D. D. & Carson, D. A. J. clin. Invest. 87, 1710–1715 (1991).

    Article  CAS  Google Scholar 

  5. Laurent-Crawford, A. G. et al. Virology 185, 829–839 (1991).

    Article  CAS  Google Scholar 

  6. Rao, L. et al. Proc. natn. Acad. Sci. U.S.A. 89, 7742–7746 (1992).

    Article  ADS  CAS  Google Scholar 

  7. Wylie, A. H., Kerr, J. F. R. & Curie, A. R. Int. Rev. Cytol. 68, 251–306 (1980).

    Article  Google Scholar 

  8. Arends, M. J. & Wylie, A. H. Int. Rev. exp. Path. 32, 223–254 (1991).

    Article  CAS  Google Scholar 

  9. Johnson, R. T., McFarland, H. F. & Levy, S. E. J. infect. Dis. 125, 257–262 (1972).

    Article  CAS  Google Scholar 

  10. Martin, D. P. & Johnson, E. M. Jr in Apoptosis: The Molecular Basis of Cell Death (eds Tomei, L. D. & Cope, F. O.) 247–261 (Cold Spring Harbor Laboratory Press, New York, 1991).

    Google Scholar 

  11. Server, A. C. & Mobley, W. C. in Apoptosis: The Molecular Basis of Cell Death (eds Tomei, L. D. & Cope, F. O.) 263–278 (Cold Spring Harbor Laboratory Press, New York, 1991).

    Google Scholar 

  12. Negrini, M., Silini, E., Kozak, C., Tsujimoto, Y. & Croce, C. M. Cell 49, 455–463 (1987).

    Article  CAS  Google Scholar 

  13. Hockenbery, D. M., Zutter, M., Hickey, W., Nahm, M. & Korsmeyer, S. J. Proc. natn. Acad. Sci. U.S.A. 88, 6961–6965 (1991).

    Article  ADS  CAS  Google Scholar 

  14. Froshauer, S., Kartenbeck, A. & Helenius, A. J. Cell Biol. 107, 2075–2086 (1988).

    Article  CAS  Google Scholar 

  15. Buchmeier, M. J., Welsh, R. M., Dutko, F. J. & Oldstone, M. B. A. Adv. Immun. 30, 275–331 (1980).

    Article  CAS  Google Scholar 

  16. Clem, R. J., Fechmeimer, M. & Miller, L. K. Science 254, 1388–1390 (1991).

    Article  ADS  CAS  Google Scholar 

  17. Henderson, S. et al. Cell 65, 1107–1115 (1991).

    Article  CAS  Google Scholar 

  18. Gregory, C. D. et al. Nature 349, 612–614 (1991).

    Article  ADS  CAS  Google Scholar 

  19. Chou, J. & Roizman, B. Proc. natn. Acad. Sci. U.S.A. 89, 3266–3270 (1992).

    Article  ADS  CAS  Google Scholar 

  20. Nunez, G. et al. J. Immun. 144, 3602–3610 (1990).

    CAS  Google Scholar 

  21. Martikainen, P., Kyprianou, N., Tucker, R. W. & Isaacs, J. T. Cancer Res. 51, 4693–4700 (1991).

    CAS  PubMed  Google Scholar 

  22. Sorensen, C. M., Barry, M. A. & Eastman, A. J. natn. Cancer Inst. 82, 749–755 (1990).

    Article  Google Scholar 

  23. Tsujimoto, Y. & Croce, C. Proc. natn. Acad. Sci. U.S.A. 83, 5214–5218 (1986).

    Article  ADS  CAS  Google Scholar 

  24. Levine, B. & Griffin, D. E. J. Virol. 66, 6429–6435 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Reed, J. C., Cuddy, M., Slabiak, T., Croce, C. M. & Nowell, P. C. Nature 336, 259–261 (1988).

    Article  ADS  CAS  Google Scholar 

  26. Cepko, C., Roberts, B. & Mulligan, R. Cell 37, 1063–1062 (1984).

    Article  Google Scholar 

  27. Trieger, B. & Isaacs, J. J. Urol. 140, 1580–1586 (1988)

    Article  Google Scholar 

  28. Reed, J. C. et al. Cancer Res. 51, 6529–6538 (1991).

    CAS  PubMed  Google Scholar 

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Author notes

  1. Beth Levine

    Present address: Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, 10032, USA

Authors and Affiliations

  1. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21287-7681, USA

    Beth Levine & Diane E. Griffin

  2. Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21287-7681, USA

    Qi Huang & J. Marie Hardwick

  3. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21287-7681, USA

    John T. Isaacs

  4. Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21287-7681, USA

    John T. Isaacs

  5. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21287-7681, USA

    Diane E. Griffin & J. Marie Hardwick

  6. La Jolla Cancer Research Foundation, Cancer Research Institute, La Jolla, California, 92037, USA

    John C. Reed

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  1. Beth Levine
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  2. Qi Huang
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  3. John T. Isaacs
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  4. John C. Reed
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  5. Diane E. Griffin
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  6. J. Marie Hardwick
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Levine, B., Huang, Q., Isaacs, J. et al. Conversion of lytic to persistent alphavirus infection by the bcl-2 cellular oncogene. Nature 361, 739–742 (1993). https://doi.org/10.1038/361739a0

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