1887

Abstract

It has been shown that replication of the Japanese encephalitis virus (JEV) can trigger infected cells to undergo apoptosis. In the present study, it is further demonstrated that replication-incompetent virions of JEV, obtained by short-wavelength ultraviolet (UV) irradiation, could also induce host-cell death. It was found that UV-inactivated JEV (UV-JEV) caused cell death in neuronal cells such as mouse neuroblastoma N18 and human neuronal NT-2 cells, but not in non-neuronal baby hamster kidney BHK-21 fibroblast or human cervical HeLa cells. Only actively growing, but not growth-arrested, cells were susceptible to the cytotoxic effects of UV-JEV. Killing of UV-JEV-infected N18 cells could be antagonized by co-infection with live, infectious JEV, suggesting that virions of UV-JEV might engage an as-yet-unidentified receptor-mediated death-signalling pathway. Characteristically, mitochondrial alterations were evident in UV-JEV-infected N18 cells, as revealed by electron microscopy and a loss of membrane potential. N18 cells infected by UV-JEV induced generation of reactive oxygen species (ROS) as well as the activation of nuclear factor kappa B (NF-B), and the addition of anti-oxidants or specific NF-B inhibitors to the media greatly reduced the cytotoxicity of UV-JEV. Together, the results presented here suggest that replication-incompetent UV-JEV damages actively growing neuronal cells through a ROS-mediated pathway.

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2004-02-01
2019-11-18
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References

  1. Akaike, T., Ando, M., Oda, T., Doi, T., Ijiri, S., Araki, S. & Maeda, H. ( 1990; ). Dependence on O 2 generation by xanthine oxidase of pathogenesis of influenza virus infection in mice. J Clin Invest 85, 739–745.[CrossRef]
    [Google Scholar]
  2. Allan, A. C., Lapidot, M., Culver, J. N. & Fluhr, R. ( 2001; ). An early tobacco mosaic virus-induced oxidative burst in tobacco indicates extracellular perception of the virus coat protein. Plant Physiol 126, 97–108.[CrossRef]
    [Google Scholar]
  3. Amano, T., Richelson, E. & Nirenberg, M. ( 1972; ). Neurotransmitter synthesis by neuroblastoma clones (neuroblast differentiation/cell culture/choline acetyltransferase/acetylcholinesterase/tyrosine hydroxylase/axons-dendrites). Proc Natl Acad Sci U S A 69, 258–263.[CrossRef]
    [Google Scholar]
  4. Baeuerle, P. A. & Baltimore, D. ( 1996; ). NF-kappa B: ten years after. Cell 87, 13–20.[CrossRef]
    [Google Scholar]
  5. Barkett, M. & Gilmore, T. D. ( 1999; ). Control of apoptosis by Rel/NF-kappaB transcription factors. Oncogene 18, 6910–6924.[CrossRef]
    [Google Scholar]
  6. Barton, E. S., Forrest, J. C., Connolly, J. L., Chappell, J. D., Liu, Y., Schnell, F. J., Nusrat, A., Parkos, C. A. & Dermody, T. S. ( 2001; ). Junction adhesion molecule is a receptor for reovirus. Cell 104, 441–451.[CrossRef]
    [Google Scholar]
  7. Baruchel, S. & Wainberg, M. A. ( 1992; ). The role of oxidative stress in disease progression in individuals infected by the human immunodeficiency virus. J Leukoc Biol 52, 111–114.
    [Google Scholar]
  8. Brojatsch, J., Naughton, J., Rolls, M. M., Zingler, K. & Young, J. A. ( 1996; ). CAR1, a TNFR-related protein, is a cellular receptor for cytopathic avian leukosis-sarcoma viruses and mediates apoptosis. Cell 87, 845–855.[CrossRef]
    [Google Scholar]
  9. Burke, D. S. & Monath, T. P. ( 2001; ). Flaviviruses. In Fields Virology, 4th edn, pp. 1043–1125. Edited by D. M. Knipe & P. M. Howley. Philadelphia, PA, USA: Lippincott-Williams & Wilkins.
  10. Carlquist, J. F., Edelman, L., Bennion, D. W. & Anderson, J. L. ( 1999; ). Cytomegalovirus induction of interleukin-6 in lung fibroblasts occurs independently of active infection and involves a G protein and the transcription factor, NF-kappaB. J Infect Dis 179, 1094–1100.[CrossRef]
    [Google Scholar]
  11. Chen, L. K., Liao, C. L., Lin, C. G., Lai, S. C., Liu, C. I., Ma, S. H., Huang, Y. Y. & Lin, Y. L. ( 1996a; ). Persistence of Japanese encephalitis virus is associated with abnormal expression of the nonstructural protein NS1 in host cells. Virology 217, 220–229.[CrossRef]
    [Google Scholar]
  12. Chen, L. K., Lin, Y. L., Liao, C. L., Lin, C. G., Huang, Y. L., Yeh, C. T., Lai, S. C., Jan, J. T. & Chin, C. ( 1996b; ). Generation and characterization of organ-tropism mutants of Japanese encephalitis virus in vivo and in vitro. Virology 223, 79–88.[CrossRef]
    [Google Scholar]
  13. Connolly, J. L., Barton, E. S. & Dermody, T. S. ( 2001; ). Reovirus binding to cell surface sialic acid potentiates virus-induced apoptosis. J Virol 75, 4029–4039.[CrossRef]
    [Google Scholar]
  14. Esser, M. T., Bess, J. W., Jr, Suryanarayana, K., Chertova, E., Marti, D., Carrington, M., Arthur, L. O. & Lifson, J. D. ( 2001; ). Partial activation and induction of apoptosis in CD4(+) and CD8(+) T lymphocytes by conformationally authentic noninfectious human immunodeficiency virus type 1. J Virol 75, 1152–1164.[CrossRef]
    [Google Scholar]
  15. Evan, G. & Littlewood, T. ( 1998; ). A matter of life and cell death. Science 281, 1317–1322.[CrossRef]
    [Google Scholar]
  16. Everett, H. & McFadden, G. ( 2001a; ). Viral proteins and the mitochondrial apoptotic checkpoint. Cytokine Growth Factor Rev 12, 181–188.[CrossRef]
    [Google Scholar]
  17. Everett, H. & McFadden, G. ( 2001b; ). Viruses and apoptosis: meddling with mitochondria. Virology 288, 1–7.[CrossRef]
    [Google Scholar]
  18. Faulkner, K. M., Liochev, S. I. & Fridovich, I. ( 1994; ). Stable Mn(III) porphyrins mimic superoxide dismutase in vitro and substitute for it in vivo. J Biol Chem 269, 23471–23476.
    [Google Scholar]
  19. Ghoshal, K., Majumder, S., Zhu, Q., Hunzeker, J., Datta, J., Shah, M., Sheridan, J. F. & Jacob, S. T. ( 2001; ). Influenza virus infection induces metallothionein gene expression in the mouse liver and lung by overlapping but distinct molecular mechanisms. Mol Cell Biol 21, 8301–8317.[CrossRef]
    [Google Scholar]
  20. Gilgun-Sherki, Y., Melamed, E. & Offen, D. ( 2001; ). Oxidative stress induced-neurodegenerative diseases: the need for antioxidants that penetrate the blood brain barrier. Neuropharmacology 40, 959–975.[CrossRef]
    [Google Scholar]
  21. Green, D. R. & Reed, J. C. ( 1998; ). Mitochondria and apoptosis. Science 281, 1309–1312.[CrossRef]
    [Google Scholar]
  22. Hagen, T. M., Huang, S., Curnutte, J., Fowler, P., Martinez, V., Wehr, C. M., Ames, B. N. & Chisari, F. V. ( 1994; ). Extensive oxidative DNA damage in hepatocytes of transgenic mice with chronic active hepatitis destined to develop hepatocellular carcinoma. Proc Natl Acad Sci U S A 91, 12808–12812.[CrossRef]
    [Google Scholar]
  23. Hanon, E., Meyer, G., Vanderplasschen, A., Dessy-Doize, C., Thiry, E. & Pastoret, P. P. ( 1998; ). Attachment but not penetration of bovine herpesvirus 1 is necessary to induce apoptosis in target cells. J Virol 72, 7638–7641.
    [Google Scholar]
  24. Hatada, E. N., Krappmann, D. & Scheidereit, C. ( 2000; ). NF-kappaB and the innate immune response. Curr Opin Immunol 12, 52–58.[CrossRef]
    [Google Scholar]
  25. Hawkins, C. L. & Davies, M. J. ( 2001; ). Generation and propagation of radical reactions on proteins. Biochim Biophys Acta 1504, 196–219.[CrossRef]
    [Google Scholar]
  26. Israel, N. & Gougerot-Pocidalo, M. A. ( 1997; ). Oxidative stress in human immunodeficiency virus infection. Cell Mol Life Sci 53, 864–870.[CrossRef]
    [Google Scholar]
  27. Jan, J. T., Chen, B. H., Ma, S. H., Liu, C. I., Tsai, H. P., Wu, H. C., Jiang, S. Y., Yang, K. D. & Shaio, M. F. ( 2000; ). Potential dengue virus-triggered apoptotic pathway in human neuroblastoma cells: arachidonic acid, superoxide anion, and NF-kappaB are sequentially involved. J Virol 74, 8680–8691.[CrossRef]
    [Google Scholar]
  28. Kamata, H. & Hirata, H. ( 1999; ). Redox regulation of cellular signalling. Cell Signal 11, 1–14.[CrossRef]
    [Google Scholar]
  29. Karin, M. & Lin, A. ( 2002; ). NF-kappaB at the crossroads of life and death. Nat Immunol 3, 221–227.
    [Google Scholar]
  30. Kesson, A. M. & King, N. J. ( 2001; ). Transcriptional regulation of major histocompatibility complex class I by flavivirus West Nile is dependent on NF-kappaB activation. J Infect Dis 184, 947–954.[CrossRef]
    [Google Scholar]
  31. Kowaltowski, A. J., Castilho, R. F. & Vercesi, A. E. ( 2001; ). Mitochondrial permeability transition and oxidative stress. FEBS Lett 495, 12–15.[CrossRef]
    [Google Scholar]
  32. Kroemer, G. & Reed, J. C. ( 2000; ). Mitochondrial control of cell death. Nat Med 6, 513–519.[CrossRef]
    [Google Scholar]
  33. Kroemer, G., Dallaporta, B. & Resche-Rigon, M. ( 1998; ). The mitochondrial death/life regulator in apoptosis and necrosis. Annu Rev Physiol 60, 619–642.[CrossRef]
    [Google Scholar]
  34. Lallemand, D., Ham, J., Garbay, S., Bakiri, L., Traincard, F., Jeannequin, O., Pfarr, C. M. & Yaniv, M. ( 1998; ). Stress-activated protein kinases are negatively regulated by cell density. EMBO J 17, 5615–5626.[CrossRef]
    [Google Scholar]
  35. Liao, C. L., Lin, Y. L., Wang, J. J., Huang, Y. L., Yeh, C. T., Ma, S. H. & Chen, L. K. ( 1997; ). Effect of enforced expression of human bcl-2 on Japanese encephalitis virus-induced apoptosis in cultured cells. J Virol 71, 5963–5971.
    [Google Scholar]
  36. Liao, C. L., Lin, Y. L., Wu, B. C. & 7 other authors ( 2001; ). Salicylates inhibit flavivirus replication independently of blocking nuclear factor kappa B activation. J Virol 75, 7828–7839.[CrossRef]
    [Google Scholar]
  37. Lin, K. I., Lee, S. H., Narayanan, R., Baraban, J. M., Hardwick, J. M. & Ratan, R. R. ( 1995; ). Thiol agents and Bcl-2 identify an alphavirus-induced apoptotic pathway that requires activation of the transcription factor NF-kappa B. J Cell Biol 131, 1149–1161.[CrossRef]
    [Google Scholar]
  38. Lin, Y. Z., Yao, S. Y., Veach, R. A., Torgerson, T. R. & Hawiger, J. ( 1995; ). Inhibition of nuclear translocation of transcription factor NF-kappa B by a synthetic peptide containing a cell membrane-permeable motif and nuclear localization sequence. J Biol Chem 270, 14255–14258.[CrossRef]
    [Google Scholar]
  39. Lindenbach, B. D. & Rice, C. M. ( 2001; ). Flaviviridae: the viruses and their replication. In Fields Virology, 4th edn, pp. 991–1041. Edited by D. M. Knipe & P. M. Howley. Philadelphia, PA, USA: Lippincott-Williams & Wilkins.
  40. Maher, P. & Schubert, D. ( 2000; ). Signaling by reactive oxygen species in the nervous system. Cell Mol Life Sci 57, 1287–1305.[CrossRef]
    [Google Scholar]
  41. Marianneau, P., Cardona, A., Edelman, L., Deubel, V. & Despres, P. ( 1997; ). Dengue virus replication in human hepatoma cells activates NF-kappaB which in turn induces apoptotic cell death. J Virol 71, 3244–3249.
    [Google Scholar]
  42. Mogensen, T. H. & Paludan, S. R. ( 2001; ). Molecular pathways in virus-induced cytokine production. Microbiol Mol Biol Rev 65, 131–150.[CrossRef]
    [Google Scholar]
  43. Nordberg, J. & Arner, E. S. ( 2001; ). Reactive oxygen species, antioxidants, and the mammalian thioredoxin system. Free Radic Biol Med 31, 1287–1312.[CrossRef]
    [Google Scholar]
  44. Pani, G., Colavitti, R., Bedogni, B., Anzevino, R., Borrello, S. & Galeotti, T. ( 2000; ). A redox signaling mechanism for density-dependent inhibition of cell growth. J Biol Chem 275, 38891–38899.[CrossRef]
    [Google Scholar]
  45. Peterhans, E. ( 1979; ). Sendai virus stimulates chemiluminescence in mouse spleen cells. Biochem Biophys Res Commun 91, 383–392.[CrossRef]
    [Google Scholar]
  46. Ramsey-Ewing, A. & Moss, B. ( 1998; ). Apoptosis induced by a postbinding step of vaccinia virus entry into Chinese hamster ovary cells. Virology 242, 138–149.[CrossRef]
    [Google Scholar]
  47. Raung, S. L., Kuo, M. D., Wang, Y. M. & Chen, C. J. ( 2001; ). Role of reactive oxygen intermediates in Japanese encephalitis virus infection in murine neuroblastoma cells. Neurosci Lett 315, 9–12.[CrossRef]
    [Google Scholar]
  48. Richter, C., Gogvadze, V., Laffranchi, R., Schlapbach, R., Schweizer, M., Suter, M., Walter, P. & Yaffee, M. ( 1995; ). Oxidants in mitochondria: from physiology to diseases. Biochim Biophys Acta 1271, 67–74.[CrossRef]
    [Google Scholar]
  49. Riffault, S., Carrat, C., Milon, G., Charley, B. & Colle, J. H. ( 2000; ). Transient IFN-γ synthesis in the lymph node draining a dermal site loaded with UV-irradiated herpes simplex virus type 1: an NK- and CD3-dependent process regulated by IL-12 but not by IFN-α/β. J Gen Virol 81, 2365–2373.
    [Google Scholar]
  50. Roulston, A., Marcellus, R. C. & Branton, P. E. ( 1999; ). Viruses and apoptosis. Annu Rev Microbiol 53, 577–628.[CrossRef]
    [Google Scholar]
  51. Schwarz, K. B. ( 1996; ). Oxidative stress during viral infection: a review. Free Radic Biol Med 21, 641–649.[CrossRef]
    [Google Scholar]
  52. Sen, C. K. & Packer, L. ( 1996; ). Antioxidant and redox regulation of gene transcription. FASEB J 10, 709–720.
    [Google Scholar]
  53. Speir, E., Shibutani, T., Yu, Z. X., Ferrans, V. & Epstein, S. E. ( 1996; ). Role of reactive oxygen intermediates in cytomegalovirus gene expression and in the response of human smooth muscle cells to viral infection. Circ Res 79, 1143–1152.[CrossRef]
    [Google Scholar]
  54. Stadnyk, A. W., Gillan, T. L. & Anderson, R. ( 1997; ). Respiratory syncytial virus triggers synthesis of IL-6 in BALB/c mouse alveolar macrophages in the absence of virus replication. Cell Immunol 176, 122–126.[CrossRef]
    [Google Scholar]
  55. Su, C. M., Liao, C. L., Lee, Y. L. & Lin, Y. L. ( 2001; ). Highly sulfated forms of heparin sulfate are involved in Japanese encephalitis virus infection. Virology 286, 206–215.[CrossRef]
    [Google Scholar]
  56. Su, H. L., Liao, C. L. & Lin, Y. L. ( 2002; ). Japanese encephalitis virus infection initiates endoplasmic reticulum stress and an unfolded protein response. J Virol 76, 4162–4171.[CrossRef]
    [Google Scholar]
  57. Suzuki, Y. J., Forman, H. J. & Sevanian, A. ( 1997; ). Oxidants as stimulators of signal transduction. Free Radic Biol Med 22, 269–285.[CrossRef]
    [Google Scholar]
  58. Tschopp, J., Thome, M., Hofmann, K. & Meinl, E. ( 1998; ). The fight of viruses against apoptosis. Curr Opin Genet Dev 8, 82–87.[CrossRef]
    [Google Scholar]
  59. Tyler, K. L., Squier, M. K., Rodgers, S. E., Schneider, B. E., Oberhaus, S. M., Grdina, T. A., Cohen, J. J. & Dermody, T. S. ( 1995; ). Differences in the capacity of reovirus strains to induce apoptosis are determined by the viral attachment protein sigma 1. J Virol 69, 6972–6979.
    [Google Scholar]
  60. Yu, B. P. ( 1994; ). Cellular defenses against damage from reactive oxygen species. Physiol Rev 74, 139–162.
    [Google Scholar]
  61. Yurochko, A. D., Hwang, E. S., Rasmussen, L., Keay, S., Pereira, L. & Huang, E. S. ( 1997; ). The human cytomegalovirus UL55 (gB) and UL75 (gH) glycoprotein ligands initiate the rapid activation of Sp1 and NF-kappaB during infection. J Virol 71, 5051–5059.
    [Google Scholar]
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