1887

Abstract

The induction of apoptotic cell death is a prominent cytopathic effect of dengue (DEN) viruses. One of the key questions to be addressed is which viral components induce apoptosis in DEN virus-infected cells. This study investigated whether the small membrane (M) protein was involved in the induction of apoptosis by DEN virus. This was addressed by using a series of enhanced green fluorescent protein-fused DEN proteins. Evidence is provided that intracellular production of the M ectodomains (residues M-1 to M-40) of all four DEN serotypes triggered apoptosis in host cells such as mouse neuroblastoma Neuro 2a and human hepatoma HepG2 cells. The M ectodomains of the wild-type strains of Japanese encephalitis, West Nile and yellow fever viruses also had proapoptotic properties. The export of the M ectodomain from the Golgi apparatus to the plasma membrane appeared to be essential for the initiation of apoptosis. The study found that anti-apoptosis protein Bcl-2 protected HepG2 cells against the death-promoting activity of the DEN M ectodomain. This suggests that the M ectodomain exerts its cytotoxic effects by activating a mitochondrial apoptotic pathway. The cytotoxicity of the DEN M ectodomain reflected the intrinsic proapoptotic properties of the nine carboxy-terminal amino acids (residues M-32 to M-40) designated . Residue M-36 was unique in that it modulated the death-promoting activity of the M ectodomain. Defining the -activated signalling pathways leading to apoptosis will provide the basis for studying how the M protein might play a key role in the fate of the flavivirus-infected cells.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.19163-0
2003-10-01
2019-12-05
Loading full text...

Full text loading...

/deliver/fulltext/jgv/84/10/vir842781.html?itemId=/content/journal/jgv/10.1099/vir.0.19163-0&mimeType=html&fmt=ahah

References

  1. Adams, J. M. & Cory, S. ( 2001; ). Life-or-death decisions by the Bcl-2 protein family. Trends Biochem Sci 26, 61–66.[CrossRef]
    [Google Scholar]
  2. Bray, M. & Lai, C.-J. ( 1991; ). Dengue virus premembrane and membrane proteins elicit a protective immune response. Virology 185, 505–508.[CrossRef]
    [Google Scholar]
  3. Burns, T. F. & El-Deiry, W. S. ( 1999; ). The p53 pathway and apoptosis. J Cell Physiol 181, 231–239.[CrossRef]
    [Google Scholar]
  4. Catteau, A., Courageot, M.-P. & Desprès, P. ( 2003; ). Flaviviruses and apoptosis regulation. In Viruses and Apoptosis. Progress in Molecular and Subcellular Biology. Edited by C. Alonso. Heidelberg: Springer.
  5. Chambers, T. J., Hahn, C. S., Galler, R. & Rice, C. M. ( 1990; ). Flavivirus genome organization, expression and replication. Annu Rev Microbiol 44, 649–688.[CrossRef]
    [Google Scholar]
  6. Cocquerel, L., Duvet, S., Meunier, J.-C., Pillez, A., Cacan, R., Wychowski, C. & Dubuisson, J. ( 1999; ). The transmembrane domain of hepatitis C virus glycoprotein E1 is a signal for static retention in the endoplasmic reticulum. J Virol 73, 2641–2649.
    [Google Scholar]
  7. Courageot, M.-P., Catteau, A. & Desprès, P. ( 2003; ). Mechanisms of virus-induced cell death. In The Flaviviruses: Current Molecular Aspects of Evolution, Biology and Disease Prevention. Edited by T. J. Chambers & T. P. Monath. New York: Academic Press.
  8. Desagher, S. & Martinou, J.-C. ( 2000; ). Mitochondria as the central control point of apoptosis. Trends Cell Biol 10, 369–377.[CrossRef]
    [Google Scholar]
  9. Desprès, P., Cahour, A., Dupuy, A., Deubel, V., Bouloy, M., Digoutte, J.-P. & Girard, M. ( 1987; ). High genetic stability of the region coding for the structural proteins of yellow fever virus strain 17D. J Gen Virol 68, 2245–2247.[CrossRef]
    [Google Scholar]
  10. Desprès, P., Frenkiel, M.-P. & Deubel, V. ( 1993; ). Differences between cell membrane fusion activities of two dengue type-1 isolates reflect modifications of viral structure. Virology 196, 209–219.[CrossRef]
    [Google Scholar]
  11. Desprès, P., Flamand, M., Ceccaldi, P.-E. & Deubel, V. ( 1996; ). Human isolates of dengue type-1 virus induce apoptosis in mouse neuroblastoma cells. J Virol 70, 4090–4096.
    [Google Scholar]
  12. Desprès, P., Frenkiel, M.-P., Ceccaldi, P.-E., Duarte dos Santos, C. & Deubel, V. ( 1998; ). Apoptosis in the mouse central nervous system in response to infection with mouse-neurovirulent dengue viruses. J Virol 72, 823–829.
    [Google Scholar]
  13. Duarte dos Santos, C. N., Frenkiel, M.-P., Courageot, M.-P., Rocha, C. F. S., Vazeille-Falcoz, M.-C., Wien, M. W., Rey, F. A., Deubel, V. & Desprès, P. ( 2000; ). Determinants in the envelope E protein and viral RNA helicase NS3 that influence the induction of apoptosis in response to infection with dengue type-1 virus. Virology 274, 292–308.[CrossRef]
    [Google Scholar]
  14. Fearnhead, H. O., McCurrach, M. E., O'Neill, J., Zhang, K., Lowe, S. W. & Lazebnik, Y. A. ( 1997; ). Oncongene-dependent apoptosis in extracts from drug-resistant cells. Genes Dev 11, 1266–1276.[CrossRef]
    [Google Scholar]
  15. Ferri, K. F. & Kroemer, G. ( 2001; ). Organelle-specific initiation of cell death pathways. Nature Cell Biol 3, 255–263.[CrossRef]
    [Google Scholar]
  16. Gluzman, Y. ( 1981; ). SV40-transformed simian cells support the replication of early SV40 mutants. Cell 23, 175–182.[CrossRef]
    [Google Scholar]
  17. Grabenhorst, E. & Conradt, H. S. ( 1999; ). The cytoplasmic, transmembrane and stem regions of glycosyltransferases specify their in vivo functional sublocalization and stability in the Golgi. J Biol Chem 274, 36107–36116.[CrossRef]
    [Google Scholar]
  18. Hahn, C. S., Dalrymple, J. M., Strauss, J. H. & Rice, C. R. ( 1987; ). Comparison of the virulent Asibi strain of yellow fever virus with the 17D vaccine strain derived from it. Proc Natl Acad Sci U S A 84, 2019–2023.[CrossRef]
    [Google Scholar]
  19. Hengartner, M. O. ( 2000; ). The biochemistry of apoptosis. Nature 407, 770–776.[CrossRef]
    [Google Scholar]
  20. 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-κB are sequentially involved. J Virol 74, 8680–8691.[CrossRef]
    [Google Scholar]
  21. Jürgensmeier, J. M., Xie, Z., Deveraux, Q., Ellerby, L., Bredesen, D. & Reed, J. C. ( 1998; ). Bax directly induces release of cytochrome c from isolated mitochondria. Proc Natl Acad Sci U S A 95, 4997–5002.[CrossRef]
    [Google Scholar]
  22. Kimura, K., Sasano, H., Shimosegawa, T., Mochizuki, S., Nagura, H. & Toyota, T. ( 2000; ). Ultrastructure of cells undergoing apoptosis. Vitam Horm 58, 257–266.
    [Google Scholar]
  23. Kuhn, R. J., Zhang, W., Rossman, M. G. & 9 other authors ( 2002; ). Structure of dengue virus: implications for flavivirus organization, maturation and fusion. Cell 108, 717–725.[CrossRef]
    [Google Scholar]
  24. Kuwana, T., Mackey, M. R., Perkins, G., Ellisman, M. H., Latterich, M., Schneiter, R., Green, D. R. & Newmeyer, D. D. ( 2002; ). Bid, Bax and lipids cooperate to form supramolecular openings in the outer mitochondrial membrane. Cell 111, 331–342.[CrossRef]
    [Google Scholar]
  25. 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]
  26. Liao, C.-J., Lin, Y.-L., Shen, S.-C. & 7 other authors ( 1998; ). Antiapoptotic but not antiviral function of human bcl-2 assists establishment of Japanese encephalitis virus persistence in cultured cells. J Virol 72, 9844–9854.
    [Google Scholar]
  27. Lin, Y.-L., Liu, C.-C., Lei, H.-Y., Yeh, T.-M., Lin, Y.-S., Chen, R. M.-Y. & Liu, H.-S. ( 2000; ). Infection of five human liver cell lines by dengue-2 virus. J Med Virol 60, 425–431.[CrossRef]
    [Google Scholar]
  28. Lomonosova, E., Subramanian, T. & Chinnadurai, G. ( 2002; ). Requirement of BAX for efficient adenovirus-induced apoptosis. J Virol 76, 11283–11290.[CrossRef]
    [Google Scholar]
  29. Louis, N., Evelegh, C. & Graham, F. L. ( 1997; ). Cloning and sequencing of the cellular–viral junctions from the human adenovirus type 5 transformed 293 cell line. Virology 233, 423–429.[CrossRef]
    [Google Scholar]
  30. Marianneau, P., Cardona, A., Edelman, L., Deubel, V. & Desprès, P. ( 1997; ). Dengue virus replication in human hepatoma cells activates NF-κB which in turn induces apoptotic cell death. J Virol 71, 3244–3249.
    [Google Scholar]
  31. Marianneau, P., Steffan, A.-M., Royer, C., Drouet, M.-T., Kirn, A. & Deubel, V. ( 1998; ). Differing infection patterns of dengue and yellow fever viruses in a human hepatoma cell line. J Infect Dis 178, 1270–1278.[CrossRef]
    [Google Scholar]
  32. Monath, T. P. ( 1999; ). Yellow fever virus (Flaviviridae). In Encyclopedia of Virology, 2nd edn, pp. 1979–1986. Edited by A. Granoff & R. G. Webster. New York: Academic Press.
  33. Parquet, M. D. C., Kumatori, A., Hasebe, F., Morita, K. & Igarashi, A. ( 2001; ). West Nile virus-induced bax-dependent apoptosis. FEBS Lett 500, 17–24.[CrossRef]
    [Google Scholar]
  34. Parquet, M. C., Kumatori, A., Hasebe, F., Mathenge, E. G. M. & Morita, K. ( 2002; ). St Louis encephalitis virus induced pathology in cultured cells. Arch Virol 147, 1105–1119.[CrossRef]
    [Google Scholar]
  35. Pelham, H. R. ( 1996; ). The dynamic organisation of the secretory pathway. Cell Struct Funct 21, 413–419.[CrossRef]
    [Google Scholar]
  36. Prikhod'ko, G. G., Prikhod'ko, E. A., Cohen, J. I. & Pletnev, A. G. ( 2001; ). Infection with Langat flavivirus or expression of the envelope protein induces apoptotic cell death. Virology 286, 328–335.[CrossRef]
    [Google Scholar]
  37. Prikhod'ko, G. G., Prikhod'ko, E. A., Pletnev, A. G. & Cohen, J. I. ( 2002; ). Langat flavivirus protease NS3 binds caspase-8 and induces apoptosis. J Virol 76, 5701–5710.[CrossRef]
    [Google Scholar]
  38. Rice, C. M. ( 1996; ). Flaviviridae: the viruses and their replication. In Fields Virology, 3rd edn, pp. 931–959. Edited by B. N. Fields, D. M. Knipe & P. M. Howley. Philadelphia: Lippincott–Raven.
  39. Su, H.-L., Lin, Y.-L., Yu, H.-P., Tsao, C.-H., Chen, L.-K., Liu, Y.-T. & Liao, C.-L. ( 2001; ). The effect of human bcl-2 and bcl-X genes on dengue virus-induced apoptosis in cultured cells. Virology 282, 141–153.[CrossRef]
    [Google Scholar]
  40. 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]
  41. Tsai, S.-C., Pasumarthi, K. B. S., Pajak, L., Franklin, M., Patton, B., Wang, H., Henzel, W. J., Stults, J. T. & Field, L. J. ( 2000; ). Simian virus 40 large T antigen binds a novel Bcl-2 homology domain 3-containing proapoptosis protein in the cytoplasm. J Biol Chem 275, 3239–3246.[CrossRef]
    [Google Scholar]
  42. Vazquez, S., Guzman, M. G., Guillen, G. & 9 other authors ( 2002; ). Immune response to synthetic peptides of dengue prM protein. Vaccine 20, 1823–1830.[CrossRef]
    [Google Scholar]
  43. Wang, E., Ryman, K. D., Jennings, A. D., Wood, D. J., Taffs, F., Minor, P. D., Sanders, P. G. & Barrett, A. D. T. ( 1995; ). Comparison of the genomes of the wild-type French viscerotropic strain of yellow fever virus with its vaccine derivative French neurotropic vaccine. J Gen Virol 76, 2749–2755.[CrossRef]
    [Google Scholar]
  44. White, E. ( 2001; ). Regulation of the cell cycle and apoptosis by the oncogenes of adenovirus. Oncogene 20, 7836–7846.[CrossRef]
    [Google Scholar]
  45. Xiao, S.-Y., Zhang, H., Guzman, H. & Tesh, R. B. ( 2001; ). Experimental yellow fever virus infection in the golden hamster (Mesocricetus auratus). II. Pathology. J Infect Dis 183, 1437–1444.[CrossRef]
    [Google Scholar]
  46. Yang, J., Liu, X., Bhalla, K., Kim, C. N., Ibrado, A. M., Cai, J., Peng, T. I., Jones, D. P. & Wang, X. ( 1997; ). Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science 275, 1129–1132.[CrossRef]
    [Google Scholar]
  47. Ying, H., Nakayama, E., Robinson, W. H. & Parnes, J. R. ( 1995; ). Structure of the mouse CD72 (Lyb-2) gene and its alternatively spliced transcripts. J Immunol 154, 2743–2752.
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.19163-0
Loading
/content/journal/jgv/10.1099/vir.0.19163-0
Loading

Data & Media loading...

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error