This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jan, J.-T.
Right arrow Articles by Shaio, M.-F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jan, J.-T.
Right arrow Articles by Shaio, M.-F.

 Previous Article  |  Next Article 

Journal of Virology, September 2000, p. 8680-8691, Vol. 74, No. 18
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Potential Dengue Virus-Triggered Apoptotic Pathway in Human Neuroblastoma Cells: Arachidonic Acid, Superoxide Anion, and NF-kappa B Are Sequentially Involved

Jia-Tsrong Jan,1,2 Bor-Horng Chen,3 Shiou-Hwa Ma,1 Chiu-I Liu,1 Hui-Ping Tsai,1 Han-Chung Wu,1 Shian-Yuan Jiang,1,2 Kuen-Der Yang,4 and Men-Fang Shaio1,3,*

Institute of Preventive Medicine,1 Department of Microbiology and Immunology,2 and Department of Tropical Medicine and Parasitology,3 National Defense Medical Center, Taipei, and Chang Gung Children's Hospital, Chang Gung University, Kaohsiung,4 Taiwan, Republic of China

Received 4 February 2000/Accepted 20 June 2000

Direct in vivo evidence for the susceptibility of human neuronal cells to dengue virus has not been reported. In this study, we demonstrated that type 2 dengue (DEN-2) virus infection induced extensive apoptosis in the human neuroblastoma cell line SK-N-SH. Phospholipase A2 (PLA2) was activated by DEN-2 infection, which led to the generation of arachidonic acid (AA). Inhibition of PLA2 activity by the PLA2 inhibitors, AACOCF3 and ONO-RS-082, diminished DEN-2 virus-induced apoptosis. In contrast, the cyclooxygenase inhibitors aspirin and indomethacin, thought to increase AA accumulation by blocking AA catabolism, enhanced apoptosis. Exogenous AA induced apoptosis in a dose-dependent manner. Superoxide anion, which is thought to be generated through the AA-activated NADPH oxidase, was increased after infection. Pretreatment with superoxide dismutase (SOD) protected cells against DEN-2 virus-induced apoptosis. Furthermore, generation of superoxide anion was blocked by AACOCF3. In addition, the transcription factors, NF-kappa B and c-Jun, were found to be activated after DEN-2 virus infection. However, pretreatment of cells with oligodeoxynucleotides containing NF-kappa B, but not c-Jun, binding sites (transcription factor decoy) strongly prevented dengue virus-induced apoptosis. The finding that AACOCF3 and SOD significantly block activation of NF-kappa B suggests that this activation is derived from the AA-superoxide anion pathway. Our results indicate that DEN-2 virus infection of human neuroblastoma cells triggers an apoptotic pathway through PLA2 activation to superoxide anion generation and subsequently to NF-kappa B activation. This apoptotic effect can be either directly derived from the action of AA and superoxide anion on mitochondria or indirectly derived from the products of apoptosis-related genes activated by NF-kappa B.

* Corresponding author. Mailing address: Institute of Preventive Medicine, National Defense Medical Center, P.O. Box 90048-700, Taipei, Taiwan, Republic of China. Phone: (886)-2-2671-1001. Fax: (886)-2-2673-1154. E-mail: p1000141{at}tpts4.seed.net.tw.

Journal of Virology, September 2000, p. 8680-8691, Vol. 74, No. 18
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Brown, M. G., Huang, Y. Y., Marshall, J. S., King, C. A., Hoskin, D. W., Anderson, R. (2009). Dramatic caspase-dependent apoptosis in antibody-enhanced dengue virus infection of human mast cells. J. Leukoc. Biol. 85: 71-80 [Abstract] [Full Text]  
  • Yen, Y.-T., Chen, H.-C., Lin, Y.-D., Shieh, C.-C., Wu-Hsieh, B. A. (2008). Enhancement by Tumor Necrosis Factor Alpha of Dengue Virus-Induced Endothelial Cell Production of Reactive Nitrogen and Oxygen Species Is Key to Hemorrhage Development. J. Virol. 82: 12312-12324 [Abstract] [Full Text]  
  • Samuel, M. A., Morrey, J. D., Diamond, M. S. (2007). Caspase 3-Dependent Cell Death of Neurons Contributes to the Pathogenesis of West Nile Virus Encephalitis. J. Virol. 81: 2614-2623 [Abstract] [Full Text]  
  • Furst, R., Blumenthal, S. B., Kiemer, A. K., Zahler, S., Vollmar, A. M. (2006). Nuclear Factor-{kappa}B-Independent Anti-Inflammatory Action of Salicylate in Human Endothelial Cells: Induction of Heme Oxygenase-1 by the c-Jun N-Terminal Kinase/Activator Protein-1 Pathway. J. Pharmacol. Exp. Ther. 318: 389-394 [Abstract] [Full Text]  
  • Liu, M., Vakharia, V. N. (2006). Nonstructural protein of infectious bursal disease virus inhibits apoptosis at the early stage of virus infection.. J. Virol. 80: 3369-3377 [Abstract] [Full Text]  
  • Kirschnek, S., Gulbins, E. (2006). Phospholipase A2 Functions in Pseudomonas aeruginosa- Induced Apoptosis. Infect. Immun. 74: 850-860 [Abstract] [Full Text]  
  • Lee, C.-J., Liao, C.-L., Lin, Y.-L. (2005). Flavivirus Activates Phosphatidylinositol 3-Kinase Signaling To Block Caspase-Dependent Apoptotic Cell Death at the Early Stage of Virus Infection. J. Virol. 79: 8388-8399 [Abstract] [Full Text]  
  • Reyes-del Valle, J., Chavez-Salinas, S., Medina, F., del Angel, R. M. (2005). Heat Shock Protein 90 and Heat Shock Protein 70 Are Components of Dengue Virus Receptor Complex in Human Cells. J. Virol. 79: 4557-4567 [Abstract] [Full Text]  
  • Matsuda, T., Almasan, A., Tomita, M., Tamaki, K., Saito, M., Tadano, M., Yagita, H., Ohta, T., Mori, N. (2005). Dengue virus-induced apoptosis in hepatic cells is partly mediated by Apo2 ligand/tumour necrosis factor-related apoptosis-inducing ligand. J. Gen. Virol. 86: 1055-1065 [Abstract] [Full Text]  
  • Lin, C.-F., Chiu, S.-C., Hsiao, Y.-L., Wan, S.-W., Lei, H.-Y., Shiau, A.-L., Liu, H.-S., Yeh, T.-M., Chen, S.-H., Liu, C.-C., Lin, Y.-S. (2005). Expression of Cytokine, Chemokine, and Adhesion Molecules during Endothelial Cell Activation Induced by Antibodies against Dengue Virus Nonstructural Protein 1. J. Immunol. 174: 395-403 [Abstract] [Full Text]  
  • Guirakhoo, F., Pugachev, K., Zhang, Z., Myers, G., Levenbook, I., Draper, K., Lang, J., Ocran, S., Mitchell, F., Parsons, M., Brown, N., Brandler, S., Fournier, C., Barrere, B., Rizvi, F., Travassos, A., Nichols, R., Trent, D., Monath, T. (2004). Safety and Efficacy of Chimeric Yellow Fever-Dengue Virus Tetravalent Vaccine Formulations in Nonhuman Primates. J. Virol. 78: 4761-4775 [Abstract] [Full Text]  
  • Lin, R.-J., Liao, C.-L., Lin, Y.-L. (2004). Replication-incompetent virions of Japanese encephalitis virus trigger neuronal cell death by oxidative stress in a culture system. J. Gen. Virol. 85: 521-533 [Abstract] [Full Text]  
  • Catteau, A., Kalinina, O., Wagner, M.-C., Deubel, V., Courageot, M.-P., Despres, P. (2003). Dengue virus M protein contains a proapoptotic sequence referred to as ApoptoM. J. Gen. Virol. 84: 2781-2793 [Abstract] [Full Text]  
  • Clarke, P., Meintzer, S. M., Moffitt, L. A., Tyler, K. L. (2003). Two Distinct Phases of Virus-induced Nuclear Factor kappa B Regulation Enhance Tumor Necrosis Factor-related Apoptosis-inducing Ligand-mediated Apoptosis in Virus-infected Cells. J. Biol. Chem. 278: 18092-18100 [Abstract] [Full Text]  
  • Wang, S.-H., Syu, W.-J., Huang, K.-J., Lei, H.-Y., Yao, C.-W., King, C.-C., Hu, S.-T. (2002). Intracellular localization and determination of a nuclear localization signal of the core protein of dengue virus. J. Gen. Virol. 83: 3093-3102 [Abstract] [Full Text]  
  • Chen, C.-J., Raung, S.-L., Kuo, M.-D., Wang, Y.-M. (2002). Suppression of Japanese encephalitis virus infection by non-steroidal anti-inflammatory drugs. J. Gen. Virol. 83: 1897-1905 [Abstract] [Full Text]  
  • Lin, C.-F., Lei, H.-Y., Shiau, A.-L., Liu, H.-S., Yeh, T.-M., Chen, S.-H., Liu, C.-C., Chiu, S.-C., Lin, Y.-S. (2002). Endothelial Cell Apoptosis Induced by Antibodies Against Dengue Virus Nonstructural Protein 1 Via Production of Nitric Oxide. J. Immunol. 169: 657-664 [Abstract] [Full Text]  
  • Liao, C.-L., Lin, Y.-L., Wu, B.-C., Tsao, C.-H., Wang, M.-C., Liu, C.-I, Huang, Y.-L., Chen, J.-H., Wang, J.-P., Chen, L.-K. (2001). Salicylates Inhibit Flavivirus Replication Independently of Blocking Nuclear Factor Kappa B Activation. J. Virol. 75: 7828-7839 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»