1887

Abstract

Tumor necrosis factor alpha (TNF-) has an antiviral role in some infections but in dengue virus (DENV) infection it is linked to severe pathology. We have previously shown that TNF- stimulation cannot activate nuclear factor B (NF-B) to the fullest extent in DENV-2-infected cells. Here, we investigate further responses of DENV-2-infected cells to TNF-, focussing particularly on cell death and pro-survival signals. TNF- stimulation of productively DENV-2-infected monocyte-derived macrophages or HEK-293 cells induced caspase-3-mediated cell death. While TNF- induced comparable degradation of the inhibitor of NF-B alpha (IB-) and NF-B activation in mock-infected and DENV-2-infected cells early in infection, later in infection and coinciding with TNF--induced cell death, TNF--stimulated IB- degradation and NF-B activation was reduced. This was associated with reduced levels of sphingosine kinase-1 (SphK1) activity in DENV-2-infected cells; SphK1 being a known mediator of TNF--stimulated survival signals. Transfection experiments demonstrated inhibition of TNF--stimulated NF-B activation by expression of DENV-2 capsid (CA) but enhancement by DENV-2 NS5 protein. DENV-2 CA alone, however, did not induce TNF--stimulated cell death or inhibit SphK1 activity. Thus, productively DENV-2-infected cells have compromised TNF--stimulated survival pathways and show enhanced susceptibility to TNF--stimulated cell death, suggesting a role for TNF- in the killing of healthy productively DENV-2-infected cells. Additionally, the altered ability of TNF- to activate NF-B as infection progresses is reflected by the opposing actions of DENV-2 CA and NS5 proteins on TNF--stimulated NF-B activation and could have important consequences for NF-B-driven release of inflammatory cytokines.

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2011-04-01
2019-11-22
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References

  1. Alvarez, S. E., Harikumar, K. B., Hait, N. C., Allegood, J., Strub, G. M., Kim, E. Y., Maceyka, M., Jiang, H., Luo, C. & other authors ( 2010; ). Sphingosine-1-phosphate is a missing cofactor for the E3 ubiquitin ligase TRAF2. Nature 465, 1084–1088.[CrossRef]
    [Google Scholar]
  2. Atrasheuskaya, A., Petzelbauer, P., Fredeking, T. M. & Ignatyev, G. ( 2003; ). Anti-TNF antibody treatment reduces mortality in experimental dengue virus infection. FEMS Immunol Med Microbiol 35, 33–42. [CrossRef]
    [Google Scholar]
  3. Bulich, R. & Aaskov, J. G. ( 1992; ). Nuclear localization of dengue 2 virus core protein detected with monoclonal antibodies. J Gen Virol 73, 2999–3003.[CrossRef]
    [Google Scholar]
  4. Carr, J. M., Hocking, H., Bunting, K., Wright, P. J., Davidson, A., Gamble, J., Burrell, C. J. & Li, P. ( 2003; ). Supernatants from dengue virus type-2 infected macrophages induce permeability changes in endothelial cell monolayers. J Med Virol 69, 521–528. [CrossRef]
    [Google Scholar]
  5. Catteau, A., Kalinina, O., Wagner, M. C., Deubel, V., Courageot, M. P. & Desprès, P. ( 2003; ). Dengue virus M protein contains a proapoptotic sequence referred to as ApoptoM. J Gen Virol 84, 2781–2793. [CrossRef]
    [Google Scholar]
  6. Chen, G. & Goeddel, D. V. ( 2002; ). TNF-R1 signaling: a beautiful pathway. Science 296, 1634–1635.[CrossRef]
    [Google Scholar]
  7. Chen, Y. C. & Wang, S. Y. ( 2002; ). Activation of terminally differentiated human monocytes/macrophages by dengue virus: productive infection, hierarchical production of innate cytokines and chemokines, and the synergistic effect of lipopolysaccharide. J Virol 76, 9877–9887.[CrossRef]
    [Google Scholar]
  8. Chen, H. C., Hofman, F. M., Kung, J. T., Lin, Y. D. & Wu-Hsieh, B. A. ( 2007; ). Both virus and tumor necrosis factor alpha are critical for endothelium damage in a mouse model of dengue virus-induced hemorrhage. J Virol 81, 5518–5526.[CrossRef]
    [Google Scholar]
  9. Cheng, Y., King, N. J. & Kesson, A. M. ( 2004; ). The role of tumor necrosis factor in modulating responses of murine embryo fibroblasts by flavivirus, West Nile. Virology 329, 361–370.[CrossRef]
    [Google Scholar]
  10. Choi, S. H., Park, K. J., Ahn, B. Y., Jung, G., Lai, M. M. & Hwang, S. B. ( 2006; ). Hepatitis C virus nonstructural 5B protein regulates tumor necrosis factor alpha signaling through effects on cellular IκB kinase. Mol Cell Biol 26, 3048–3059.[CrossRef]
    [Google Scholar]
  11. Clyde, K., Kyle, J. L. & Harris, E. ( 2006; ). Recent advances in deciphering viral and host determinants of dengue virus replication and pathogenesis. J Virol 80, 11418–11431.[CrossRef]
    [Google Scholar]
  12. Espina, L. M., Valero, N. J., Hernández, J. M. & Mosquera, J. A. ( 2003; ). Increased apoptosis and expression of tumor necrosis factor-alpha caused by infection of cultured human monocytes with dengue virus. Am J Trop Med Hyg 68, 48–53.
    [Google Scholar]
  13. Gilles, P. N., Fey, G. & Chisari, F. V. ( 1992; ). Tumor necrosis factor alpha negatively regulates hepatitis B virus gene expression in transgenic mice. J Virol 66, 3955–3960.
    [Google Scholar]
  14. Green, S. & Rothman, A. ( 2006; ). Immunopathological mechanisms in dengue and dengue hemorrhagic fever. Curr Opin Infect Dis 19, 429–436. [CrossRef]
    [Google Scholar]
  15. Gualano, R. C., Pryor, M. J., Cauchi, M. R., Wright, P. J. & Davidson, A. D. ( 1998; ). Identification of a major determinant of mouse neurovirulence of dengue virus type 2 using stably cloned genomic-length cDNA. J Gen Virol 79, 437–446.
    [Google Scholar]
  16. Halstead, S. B. ( 2007; ). Dengue. Lancet 370, 1644–1652. [CrossRef]
    [Google Scholar]
  17. Herbein, G. & O'Brien, W. A. ( 2000; ). Tumor necrosis factor (TNF)-alpha and TNF receptors in viral pathogenesis. Proc Soc Exp Biol Med 223, 241–257.[CrossRef]
    [Google Scholar]
  18. Hiscott, J., Kwon, H. & Génin, P. ( 2001; ). Hostile takeovers: viral appropriation of the NF-κB pathway. J Clin Invest 107, 143–151. [CrossRef]
    [Google Scholar]
  19. Hober, D., Poli, L., Roblin, B., Gestas, P., Chungue, E., Granic, G., Imbert, P., Pecarere, J. L., Vergez-Pascal, R. & other authors ( 1993; ). Serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1 beta) in dengue-infected patients. Am J Trop Med Hyg 48, 324–331.
    [Google Scholar]
  20. Kittigul, L., Temprom, W., Sujirarat, D. & Kittigul, C. ( 2000; ). Determination of tumor necrosis factor-alpha levels in dengue virus infected patients by sensitive biotin-streptavidin enzyme-linked immunosorbent assay. J Virol Methods 90, 51–57. [CrossRef]
    [Google Scholar]
  21. Koopman, G., Reutelingsperger, C. P., Kuijten, G. A., Keehnen, R. M., Pals, S. T. & van Oers, M. H. ( 1994; ). Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis. Blood 84, 1415–1420.
    [Google Scholar]
  22. Kurane, I., Innis, B. L., Nimmannitya, S., Nisalak, A., Meager, A., Janus, J. & Ennis, F. A. ( 1991; ). Activation of T lymphocytes in dengue virus infections. High levels of soluble interleukin 2 receptor, soluble CD4, soluble CD8, interleukin 2, and interferon-gamma in sera of children with dengue. J Clin Invest 88, 1473–1480. [CrossRef]
    [Google Scholar]
  23. Li, H. & Lin, X. ( 2008; ). Positive and negative signaling components involved in TNFα-induced NF-κB activation. Cytokine 41, 1–8. [CrossRef]
    [Google Scholar]
  24. Limjindaporn, T., Netsawang, J., Noisakran, S., Thiemmeca, S., Wongwiwat, W., Sudsaward, S., Avirutnan, P., Puttikhunt, C., Kasinrerk, W. & Sriburi, R. ( 2007; ). Sensitization to Fas-mediated apoptosis by dengue virus capsid protein. Biochem Biophys Res Commun 362, 334–339.[CrossRef]
    [Google Scholar]
  25. Luplerdlop, N., Missé, D., Bray, D., Deleuze, V., Gonzalez, J. P., Leardkamolkarn, V., Yssel, H. & Veas, F. ( 2006; ). Dengue-virus-infected dendritic cells trigger vascular leakage through metalloproteinase overproduction. EMBO Rep 7, 1176–1181. [CrossRef]
    [Google Scholar]
  26. 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]
  27. Martina, B. E., Koraka, P. & Osterhaus, A. D. ( 2009; ). Dengue virus pathogenesis: an integrated view. Clin Microbiol Rev 22, 564–581. [CrossRef]
    [Google Scholar]
  28. Marusawa, H., Hijikata, M., Chiba, T. & Shimotohno, K. ( 1999; ). Hepatitis C virus core protein inhibits Fas- and tumor necrosis factor alpha-mediated apoptosis via NF-κB activation. J Virol 73, 4713–4720.
    [Google Scholar]
  29. Medin, C. L., Fitzgerald, K. A. & Rothman, A. L. ( 2005; ). Dengue virus nonstructural protein NS5 induces interleukin-8 transcription and secretion. J Virol 79, 11053–11061. [CrossRef]
    [Google Scholar]
  30. Park, K. J., Choi, S. H., Lee, S. Y., Hwang, S. B. & Lai, M. M. ( 2002; ). Nonstructural 5A protein of hepatitis C virus modulates tumor necrosis factor alpha-stimulated nuclear factor kappa B activation. J Biol Chem 277, 13122–13128. [CrossRef]
    [Google Scholar]
  31. Pavić, I., Polić, B., Crnković, I., Lucin, P., Jonjić, S. & Koszinowski, U. H. ( 1993; ). Participation of endogenous tumour necrosis factor alpha in host resistance to cytomegalovirus infection. J Gen Virol 74, 2215–2223. [CrossRef]
    [Google Scholar]
  32. Perez, A. B., Sierra, B., Garcia, G., Aguirre, E., Babel, N., Alvarez, M., Sanchez, L., Valdes, L., Volk, H. D. & Guzman, M. G. ( 2010; ). Tumor necrosis factor-alpha, transforming growth factor-β1, and interleukin-10 gene polymorphisms: implication in protection or susceptibility to dengue hemorrhagic fever. Hum Immunol 71, 1135–1140. [CrossRef]
    [Google Scholar]
  33. Pryor, M. J., Carr, J. M., Hocking, H., Davidson, A. D., Li, P. & Wright, P. J. ( 2001; ). Replication of dengue virus type 2 in human monocyte-derived macrophages: comparisons of isolates and recombinant viruses with substitutions at amino acid 390 in the envelope glycoprotein. Am J Trop Med Hyg 65, 427–434.
    [Google Scholar]
  34. Pryor, M. J., Rawlinson, S. M., Butcher, R. E., Barton, C. L., Waterhouse, T. A., Vasudevan, S. G., Bardin, P. G., Wright, P. J., Jans, D. A. & Davidson, A. D. ( 2007; ). Nuclear localization of dengue virus nonstructural protein 5 through its importin α/β-recognized nuclear localization sequences is integral to viral infection. Traffic 8, 795–807. [CrossRef]
    [Google Scholar]
  35. Rawlinson, S. M., Pryor, M. J., Wright, P. J. & Jans, D. A. ( 2009; ). CRM1-mediated nuclear export of dengue virus RNA polymerase NS5 modulates interleukin-8 induction and virus production. J Biol Chem 284, 15589–15597.[CrossRef]
    [Google Scholar]
  36. Roberts, J. L., Moretti, P. A., Darrow, A. L., Derian, C. K., Vadas, M. A. & Pitson, S. M. ( 2004; ). An assay for sphingosine kinase activity using biotinylated sphingosine and streptavidin-coated membranes. Anal Biochem 331, 122–129.[CrossRef]
    [Google Scholar]
  37. Sacco, R., Tsutsumi, T., Suzuki, R., Otsuka, M., Aizaki, H., Sakamoto, S., Matsuda, M., Seki, N., Matsuura, Y. & other authors ( 2003; ). Antiapoptotic regulation by hepatitis C virus core protein through up-regulation of inhibitor of caspase-activated DNase. Virology 317, 24–35. [CrossRef]
    [Google Scholar]
  38. Saito, K., Meyer, K., Warner, R., Basu, A., Ray, R. B. & Ray, R. ( 2006; ). Hepatitis C virus core protein inhibits tumor necrosis factor alpha-mediated apoptosis by a protective effect involving cellular FLICE inhibitory protein. J Virol 80, 4372–4379. [CrossRef]
    [Google Scholar]
  39. Shafee, N. & AbuBakar, S. ( 2003; ). Dengue virus type 2 NS3 protease and NS2B-NS3 protease precursor induce apoptosis. J Gen Virol 84, 2191–2195. [CrossRef]
    [Google Scholar]
  40. Shresta, S., Sharar, K. L., Prigozhin, D. M., Beatty, P. R. & Harris, E. ( 2006; ). Murine model for dengue virus-induced lethal disease with increased vascular permeability. J Virol 80, 10208–10217. [CrossRef]
    [Google Scholar]
  41. Shrestha, B., Zhang, B., Purtha, W. E., Klein, R. S. & Diamond, M. S. ( 2008; ). Tumor necrosis factor alpha protects against lethal West Nile virus infection by promoting trafficking of mononuclear leukocytes into the central nervous system. J Virol 82, 8956–8964. [CrossRef]
    [Google Scholar]
  42. Shrivastava, A., Manna, S. K., Ray, R. & Aggarwal, B. B. ( 1998; ). Ectopic expression of hepatitis C virus core protein differentially regulates nuclear transcription factors. J Virol 72, 9722–9728.
    [Google Scholar]
  43. Souza, D. G., Fagundes, C. T., Sousa, L. P., Amaral, F. A., Souza, R. S., Souza, A. L., Kroon, E. G., Sachs, D., Cunha, F. Q. & other authors ( 2009; ). Essential role of platelet-activating factor receptor in the pathogenesis of Dengue virus infection. Proc Natl Acad Sci U S A 106, 14138–14143. [CrossRef]
    [Google Scholar]
  44. Srikiatkhachorn, A., Ajariyakhajorn, C., Endy, T. P., Kalayanarooj, S., Libraty, D. H., Green, S., Ennis, F. A. & Rothman, A. L. ( 2007; ). Virus-induced decline in soluble vascular endothelial growth receptor 2 is associated with plasma leakage in dengue hemorrhagic Fever. J Virol 81, 1592–1600.[CrossRef]
    [Google Scholar]
  45. Wati, S., Li, P., Burrell, C. J. & Carr, J. M. ( 2007; ). Dengue virus (DV) replication in monocyte-derived macrophages is not affected by tumor necrosis factor alpha (TNF-α), and DV infection induces altered responsiveness to TNF-α stimulation. J Virol 81, 10161–10171. [CrossRef]
    [Google Scholar]
  46. Xia, P., Wang, L., Gamble, J. R. & Vadas, M. A. ( 1999; ). Activation of sphingosine kinase by tumor necrosis factor-α inhibits apoptosis in human endothelial cells. J Biol Chem 274, 34499–34505. [CrossRef]
    [Google Scholar]
  47. Xia, P., Wang, L., Moretti, P. A., Albanese, N., Chai, F., Pitson, S. M., D'Andrea, R. J., Gamble, J. R. & Vadas, M. A. ( 2002; ). Sphingosine kinase interacts with TRAF2 and dissects tumor necrosis factor-alpha signaling. J Biol Chem 277, 7996–8003.[CrossRef]
    [Google Scholar]
  48. Yamane, D., Zahoor, M. A., Mohamed, Y. M., Azab, W., Kato, K., Tohya, Y. & Akashi, H. ( 2009; ). Inhibition of sphingosine kinase by bovine viral diarrhea virus NS3 is crucial for efficient viral replication and cytopathogenesis. J Biol Chem 284, 13648–13659. [CrossRef]
    [Google Scholar]
  49. Yang, J. S., Ramanathan, M. P., Muthumani, K., Choo, A. Y., Jin, S. H., Yu, Q. C., Hwang, D. S., Choo, D. K., Lee, M. D. & other authors ( 2002; ). Induction of inflammation by West Nile virus capsid through the caspase-9 apoptotic pathway. Emerg Infect Dis 8, 1379–1384.[CrossRef]
    [Google Scholar]
  50. Yang, M. R., Lee, S. R., Oh, W., Lee, E. W., Yeh, J. Y., Nah, J. J., Joo, Y. S., Shin, J., Lee, H. W. & other authors ( 2008; ). West Nile virus capsid protein induces p53-mediated apoptosis via the sequestration of HDM2 to the nucleolus. Cell Microbiol 10, 165–176.
    [Google Scholar]
  51. 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. [CrossRef]
    [Google Scholar]
  52. Zhu, N., Khoshnan, A., Schneider, R., Matsumoto, M., Dennert, G., Ware, C. & Lai, M. M. ( 1998; ). Hepatitis C virus core protein binds to the cytoplasmic domain of tumor necrosis factor (TNF) receptor 1 and enhances TNF-induced apoptosis. J Virol 72, 3691–3697.
    [Google Scholar]
  53. Zhu, N., Ware, C. F. & Lai, M. M. ( 2001; ). Hepatitis C virus core protein enhances FADD-mediated apoptosis and suppresses TRADD signaling of tumor necrosis factor receptor. Virology 283, 178–187. [CrossRef]
    [Google Scholar]
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