1887

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Volume 94, Issue 11

Reduced sphingosine kinase 1 activity in dengue virus type-2 infected cells can be mediated by the 3′ untranslated region of dengue virus type-2 RNA Free

Abstract

Sphingosine kinase 1 (SphK1) is a lipid kinase with important roles including regulation of cell survival. We have previously shown reduced SphK1 activity in cells with an established dengue virus type-2 (DENV-2) infection. In this study, we examined the effect of alterations in SphK1 activity on DENV-2 replication and cell death and determined the mechanisms of the reduction in SphK1 activity. Chemical inhibition or overexpression of SphK1 after established DENV-2 infection had no effect on infectious DENV-2 production, although inhibition of SphK1 resulted in enhanced DENV-2-induced cell death. Reduced SphK1 activity was observed in multiple cell types, regardless of the ability of DENV-2 infection to be cytopathic, and was mediated by a post-translational mechanism. Unlike bovine viral diarrhea virus, where SphK1 activity is decreased by the NS3 protein, SphK1 activity was not affected by DENV-2 NS3 but, instead, was reduced by expression of the terminal 396 bases of the 3′ UTR of DENV-2 RNA. We have previously shown that eukaryotic elongation factor 1A (eEF1A) is a direct activator of SphK1 and here DENV-2 RNA co-localized and co-precipitated with eEF1A from infected cells. We propose that the reduction in SphK1 activity late in DENV-2-infected cells is a consequence of DENV-2 out-competing SphK1 for eEF1A binding and hijacking cellular eEF1A for its own replication strategy, rather than a specific host or virus-induced change in SphK1 to modulate viral replication. Nonetheless, reduced SphK1 activity may have important consequences for survival or death of the infected cell.

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© 2013 SGM
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2013-11-01
2024-04-27
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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 [View Article][PubMed]
     [Google Scholar]
  2. Barr R. K., Lynn H. E., Moretti P. A., Khew-Goodall Y., Pitson S. M. 2008; Deactivation of sphingosine kinase 1 by protein phosphatase 2A. J Biol Chem 283:34994–35002 [View Article][PubMed]
     [Google Scholar]
  3. Bhuvanakantham R., Li J., Tan T. T., Ng M. L. 2010; Human Sec3 protein is a novel transcriptional and translational repressor of flavivirus. Cell Microbiol 12:453–472 [View Article][PubMed]
     [Google Scholar]
  4. Blackwell J. L., Brinton M. A. 1997; Translation elongation factor-1 alpha interacts with the 3′ stem-loop region of West Nile virus genomic RNA. J Virol 71:6433–6444[PubMed]
     [Google Scholar]
  5. 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 [View Article][PubMed]
     [Google Scholar]
  6. Carr J. M., Mahalingam S., Bonder C. S., Pitson S. M. 2013; Sphingosine kinase 1 in viral infections. Rev Med Virol 23:73–84 [View Article][PubMed]
     [Google Scholar]
  7. Chan H., Pitson S. M. 2013; Post-translational regulation of sphingosine kinases. Biochim Biophys Acta 1831:147–156 [View Article][PubMed]
     [Google Scholar]
  8. 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 [View Article][PubMed]
     [Google Scholar]
  9. 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 [View Article][PubMed]
     [Google Scholar]
  10. 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 [View Article][PubMed]
     [Google Scholar]
  11. Davis W. G., Blackwell J. L., Shi P. Y., Brinton M. A. 2007; Interaction between the cellular protein eEF1A and the 3′-terminal stem-loop of West Nile virus genomic RNA facilitates viral minus-strand RNA synthesis. J Virol 81:10172–10187 [View Article][PubMed]
     [Google Scholar]
  12. Diamond D. L., Syder A. J., Jacobs J. M., Sorensen C. M., Walters K. A., Proll S. C., McDermott J. E., Gritsenko M. A., Zhang Q.other authors 2010; Temporal proteome and lipidome profiles reveal hepatitis C virus-associated reprogramming of hepatocellular metabolism and bioenergetics. PLoS Pathog 6:e1000719 [View Article][PubMed]
     [Google Scholar]
  13. Funk A., Truong K., Nagasaki T., Torres S., Floden N., Balmori Melian E., Edmonds J., Dong H., Shi P. Y., Khromykh A. A. 2010; RNA structures required for production of subgenomic flavivirus RNA. J Virol 84:11407–11417 [View Article][PubMed]
     [Google Scholar]
  14. 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[PubMed]
     [Google Scholar]
  15. Halstead S. B. 2007; Dengue. Lancet 370:1644–1652 [View Article][PubMed]
     [Google Scholar]
  16. Hannun Y. A., Obeid L. M. 2008; Principles of bioactive lipid signalling: lessons from sphingolipids. Nat Rev Mol Cell Biol 9:139–150 [View Article][PubMed]
     [Google Scholar]
  17. Heaton N. S., Randall G. 2011; Dengue virus and autophagy. Viruses 3:1332–1341 [View Article][PubMed]
     [Google Scholar]
  18. Heaton N. S., Perera R., Berger K. L., Khadka S., Lacount D. J., Kuhn R. J., Randall G. 2010; Dengue virus nonstructural protein 3 redistributes fatty acid synthase to sites of viral replication and increases cellular fatty acid synthesis. Proc Natl Acad Sci U S A 107:17345–17350 [View Article][PubMed]
     [Google Scholar]
  19. Helbig K. J., Lau D. T., Semendric L., Harley H. A., Beard M. R. 2005; Analysis of ISG expression in chronic hepatitis C identifies viperin as a potential antiviral effector. Hepatology 42:702–710 [View Article][PubMed]
     [Google Scholar]
  20. Hirata Y., Ikeda K., Sudoh M., Tokunaga Y., Suzuki A., Weng L., Ohta M., Tobita Y., Okano K.other authors 2012; Self-enhancement of hepatitis C virus replication by promotion of specific sphingolipid biosynthesis. PLoS Pathog 8:e1002860 [View Article][PubMed]
     [Google Scholar]
  21. 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-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in dengue-infected patients. Am J Trop Med Hyg 48:324–331[PubMed]
     [Google Scholar]
  22. Jarman K. E., Moretti P. A., Zebol J. R., Pitson S. M. 2010; Translocation of sphingosine kinase 1 to the plasma membrane is mediated by calcium- and integrin-binding protein 1. J Biol Chem 285:483–492 [View Article][PubMed]
     [Google Scholar]
  23. Leclercq T. M., Pitson S. M. 2006; Cellular signalling by sphingosine kinase and sphingosine 1-phosphate. IUBMB Life 58:467–472 [View Article][PubMed]
     [Google Scholar]
  24. Leclercq T. M., Moretti P. A., Vadas M. A., Pitson S. M. 2008; Eukaryotic elongation factor 1A interacts with sphingosine kinase and directly enhances its catalytic activity. J Biol Chem 283:9606–9614 [View Article][PubMed]
     [Google Scholar]
  25. Leclercq T. M., Moretti P. A., Pitson S. M. 2011; Guanine nucleotides regulate sphingosine kinase 1 activation by eukaryotic elongation factor 1A and provide a mechanism for eEF1A-associated oncogenesis. Oncogene 30:372–378 [View Article][PubMed]
     [Google Scholar]
  26. Li H., Lin X. 2008; Positive and negative signaling components involved in TNFα-induced NF-κB activation. Cytokine 41:1–8 [View Article][PubMed]
     [Google Scholar]
  27. Li D., Wei T., Abbott C. M., Harrich D. 2013; The unexpected roles of eukaryotic translation elongation factors in RNA virus replication and pathogenesis. Microbiol Mol Biol Rev 77:253–266 [View Article][PubMed]
     [Google Scholar]
  28. Loveridge C., Tonelli F., Leclercq T., Lim K. G., Long J. S., Berdyshev E., Tate R. J., Natarajan V., Pitson S. M.other authors 2010; The sphingosine kinase 1 inhibitor 2-(p-hydroxyanilino)-4-(p-chlorophenyl)thiazole induces proteasomal degradation of sphingosine kinase 1 in mammalian cells. J Biol Chem 285:38841–38852 [View Article][PubMed]
     [Google Scholar]
  29. Maceyka M., Milstien S., Spiegel S. 2009; Sphingosine-1-phosphate: the Swiss army knife of sphingolipid signaling. J Lipid Res 50:SupplS272–S276 [View Article][PubMed]
     [Google Scholar]
  30. Machesky N. J., Zhang G., Raghavan B., Zimmerman P., Kelly S. L., Merrill A. H. Jr, Waldman W. J., Van Brocklyn J. R., Trgovcich J. 2008; Human cytomegalovirus regulates bioactive sphingolipids. J Biol Chem 283:26148–26160 [View Article][PubMed]
     [Google Scholar]
  31. MacPherson J. I., Sidders B., Wieland S., Zhong J., Targett-Adams P., Lohmann V., Backes P., Delpuech-Adams O., Chisari F.other authors 2011; An integrated transcriptomic and meta-analysis of hepatoma cells reveals factors that influence susceptibility to HCV infection. PLoS ONE 6:e25584 [View Article][PubMed]
     [Google Scholar]
  32. Martina B. E., Koraka P., Osterhaus A. D. 2009; Dengue virus pathogenesis: an integrated view. Clin Microbiol Rev 22:564–581 [View Article][PubMed]
     [Google Scholar]
  33. Monick M. M., Cameron K., Powers L. S., Butler N. S., McCoy D., Mallampalli R. K., Hunninghake G. W. 2004; Sphingosine kinase mediates activation of extracellular signal-related kinase and Akt by respiratory syncytial virus. Am J Respir Cell Mol Biol 30:844–852 [View Article][PubMed]
     [Google Scholar]
  34. Perera R., Riley C., Isaac G., Hopf-Jannasch A. S., Moore R. J., Weitz K. W., Pasa-Tolic L., Metz T. O., Adamec J., Kuhn R. J. 2012; Dengue virus infection perturbs lipid homeostasis in infected mosquito cells. PLoS Pathog 8:e1002584 [View Article][PubMed]
     [Google Scholar]
  35. Pham D. H., Moretti P. A., Goodall G. J., Pitson S. M. 2008; Attenuation of leakiness in doxycycline-inducible expression via incorporation of 3′ AU-rich mRNA destabilizing elements. Biotechniques 45:155–162 [View Article][PubMed]
     [Google Scholar]
  36. Pitman M. R., Pitson S. M. 2010; Inhibitors of the sphingosine kinase pathway as potential therapeutics. Curr Cancer Drug Targets 10:354–367 [View Article][PubMed]
     [Google Scholar]
  37. Pitman M. R., Barr R. K., Gliddon B. L., Magarey A. M., Moretti P. A., Pitson S. M. 2011; A critical role for the protein phosphatase 2A B′α regulatory subunit in dephosphorylation of sphingosine kinase 1. Int J Biochem Cell Biol 43:342–347 [View Article][PubMed]
     [Google Scholar]
  38. Pitman M. R., Pham D. H., Pitson S. M. 2012; Isoform-selective assays for sphingosine kinase activity. Methods Mol Biol 874:21–31 [View Article][PubMed]
     [Google Scholar]
  39. Pitson S. M. 2011; Regulation of sphingosine kinase and sphingolipid signaling. Trends Biochem Sci 36:97–107 [View Article][PubMed]
     [Google Scholar]
  40. Pitson S. M., Moretti P. A., Zebol J. R., Xia P., Gamble J. R., Vadas M. A., D’Andrea R. J., Wattenberg B. W. 2000; Expression of a catalytically inactive sphingosine kinase mutant blocks agonist-induced sphingosine kinase activation. A dominant-negative sphingosine kinase. J Biol Chem 275:33945–33950 [View Article][PubMed]
     [Google Scholar]
  41. Pitson S. M., Moretti P. A., Zebol J. R., Zareie R., Derian C. K., Darrow A. L., Qi J., D’Andrea R. J., Bagley C. J.other authors 2002; The nucleotide-binding site of human sphingosine kinase 1. J Biol Chem 277:49545–49553 [View Article][PubMed]
     [Google Scholar]
  42. Pitson S. M., Moretti P. A., Zebol J. R., Lynn H. E., Xia P., Vadas M. A., Wattenberg B. W. 2003; Activation of sphingosine kinase 1 by ERK1/2-mediated phosphorylation. EMBO J 22:5491–5500 [View Article][PubMed]
     [Google Scholar]
  43. 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[PubMed]
     [Google Scholar]
  44. Rothman A. L. 2011; Immunity to dengue virus: a tale of original antigenic sin and tropical cytokine storms. Nat Rev Immunol 11:532–543 [View Article][PubMed]
     [Google Scholar]
  45. Seo Y. J., Blake C., Alexander S., Hahm B. 2010; Sphingosine 1-phosphate-metabolizing enzymes control influenza virus propagation and viral cytopathogenicity. J Virol 84:8124–8131 [View Article][PubMed]
     [Google Scholar]
  46. 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 [View Article][PubMed]
     [Google Scholar]
  47. Simmons C. P., Farrar J. J., van Vinh Chau N., Wills B. 2012; Dengue. N Engl J Med 366:1423–1432 [View Article][PubMed]
     [Google Scholar]
  48. Takabe K., Paugh S. W., Milstien S., Spiegel S. 2008; “Inside-out” signaling of sphingosine-1-phosphate: therapeutic targets. Pharmacol Rev 60:181–195 [View Article][PubMed]
     [Google Scholar]
  49. Vandermeeren A. M., Gómez C. E., Patiño C., Domingo-Gil E., Guerra S., González J. M., Esteban M. 2008; Subcellular forms and biochemical events triggered in human cells by HCV polyprotein expression from a viral vector. Virol J 5:102 [View Article][PubMed]
     [Google Scholar]
  50. Warren K., Wei T., Li D., Qin F., Warrilow D., Lin M. H., Sivakumaran H., Apolloni A., Abbott C. M.other authors 2012; Eukaryotic elongation factor 1 complex subunits are critical HIV-1 reverse transcription cofactors. Proc Natl Acad Sci U S A 109:9587–9592 [View Article][PubMed]
     [Google Scholar]
  51. 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 [View Article][PubMed]
     [Google Scholar]
  52. Wati S., Rawlinson S. M., Ivanov R. A., Dorstyn L., Beard M. R., Jans D. A., Pitson S. M., Burrell C. J., Li P., Carr J. M. 2011; Tumour necrosis factor alpha (TNF-α) stimulation of cells with established dengue virus type 2 infection induces cell death that is accompanied by a reduced ability of TNF-α to activate nuclear factor κB and reduced sphingosine kinase-1 activity. J Gen Virol 92:807–818 [View Article][PubMed]
     [Google Scholar]
  53. Wattenberg B. W., Pitson S. M., Raben D. M. 2006; The sphingosine and diacylglycerol kinase superfamily of signaling kinases: localization as a key to signaling function. J Lipid Res 47:1128–1139 [View Article][PubMed]
     [Google Scholar]
  54. 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-α signaling. J Biol Chem 277:7996–8003 [View Article][PubMed]
     [Google Scholar]
  55. 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 [View Article][PubMed]
     [Google Scholar]
  56. 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 [View Article][PubMed]
     [Google Scholar]
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Reduced sphingosine kinase 1 activity in dengue virus type-2 infected cells can be mediated by the 3′ untranslated region of dengue virus type-2 RNA
J. Gen. Virol. 94, 2437 (2013); https://doi.org/10.1099/vir.0.055616-0
/content/journal/jgv/10.1099/vir.0.055616-0
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