Dengue virus regulates type I interferon signalling in a strain-dependent manner in human cell lines Free

Abstract

Outbreaks of dengue disease are constant threats to tropical and subtropical populations but range widely in severity, from mild to haemorrhagic fevers, for reasons that are still elusive. We investigated the interferon (IFN) response in infected human cell lines A549 and HepG2, using two strains (NGC and TSV01) of dengue serotype 2 (DEN2) and found that the two viruses exhibited a marked difference in inducing type I IFN response. While TSV01 infection led to activation of type I antiviral genes such as EIF2AK2 (PKR), OAS, ADAR and MX, these responses were absent in NGC-infected cells. Biochemical analysis revealed that NGC but not TSV01 suppressed STAT-1 and STAT-2 activation in response to type I IFN ( and ). However, these two strains did not differ in their response to type II IFN (). Although unable to suppress IFN signalling, TSV01 infection caused a weaker IFN- induction compared with NGC, suggesting an alternative mechanism of innate immune escape. We extended our study to clinical isolates of various serotypes and found that while MY10245 (DEN2) and MY22713 (DEN4) could suppress the IFN response in a similar fashion to NGC, three other strains of dengue [EDEN167 (DEN1), MY02569 (DEN1) and MY10340 (DEN2)] were unable to suppress the IFN response, suggesting that this difference is strain-dependent but not serotype-specific. Our report indicates the existence of a strain-specific virulence factor that may impact on disease severity.

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2008-12-01
2024-03-28
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References

  1. Ajariyakhajorn C., Mammen M. P. Jr, Endy T. P., Gettayacamin M., Nisalak A., Nimmannitya S., Libraty D. H. 2005; Randomized, placebo-controlled trial of nonpegylated and pegylated forms of recombinant human alpha interferon 2a for suppression of dengue virus viremia in rhesus monkeys. Antimicrob Agents Chemother 49:4508–4514 [CrossRef]
    [Google Scholar]
  2. Alvarez D. E., De Lella Ezcurra A. L., Fucito S., Gamarnik A. V. 2005; Role of RNA structures present at the 3′UTR of dengue virus on translation, RNA synthesis, and viral replication. Virology 339:200–212 [CrossRef]
    [Google Scholar]
  3. Bravo J. R., Guzmán M. G., Kouri G. P. 1987; Why dengue haemorrhagic fever in Cuba? 1. Individual risk factors for dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS).. Trans R Soc Trop Med Hyg 81:816–820 [CrossRef]
    [Google Scholar]
  4. Cheng G., Zhong J., Chisari F. V. 2006; Inhibition of dsRNA-induced signaling in hepatitis C virus-infected cells by NS3 protease-dependent and -independent mechanisms. Proc Natl Acad Sci U S A 103:8499–8504 [CrossRef]
    [Google Scholar]
  5. Cologna R., Armstrong P. M., Rico-Hesse R. 2005; Selection for virulent dengue viruses occurs in humans and mosquitoes. J Virol 79:853–859 [CrossRef]
    [Google Scholar]
  6. Diamond M. S., Roberts T. G., Edgil D., Lu B., Ernst J., Harris E. 2000; Modulation of Dengue virus infection in human cells by alpha, beta, and gamma interferons. J Virol 74:4957–4966 [CrossRef]
    [Google Scholar]
  7. Edgil D., Diamond M. S., Holden K. L., Paranjape S. M., Harris E. 2003; Translation efficiency determines differences in cellular infection among dengue virus type 2 strains. Virology 317:275–290 [CrossRef]
    [Google Scholar]
  8. Fagbami A. H., Mataika J. U., Shrestha M., Gubler D. J. 1995; Dengue type 1 epidemic with haemorrhagic manifestations in Fiji, 1989–90. Bull World Health Organ 73:291–297
    [Google Scholar]
  9. Fink J., Gu F., Ling L., Tolfvenstam T., Olfat F., Chin K. C., Aw P., George J., Kuznetsov V. A. other authors 2007; Host gene expression profiling of dengue virus infection in cell lines and patients. PLoS Negl Trop Dis 1:e86 [CrossRef]
    [Google Scholar]
  10. Gale M. Jr, Foy E. M. 2005; Evasion of intracellular host defence by hepatitis C virus. Nature 436:939–945 [CrossRef]
    [Google Scholar]
  11. Gubler D. J., Reed D., Rosen L., Hitchcock J. R. Jr 1978; Epidemiologic, clinical, and virologic observations on dengue in the Kingdom of Tonga. Am J Trop Med Hyg 27:581–589
    [Google Scholar]
  12. Gubler D. J., Suharyono W., Lubis I., Eram S., Gunarso S. 1981; Epidemic dengue 3 in central Java, associated with low viremia in man. Am J Trop Med Hyg 30:1094–1099
    [Google Scholar]
  13. Haller O., Kochs G., Weber F. 2006; The interferon response circuit: induction and suppression by pathogenic viruses. Virology 344:119–130 [CrossRef]
    [Google Scholar]
  14. Halstead S. B. 2003; Neutralization and antibody-dependent enhancement of dengue viruses. Adv Virus Res 60:421–467
    [Google Scholar]
  15. Hibberd M. L., Ling L., Tolfvenstam T., Mitchell W., Wong C., Kuznetsov V. A., George J., Ong S. H., Ruan Y. other authors 2006; A genomics approach to understanding host response during dengue infection. Novartis Found Symp 277:206–214 discussion 214–7, 251–3
    [Google Scholar]
  16. Ho L. J., Hung L. F., Weng C. Y., Wu W. L., Chou P., Lin Y. L., Chang D. M., Tai T. Y., Lai J. H. 2005; Dengue virus type 2 antagonizes IFN- α but not IFN- λ antiviral effect via down-regulating Tyk2-STAT signaling in the human dendritic cell. J Immunol 174:8163–8172 [CrossRef]
    [Google Scholar]
  17. Jones M., Davidson A., Hibbert L., Gruenwald P., Schlaak J., Ball S., Foster G. R., Jacobs M. 2005; Dengue virus inhibits alpha interferon signaling by reducing STAT2 expression. J Virol 79:5414–5420 [CrossRef]
    [Google Scholar]
  18. Kochel T. J., Watts D. M., Halstead S. B., Hayes C. G., Espinoza A., Felices V., Caceda R., Bautista C. T., Montoya Y. other authors 2002; Effect of dengue-1 antibodies on American dengue-2 viral infection and dengue haemorrhagic fever. Lancet 360:310–312 [CrossRef]
    [Google Scholar]
  19. Kubota T., Yokosawa N., Yokota S., Fujii N. 2002; Association of mumps virus V protein with RACK1 results in dissociation of STAT-1 from the alpha interferon receptor complex. J Virol 76:12676–12682 [CrossRef]
    [Google Scholar]
  20. Leitmeyer K. C., Vaughn D. W., Watts D. M., Salas R., Villalobos I., de Chacon, Ramos C., Rico-Hesse R. 1999; Dengue virus structural differences that correlate with pathogenesis. J Virol 73:4738–4747
    [Google Scholar]
  21. Luo X. M., Ross A. C. 2005; Physiological and receptor-selective retinoids modulate interferon γ signaling by increasing the expression, nuclear localization, and functional activity of Interferon regulatory factor-1. J Biol Chem 280:36228–36236 [CrossRef]
    [Google Scholar]
  22. Messer W. B., Vitarana U. T., Sivananthan K., Elvtigala J., Preethimala L. D., Ramesh R., Withana N., Gubler D. J., De Silva A. M. 2002; Epidemiology of dengue in Sri Lanka before and after the emergence of epidemic dengue hemorrhagic fever. Am J Trop Med Hyg 66:765–773
    [Google Scholar]
  23. Messer W. B., Gubler D. J., Harris E., Sivananthan K., de Silva A. M. 2003; Emergence and global spread of a dengue serotype 3, subtype III virus. Emerg Infect Dis 9:800–809 [CrossRef]
    [Google Scholar]
  24. Miller S., Sparacio S., Bartenschlager R. 2006; Subcellular localization and membrane topology of the Dengue virus type 2 Non-structural protein 4B. J Biol Chem 281:8854–8863 [CrossRef]
    [Google Scholar]
  25. Munoz-Jordan J. L., Sanchez-Burgos G. G., Laurent-Rolle M., Garcia-Sastre A. 2003; Inhibition of interferon signaling by dengue virus. Proc Natl Acad Sci U S A 100:14333–14338 [CrossRef]
    [Google Scholar]
  26. Munoz-Jordan J. L., Laurent-Rolle M., Ashour J., Martinez-Sobrido L., Ashok M., Lipkin W. I., Garcia-Sastre A. 2005; Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol 79:8004–8013 [CrossRef]
    [Google Scholar]
  27. Pandey B. D., Igarashi A. 2000; Severity-related molecular differences among nineteen strains of dengue type 2 viruses. Microbiol Immunol 44:179–188 [CrossRef]
    [Google Scholar]
  28. Rico-Hesse R., Harrison L. M., Salas R. A., Tovar D., Nisalak A., Ramos C., Boshell J., de Mesa M. T., Nogueira R. M., da Rosa A. T. 1997; Origins of dengue type 2 viruses associated with increased pathogenicity in the Americas. Virology 230:244–251 [CrossRef]
    [Google Scholar]
  29. Sabin A. B. 1952; Research on dengue during World War II. Am J Trop Med Hyg 1:30–50
    [Google Scholar]
  30. Seth R. B., Sun L., Ea C. K., Chen Z. J. 2005; Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF- κ B and IRF 3. Cell 122:669–682 [CrossRef]
    [Google Scholar]
  31. Seth R. B., Sun L., Chen Z. J. 2006; Antiviral innate immunity pathways. Cell Res 16:141–147 [CrossRef]
    [Google Scholar]
  32. Shaw M. L., Garcia-Sastre A., Palese P., Basler C. F. 2004; Nipah virus V and W proteins have a common STAT1-binding domain yet inhibit STAT1 activation from the cytoplasmic and nuclear compartments, respectively. J Virol 78:5633–5641 [CrossRef]
    [Google Scholar]
  33. Shresta S., Kyle J. L., Snider H. M., Basavapatna M., Beatty P. R., Harris E. 2004; Interferon-dependent immunity is essential for resistance to primary dengue virus infection in mice, whereas T- and B-cell-dependent immunity are less critical. J Virol 78:2701–2710 [CrossRef]
    [Google Scholar]
  34. Watts D. M., Porter K. R., Putvatana P., Vasquez B., Calampa C., Hayes C. G., Halstead S. B. 1999; Failure of secondary infection with American genotype dengue 2 to cause dengue haemorrhagic fever. Lancet 354:1431–1434 [CrossRef]
    [Google Scholar]
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