1887

Journal of General Virology header logo

Volume 90, Issue 8

Oligonucleotide array analysis of Toll-like receptors and associated signalling genes in Venezuelan equine encephalitis virus-infected mouse brain Free

Abstract

Venezuelan equine encephalitis (VEE) is an emerging infectious disease. VEE virus (VEEV) may cause lethal infection of the central nervous system in horses and humans. The mechanisms underlying the host immune response to VEEV infection in the brain are not fully understood. Toll-like receptors (TLRs) recognize conserved microbial sequences and induce specific biological responses in the form of proinflammatory cytokine induction. TLR expression in blood following VEEV infection has been reported in non-human primates and TLRs are also upregulated in the brains of mice infected with other alphaviruses. In this study, mice (3–5 weeks old) were infected with V3000, a neurovirulent strain of VEEV, and gene expression of TLRs and their associated signalling molecules was evaluated. VEEV infection resulted in upregulation of , , , and , chemokines, inflammatory cytokines, interferon (IFN), IFN regulatory factors and genes involved in signal transduction such as , , , , , , , , , , and . These results demonstrate the upregulation of TLRs and associated signalling genes following VEEV infection of the brain, with important implications for how VEEV induces inflammation and neurodegeneration.

  • Received:
  • Accepted:
  • Published Online:
SGM
Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.010280-0
2009-08-01
2024-04-24
Loading full text...

Full text loading...

/deliver/fulltext/jgv/90/8/1836.html?itemId=/content/journal/jgv/10.1099/vir.0.010280-0&mimeType=html&fmt=ahah

References

  1. Ahmed M., Brzoza K. L., Hiltbold E. M. 2006; Matrix protein mutant of vesicular stomatitis virus stimulates maturation of myeloid dendritic cells. J Virol 80:2194–2205 [CrossRef]
     [Google Scholar]
  2. Aravalli R. N., Hu S., Lokensgard J. R. 2007; Toll-like receptor 2 signaling is a mediator of apoptosis in herpes simplex virus-infected microglia. J Neuroinflammation 4:11 [CrossRef]
     [Google Scholar]
  3. Babcock A. A., Wirenfeldt M., Holm T., Nielsen H. H., Dissing-Olesen L., Toft-Hansen H., Millward J. M., Landmann R., Rivest S.other authors 2006; Toll-like receptor 2 signaling in response to brain injury: an innate bridge to neuroinflammation. J Neurosci 26:12826–12837 [CrossRef]
     [Google Scholar]
  4. Bottcher T., von Mering M., Ebert S., Meyding-Lamade U., Kuhnt U., Gerber J., Nau R. 2003; Differential regulation of Toll-like receptor mRNAs in experimental murine central nervous system infections. Neurosci Lett 344:17–20 [CrossRef]
     [Google Scholar]
  5. Butchi N. B., Pourciau S., Du M., Morgan T. W., Peterson K. E. 2008; Analysis of the neuroinflammatory response to TLR7 stimulation in the brain: comparison of multiple TLR7 and/or TLR8 agonists. J Immunol 180:7604–7612 [CrossRef]
     [Google Scholar]
  6. Caso J. R., Pradillo J. M., Hurtado O., Lorenzo P., Moro M. A., Lizasoain I. 2007; Toll-like receptor 4 is involved in brain damage and inflammation after experimental stroke. Circulation 115:1599–1608 [CrossRef]
     [Google Scholar]
  7. Chakravarty S., Herkenham M. 2005; Toll-like receptor 4 on nonhematopoietic cells sustains CNS inflammation during endotoxemia, independent of systemic cytokines. J Neurosci 25:1788–1796 [CrossRef]
     [Google Scholar]
  8. Charles P. C., Walters E., Margolis F., Johnston R. E. 1995; Mechanism of neuroinvasion of Venezuelan equine encephalitis virus in the mouse. Virology 208:662–671 [CrossRef]
     [Google Scholar]
  9. Charles P. C., Trgovcich J., Davis N. L., Johnston R. E. 2001; Immunopathogenesis and immune modulation of Venezuelan equine encephalitis virus-induced disease in the mouse. Virology 284:190–202 [CrossRef]
     [Google Scholar]
  10. Chen M., Barnfield C., Naslund T. I., Fleeton M. N., Liljestrom P. 2005; MyD88 expression is required for efficient cross-presentation of viral antigens from infected cells. J Virol 79:2964–2972 [CrossRef]
     [Google Scholar]
  11. Crack P. J., Bray P. J. 2007; Toll-like receptors in the brain and their potential roles in neuropathology. Immunol Cell Biol 85:476–480 [CrossRef]
     [Google Scholar]
  12. Daffis S., Samuel M. A., Suthar M. S., Gale M. Jr, Diamond M. S. 2008; Toll-like receptor 3 has a protective role against West Nile virus infection. J Virol 82:10349–10358 [CrossRef]
     [Google Scholar]
  13. Davis N. L., Grieder F. B., Smith J. F., Greenwald G. F., Valenski M. L., Sellon D. C., Charles P. C., Johnston R. E. 1994; A molecular genetic approach to the study of Venezuelan equine encephalitis virus pathogenesis. Arch Virol Suppl 9:99–109
     [Google Scholar]
  14. Eugenin E. A., Osiecki K., Lopez L., Goldstein H., Calderon T. M., Berman J. W. 2006; CCL2/monocyte chemoattractant protein-1 mediates enhanced transmigration of human immunodeficiency virus (HIV)-infected leukocytes across the blood-brain barrier: a potential mechanism of HIV–CNS invasion and NeuroAIDS. J Neurosci 26:1098–1106 [CrossRef]
     [Google Scholar]
  15. Grieder F. B., Vogel S. N. 1999; Role of interferon and interferon regulatory factors in early protection against Venezuelan equine encephalitis virus infection. Virology 257:106–118 [CrossRef]
     [Google Scholar]
  16. Grieder F. B., Davis N. L., Aronson J. F., Charles P. C., Sellon D. C., Suzuki K., Johnston R. E. 1995; Specific restrictions in the progression of Venezuelan equine encephalitis virus-induced disease resulting from single amino acid changes in the glycoproteins. Virology 206:994–1006 [CrossRef]
     [Google Scholar]
  17. Haase R., Kirschning C. J., Sing A., Schröttner P., Fukase K., Kusumoto S., Wagner H., Heesemann J., Ruckdeschel K. 2003; A dominant role of Toll-like receptor 4 in the signaling of apoptosis in bacteria-faced macrophages. J Immunol 171:4294–4303 [CrossRef]
     [Google Scholar]
  18. Hammamieh R., Barmada M., Ludwig G., Peel S., Koterski N., Jett M. 2007; Blood genomic profiles of exposures to Venezuelan equine encephalitis in Cynomolgus macaques ( Macaca fascicularis . Virol J 4:82 [CrossRef]
     [Google Scholar]
  19. Hawley R. J., Eitzen E. M. Jr 2001; Biological weapons – a primer for microbiologists. Annu Rev Microbiol 55:235–253 [CrossRef]
     [Google Scholar]
  20. Hidaka F., Matsuo S., Muta T., Takeshige K., Mizukami T., Nunoi H. 2006; A missense mutation of the Toll-like receptor 3 gene in a patient with influenza-associated encephalopathy. Clin Immunol 119:188–194 [CrossRef]
     [Google Scholar]
  21. Honda K., Yanai H., Mizutani T., Negishi H., Shimada N., Suzuki N., Ohba Y., Takaoka A., Yeh W. C., Taniguchi T. 2004; Role of a transductional-transcriptional processor complex involving MyD88 and IRF-7 in Toll-like receptor signaling. Proc Natl Acad Sci U S A 101:15416–15421 [CrossRef]
     [Google Scholar]
  22. Jackson A. C., Rossiter J. P. 1997; Apoptotic cell death is an important cause of neuronal injury in experimental Venezuelan equine encephalitis virus infection of mice. Acta Neuropathol 93:349–353 [CrossRef]
     [Google Scholar]
  23. Jackson A. C., SenGupta S. K., Smith J. F. 1991; Pathogenesis of Venezuelan equine encephalitis virus infection in mice and hamsters. Vet Pathol 28:410–418 [CrossRef]
     [Google Scholar]
  24. Kaiser W. J., Offermann M. K. 2005; Apoptosis induced by the toll-like receptor adaptor TRIF is dependent on its receptor interacting protein homotypic interaction motif. J Immunol 174:4942–4952 [CrossRef]
     [Google Scholar]
  25. Koedel U., Merbt U. M., Schmidt C., Angele B., Popp B., Wagner H., Pfister H. W., Kirschning C. J. 2007; Acute brain injury triggers MyD88-dependent, TLR2/4-independent inflammatory responses. Am J Pathol 171:200–213 [CrossRef]
     [Google Scholar]
  26. Koterski J., Twenhafel N., Porter A., Reed D. S., Martino-Catt S., Sobral B., Crasta O., Downey T., DaSilva L. 2007; Gene expression profiling of nonhuman primates exposed to aerosolized Venezuelan equine encephalitis virus. FEMS Immunol Med Microbiol 51:462–472 [CrossRef]
     [Google Scholar]
  27. Kurt-Jones E. A., Chan M., Zhou S., Wang J., Reed G., Bronson R., Arnold M. M., Knipe D. M., Finberg R. W. 2004; Herpes simplex virus 1 interaction with Toll-like receptor 2 contributes to lethal encephalitis. Proc Natl Acad Sci U S A 101:1315–1320 [CrossRef]
     [Google Scholar]
  28. Lang K. S., Navarini A. A., Recher M., Lang P. A., Heikenwalder M., Stecher B., Bergthaler A., Odermatt B., Akira S.other authors 2007; MyD88 protects from lethal encephalitis during infection with vesicular stomatitis virus. Eur J Immunol 37:2434–2440 [CrossRef]
     [Google Scholar]
  29. Mansur D. S., Kroon E. G., Nogueira M. L., Arantes R. M., Rodrigues S. C., Akira S., Gazzinelli R. T., Campos M. A. 2005; Lethal encephalitis in myeloid differentiation factor 88-deficient mice infected with herpes simplex virus 1. Am J Pathol 166:1419–1426 [CrossRef]
     [Google Scholar]
  30. McKimmie C. S., Johnson N., Fooks A. R., Fazakerley J. K. 2005; Viruses selectively upregulate Toll-like receptors in the central nervous system. Biochem Biophys Res Commun 336:925–933 [CrossRef]
     [Google Scholar]
  31. Ménager P., Roux P., Megret F., Bourgeois J. P., Le Sourd A. M., Danckaert A., Lafage M., Prehaud C., Lafon M. 2009; Toll-like receptor 3 (TLR3) plays a major role in the formation of rabies virus Negri bodies. PLoS Pathog 5:e1000315 [CrossRef]
     [Google Scholar]
  32. Moynagh P. N. 2005; TLR signalling and activation of IRFs: revisiting old friends from the NF- κ B pathway. Trends Immunol 26:469–476 [CrossRef]
     [Google Scholar]
  33. Park C., Lee S., Cho I. H., Lee H. K., Kim D., Choi S. Y., Oh S. B., Park K., Kim J. S., Lee S. J. 2006; TLR3-mediated signal induces proinflammatory cytokine and chemokine gene expression in astrocytes: differential signaling mechanisms of TLR3-induced IP-10 and IL-8 gene expression. Glia 53:248–256 [CrossRef]
     [Google Scholar]
  34. Prehaud C., Megret F., Lafage M., Lafon M. 2005; Virus infection switches TLR-3-positive human neurons to become strong producers of beta interferon. J Virol 79:12893–12904 [CrossRef]
     [Google Scholar]
  35. Rolland A., Jouvin-Marche E., Viret C., Faure M., Perron H., Marche P. N. 2006; The envelope protein of a human endogenous retrovirus-W family activates innate immunity through CD14/TLR4 and promotes Th1-like responses. J Immunol 176:7636–7644 [CrossRef]
     [Google Scholar]
  36. Ryzhikov A. B., Ryabchikova E. I., Sergeev A. N., Tkacheva N. V. 1995; Spread of Venezuelan equine encephalitis virus in mice olfactory tract. Arch Virol 140:2243–2254 [CrossRef]
     [Google Scholar]
  37. Saikh K. U., Lee J. S., Kissner T. L., Dyas B., Ulrich R. G. 2003; Toll-like receptor and cytokine expression patterns of CD56+ T cells are similar to natural killer cells in response to infection with Venezuelan equine encephalitis virus replicons. J Infect Dis 188:1562–1570 [CrossRef]
     [Google Scholar]
  38. Schoneboom B. A., Fultz M. J., Miller T. H., McKinney L. C., Grieder F. B. 1999; Astrocytes as targets for Venezuelan equine encephalitis virus infection. J Neurovirol 5:342–354 [CrossRef]
     [Google Scholar]
  39. Schoneboom B. A., Catlin K. M., Marty A. M., Grieder F. B. 2000a; Inflammation is a component of neurodegeneration in response to Venezuelan equine encephalitis virus infection in mice. J Neuroimmunol 109:132–146 [CrossRef]
     [Google Scholar]
  40. Schoneboom B. A., Lee J. S., Grieder F. B. 2000b; Early expression of IFN- α / β and iNOS in the brains of Venezuelan equine encephalitis virus-infected mice. J Interferon Cytokine Res 20:205–215 [CrossRef]
     [Google Scholar]
  41. Sharma A., Bhattacharya B., Puri R. K., Maheshwari R. K. 2008; Venezuelan equine encephalitis virus infection causes modulation of inflammatory and immune response genes in mouse brain. BMC Genomics 9:289 [CrossRef]
     [Google Scholar]
  42. Song L., Pachter J. S. 2004; Monocyte chemoattractant protein-1 alters expression of tight junction-associated proteins in brain microvascular endothelial cells. Microvasc Res 67:78–89 [CrossRef]
     [Google Scholar]
  43. Sørensen L. N., Reinert L. S., Malmgaard L., Bartholdy C., Thomsen A. R., Paludan S. R. 2008; TLR2 and TLR9 synergistically control herpes simplex virus infection in the brain. J Immunol 181:8604–8612 [CrossRef]
     [Google Scholar]
  44. Srivastava A., Henneke P., Visintin A., Morse S. C., Martin V., Watkins C., Paton J. C., Wessels M. R., Golenbock D. T., Malley R. 2005; The apoptotic response to pneumolysin is Toll-like receptor 4 dependent and protects against pneumococcal disease. Infect Immun 73:6479–6487 [CrossRef]
     [Google Scholar]
  45. Stamatovic S. M., Shakui P., Keep R. F., Moore B. B., Kunkel S. L., Van Rooijen N., Andjelkovic A. V. 2005; Monocyte chemoattractant protein-1 regulation of blood–brain barrier permeability. J Cereb Blood Flow Metab 25:593–606 [CrossRef]
     [Google Scholar]
  46. Steele K. E., Davis K. J., Stephan K., Kell W., Vogel P., Hart M. K. 1998; Comparative neurovirulence and tissue tropism of wild-type and attenuated strains of Venezuelan equine encephalitis virus administered by aerosol in C3H/HeN and BALB/c mice. Vet Pathol 35:386–397 [CrossRef]
     [Google Scholar]
  47. Tabeta K., Georgel P., Janssen E., Du X., Hoebe K., Crozat K., Mudd S., Shamel L., Sovath S.other authors 2004; Toll-like receptors 9 and 3 as essential components of innate immune defense against mouse cytomegalovirus infection. Proc Natl Acad Sci U S A 101:3516–3521 [CrossRef]
     [Google Scholar]
  48. Takeda K., Akira S. 2005; Toll-like receptors in innate immunity. Int Immunol 17:1–14
     [Google Scholar]
  49. Town T., Bai F., Wang T., Kaplan A. T., Qian F., Montgomery R. R., Anderson J. F., Flavell R. A., Fikrig E. 2009; Toll-like receptor 7 mitigates lethal West Nile encephalitis via interleukin 23-dependent immune cell infiltration and homing. Immunity 30:242–253 [CrossRef]
     [Google Scholar]
  50. Walter S., Letiembre M., Liu Y., Heine H., Penke B., Hao W., Bode B., Manietta N., Walter J.other authors 2007; Role of the toll-like receptor 4 in neuroinflammation in Alzheimer's disease. Cell Physiol Biochem 20:947–956 [CrossRef]
     [Google Scholar]
  51. Wang T., Town T., Alexopoulou L., Anderson J. F., Fikrig E., Flavell R. A. 2004; Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitis. Nat Med 10:1366–1373 [CrossRef]
     [Google Scholar]
  52. Weaver S. C., Ferro C., Barrera R., Boshell J., Navarro J. C. 2004; Venezuelan equine encephalitis. Annu Rev Entomol 49:141–174 [CrossRef]
     [Google Scholar]
  53. White L. J., Wang J. G., Davis N. L., Johnston R. E. 2001; Role of alpha/beta interferon in Venezuelan equine encephalitis virus pathogenesis: effect of an attenuating mutation in the 5′ untranslated region. J Virol 75:3706–3718 [CrossRef]
     [Google Scholar]
  54. Yoon H. J., Jeon S. B., Suk K., Choi D. K., Hong Y. J., Park E. J. 2008; Contribution of TLR2 to the initiation of ganglioside-triggered inflammatory signaling. Mol Cells 25:99–104
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.010280-0
Loading
Oligonucleotide array analysis of Toll-like receptors and associated signalling genes in Venezuelan equine encephalitis virus-infected mouse brain
J. Gen. Virol. 90, 1836 (2009); https://doi.org/10.1099/vir.0.010280-0
/content/journal/jgv/10.1099/vir.0.010280-0
/content/journal/jgv/10.1099/vir.0.010280-0
Loading

Data & Media loading...

Most cited Most Cited RSS feed

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