1887

Abstract

The flavivirus (WNV) can cause fatal encephalitis in humans and mice. It has recently been demonstrated, in an experimental model using WNV strain Sarafend and C57BL/6 mice, that both virus- and immune-mediated pathology is involved in WNV encephalitis, with CD8 T cells being the dominant subpopulation of lymphocyte infiltrates in the brain. Here, the role of activated WNV-immune CD8 T cells in mouse WNV encephalitis was investigated further. Passive transfer of WNV-immune CD8 T cells reduced mortality significantly and prolonged survival times of mice infected with WNV. Early infiltration of WNV-immune CD8 T cells into infected brains is shown, suggesting a beneficial contribution of these lymphocytes to recovery from encephalitis. This antiviral function was not markedly mediated by gamma interferon (IFN-), as a deficiency in IFN- did not affect mortality to two strains of WNV (Sarafend and Kunjin) or brain virus titres significantly. The cytolytic potential, as well as precursor frequency, of WNV-immune CD8 T cells were not altered by the absence of IFN-. This was reflected in transfer experiments of WNV-immune CD8 T cells from IFN- mice into WNV-infected wild-type mice, which showed that IFN--deficient T cells were as effective as those from WNV-immune wild-type mice in ameliorating disease outcome. It is speculated here that one of the pleiotropic functions of IFN- is mimicked by WNV-Sarafend-mediated upregulation of cell-surface expression of major histocompatibility complex antigens, which may explain the lack of phenotype of IFN- mice in response to WNV.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.81306-0
2006-12-01
2019-11-13
Loading full text...

Full text loading...

/deliver/fulltext/jgv/87/12/3599.html?itemId=/content/journal/jgv/10.1099/vir.0.81306-0&mimeType=html&fmt=ahah

References

  1. Alsharifi, M., Lobigs, M., Simon, M. M., Kersten, A., Müller, K., Koskinen, A., Lee, E. & Müllbacher, A. ( 2006; ). NK cell-mediated immunopathology during an acute viral infection of the CNS. Eur J Immunol 36, 887–896.[CrossRef]
    [Google Scholar]
  2. Bartholdy, C., Christensen, J. P., Wodarz, D. & Thomsen, A. R. ( 2000; ). Persistent virus infection despite chronic cytotoxic T-lymphocyte activation in gamma interferon-deficient mice infected with lymphocytic choriomeningitis virus. J Virol 74, 10304–10311.[CrossRef]
    [Google Scholar]
  3. Beasley, D. W. C., Li, L., Suderman, M. T. & Barrett, A. D. T. ( 2002; ). Mouse neuroinvasive phenotype of West Nile virus strains varies depending upon virus genotype. Virology 296, 17–23.[CrossRef]
    [Google Scholar]
  4. Bergmann, C. C., Parra, B., Hinton, D. R., Chandran, R., Morrison, M. & Stohlman, S. A. ( 2003; ). Perforin-mediated effector function within the central nervous system requires IFN-γ-mediated MHC up-regulation. J Immunol 170, 3204–3213.[CrossRef]
    [Google Scholar]
  5. Bergmann, C. C., Parra, B., Hinton, D. R., Ramakrishna, C., Dowdell, K. C. & Stohlman, S. A. ( 2004; ). Perforin and gamma interferon-mediated control of coronavirus central nervous system infection by CD8 T cells in the absence of CD4 T cells. J Virol 78, 1739–1750.[CrossRef]
    [Google Scholar]
  6. Biron, C. A. ( 1994; ). Cytokines in the generation of immune responses to, and resolution of, virus infection. Curr Opin Immunol 6, 530–538.[CrossRef]
    [Google Scholar]
  7. Blanden, R. V. ( 1970; ). Mechanisms of recovery from a generalized viral infection: mousepox. I. The effects of anti-thymocyte serum. J Exp Med 132, 1035–1054.[CrossRef]
    [Google Scholar]
  8. Boehm, U., Klamp, T., Groot, M. & Howard, J. C. ( 1997; ). Cellular responses to interferon-γ. Annu Rev Immunol 15, 749–795.[CrossRef]
    [Google Scholar]
  9. Cantin, E., Tanamachi, B. & Openshaw, H. ( 1999; ). Role for gamma interferon in control of herpes simplex virus type 1 reactivation. J Virol 73, 3418–3423.
    [Google Scholar]
  10. Chambers, T. J. & Diamond, M. S. ( 2003; ). Pathogenesis of flavivirus encephalitis. Adv Virus Res 60, 273–342.
    [Google Scholar]
  11. Dalton, D. K., Pitts-Meek, S., Keshav, S., Figari, I. S., Bradley, A. & Stewart, T. A. ( 1993; ). Multiple defects of immune cell function in mice with disrupted interferon-γ genes. Science 259, 1739–1742.[CrossRef]
    [Google Scholar]
  12. Guidotti, L. G., McClary, H., Loudis, J. M. & Chisari, F. V. ( 2000; ). Nitric oxide inhibits hepatitis B virus replication in the livers of transgenic mice. J Exp Med 191, 1247–1252.[CrossRef]
    [Google Scholar]
  13. Halevy, M., Akov, Y., Ben-Nathan, D., Kobiler, D., Lachmi, B. & Lustig, S. ( 1994; ). Loss of active neuroinvasiveness in attenuated strains of West Nile virus: pathogenicity in immunocompetent and SCID mice. Arch Virol 137, 355–370.[CrossRef]
    [Google Scholar]
  14. Hall, R. A., Burgess, G. W., Kay, B. H. & Clancy, P. ( 1991; ). Monoclonal antibodies to Kunjin and Kokobera viruses. Immunol Cell Biol 69, 47–49.[CrossRef]
    [Google Scholar]
  15. Henkart, P. A. ( 1994; ). Lymphocyte-mediated cytotoxicity: two pathways and multiple effector molecules. Immunity 1, 343–346.[CrossRef]
    [Google Scholar]
  16. Huang, S., Hendriks, W., Althage, A., Hemmi, S., Bluethmann, H., Kamijo, R., Vilcek, J., Zinkernagel, R. M. & Aguet, M. ( 1993; ). Immune response in mice that lack the interferon-γ receptor. Science 259, 1742–1745.[CrossRef]
    [Google Scholar]
  17. Kagi, D., Ledermann, B., Burki, K., Zinkernagel, R. M. & Hengartner, H. ( 1995; ). Lymphocyte-mediated cytotoxicity in vitro and in vivo: mechanisms and significance. Immunol Rev 146, 95–115.[CrossRef]
    [Google Scholar]
  18. Karupiah, G., Chen, J.-H., Mahalingam, S., Nathan, C. F. & MacMicking, J. D. ( 1998a; ). Rapid interferon γ-dependent clearance of influenza A virus and protection from consolidating pneumonitis in nitric oxide synthase 2-deficient mice. J Exp Med 188, 1541–1546.[CrossRef]
    [Google Scholar]
  19. Karupiah, G., Chen, J. H., Nathan, C. F., Mahalingam, S. & MacMicking, J. D. ( 1998b; ). Identification of Nitric oxide synthase 2 as an innate resistance locus against ectromelia virus infection. J Virol 72, 7703–7706.
    [Google Scholar]
  20. Kesson, A. M., Blanden, R. V. & Mullbacher, A. ( 1987; ). The primary in vivo murine cytotoxic T cell response to the flavivirus, West Nile. J Gen Virol 68, 2001–2006.[CrossRef]
    [Google Scholar]
  21. King, N. J. C. & Kesson, A. M. ( 2003; ). Interaction of flaviviruses with cells of the vertebrate host and decoy of the immune response. Immunol Cell Biol 81, 207–216.[CrossRef]
    [Google Scholar]
  22. King, N. J. C., Shrestha, B. & Kesson, A. M. ( 2003; ). Immune modulation by flaviviruses. Adv Virus Res 60, 121–155.
    [Google Scholar]
  23. Komatsu, T., Bi, Z. & Reiss, C. S. ( 1996; ). Interferon-γ induced type I nitric oxide synthase activity inhibits viral replication in neurons. J Neuroimmunol 68, 101–108.[CrossRef]
    [Google Scholar]
  24. Landolfo, S., Gariglio, M., Gribaudo, G., Jemma, C., Giovarelli, M. & Cavallo, G. ( 1988; ). Interferon-γ is not an antiviral, but a growth-promoting factor for T lymphocytes. Eur J Immunol 18, 503–509.[CrossRef]
    [Google Scholar]
  25. Licon Luna, R. M., Lee, E., Mullbacher, A., Blanden, R. V., Langman, R. & Lobigs, M. ( 2002; ). Lack of both Fas ligand and perforin protects from flavivirus-mediated encephalitis in mice. J Virol 76, 3202–3211.[CrossRef]
    [Google Scholar]
  26. Liu, T. & Chambers, T. J. ( 2001; ). Yellow fever virus encephalitis: properties of the brain-associated T-cell response during virus clearance in normal and gamma interferon-deficient mice and requirement for CD4+ lymphocytes. J Virol 75, 2107–2118.[CrossRef]
    [Google Scholar]
  27. Liu, Y., King, N., Kesson, A., Blanden, R. V. & Müllbacher, A. ( 1988; ). West Nile virus infection modulates the expression of class I and class II MHC antigens on astrocytes in vitro. Ann N Y Acad Sci 540, 483–485.[CrossRef]
    [Google Scholar]
  28. Liu, Y., Blanden, R. V. & Mullbacher, A. ( 1989a; ). Identification of cytolytic lymphocytes in West Nile virus-infected murine central nervous system. J Gen Virol 70, 565–573.[CrossRef]
    [Google Scholar]
  29. Liu, Y., King, N., Kesson, A., Blanden, R. V. & Mullbacher, A. ( 1989b; ). Flavivirus infection up-regulates the expression of class I and class II major histocompatibility antigens on and enhances T cell recognition of astrocytes in vitro. J Neuroimmunol 21, 157–168.[CrossRef]
    [Google Scholar]
  30. Lobigs, M., Müllbacher, A. & Regner, M. ( 2003a; ). MHC class I up-regulation by flaviviruses: immune interaction with unknown advantage to host or pathogen. Immunol Cell Biol 81, 217–223.[CrossRef]
    [Google Scholar]
  31. Lobigs, M., Müllbacher, A., Wang, Y., Pavy, M. & Lee, E. ( 2003b; ). Role of type I and type II interferon responses in recovery from infection with an encephalitic flavivirus. J Gen Virol 84, 567–572.[CrossRef]
    [Google Scholar]
  32. Lučin, P., Pavić, I., Polić, B., Jonjić, S. & Koszinowski, U. H. ( 1992; ). Gamma interferon-dependent clearance of cytomegalovirus infection in salivary glands. J Virol 66, 1977–1984.
    [Google Scholar]
  33. Mo, X. Y., Tripp, R. A., Sangster, M. Y. & Doherty, P. C. ( 1997; ). The cytotoxic T-lymphocyte response to Sendai virus is unimpaired in the absence of gamma interferon. J Virol 71, 1906–1910.
    [Google Scholar]
  34. Momburg, F., Müllbacher, A. & Lobigs, M. ( 2001; ). Modulation of transporter associated with antigen processing (TAP)-mediated peptide import into the endoplasmic reticulum by flavivirus infection. J Virol 75, 5663–5671.[CrossRef]
    [Google Scholar]
  35. Müllbacher, A. & King, N. J. C. ( 1989; ). Differential target cell susceptibility to SFV-immune cytotoxic T-cells. Arch Virol 107, 97–109.[CrossRef]
    [Google Scholar]
  36. Müllbacher, A. & Lobigs, M. ( 1995; ). Up-regulation of MHC class I by flavivirus-induced peptide translocation into the endoplasmic reticulum. Immunity 3, 207–214.[CrossRef]
    [Google Scholar]
  37. Müllbacher, A., Marshall, I. D. & Ferris, P. ( 1986; ). Classification of Barmah Forest virus as an alphavirus using cytotoxic T cell assays. J Gen Virol 67, 295–299.[CrossRef]
    [Google Scholar]
  38. Müllbacher, A., Lobigs, M., Hla, R. T., Tran, T., Stehle, T. & Simon, M. M. ( 2002; ). Antigen-dependent release of IFN-γ by cytotoxic T cells up-regulates Fas on target cells and facilitates exocytosis-independent specific target cell lysis. J Immunol 169, 145–150.[CrossRef]
    [Google Scholar]
  39. Müllbacher, A., Lobigs, M. & Lee, E. ( 2003; ). Immunobiology of mosquito-borne encephalitic flaviviruses. Adv Virus Res 60, 87–120.
    [Google Scholar]
  40. Müllbacher, A., Regner, M., Wang, Y., Lee, E., Lobigs, M. & Simon, M. ( 2004; ). Can we really learn from model pathogens? Trends Immunol 25, 524–528.[CrossRef]
    [Google Scholar]
  41. Nagata, S. ( 1997; ). Apoptosis by death factor. Cell 88, 355–365.[CrossRef]
    [Google Scholar]
  42. Nansen, A., Jensen, T., Christensen, J. P., Andreasen, S. Ø., Röpke, C., Marker, O. & Thomsen, A. R. ( 1999; ). Compromised virus control and augmented perforin-mediated immunopathology in IFN-γ-deficient mice infected with lymphocytic choriomeningitis virus. J Immunol 163, 6114–6122.
    [Google Scholar]
  43. Ou, R., Zhou, S., Huang, L. & Moskophidis, D. ( 2001; ). Critical role for alpha/beta and gamma interferons in persistence of lymphocytic choriomeningitis virus by clonal exhaustion of cytotoxic T cells. J Virol 75, 8407–8423.[CrossRef]
    [Google Scholar]
  44. Parra, B., Hinton, D. R., Marten, N. W., Bergmann, C. C., Lin, M. T., Yang, C. S. & Stohlman, S. A. ( 1999; ). IFN-γ is required for viral clearance from central nervous system oligodendroglia. J Immunol 162, 1641–1647.
    [Google Scholar]
  45. Podack, E. R., Hengartner, H. & Lichtenheld, M. G. ( 1991; ). A central role of perforin in cytolysis? Annu Rev Immunol 9, 129–157.[CrossRef]
    [Google Scholar]
  46. Ramshaw, I. A., Ramsay, A. J., Karupiah, G., Rolph, M. S., Mahalingam, S. & Ruby, J. C. ( 1997; ). Cytokines and immunity to viral infections. Immunol Rev 159, 119–135.[CrossRef]
    [Google Scholar]
  47. Refaeli, Y., Van Parijs, L., Alexander, S. I. & Abbas, A. K. ( 2002; ). Interferon γ is required for activation-induced death of T lymphocytes. J Exp Med 196, 999–1005.[CrossRef]
    [Google Scholar]
  48. Regner, M., Müllbacher, A., Blanden, R. V. & Lobigs, M. ( 2001; ). Immunogenicity of two peptide determinants in the cytolytic T-cell response to flavivirus infection: inverse correlation between peptide affinity for MHC class I and T-cell precursor frequency. Viral Immunol 14, 135–149.[CrossRef]
    [Google Scholar]
  49. Rouvier, E., Luciani, M.-F. & Golstein, P. ( 1993; ). Fas involvement in Ca2+-independent T cell-mediated cytotoxicity. J Exp Med 177, 195–200.[CrossRef]
    [Google Scholar]
  50. Sarawar, S. R., Cardin, R. D., Brooks, J. W., Mehrpooya, M., Hamilton-Easton, A.-M., Mo, X. Y. & Doherty, P. C. ( 1997; ). Gamma interferon is not essential for recovery from acute infection with murine gammaherpesvirus 68. J Virol 71, 3916–3921.
    [Google Scholar]
  51. Scherret, J. H., Mackenzie, J. S., Hall, R. A., Deubel, V. & Gould, E. A. ( 2002; ). Phylogeny and molecular epidemiology of West Nile and Kunjin viruses. Curr Top Microbiol Immunol 267, 373–390.
    [Google Scholar]
  52. Shrestha, B. & Diamond, M. S. ( 2004; ). Role of CD8+ T cells in control of West Nile virus infection. J Virol 78, 8312–8321.[CrossRef]
    [Google Scholar]
  53. Shrestha, B., Samuel, M. A. & Diamond, M. S. ( 2006a; ). CD8+ T cells require perforin to clear West Nile virus from infected neurons. J Virol 80, 119–129.[CrossRef]
    [Google Scholar]
  54. Shrestha, B., Wang, T., Samuel, M. A., Whitby, K., Craft, J., Fikrig, E. & Diamond, M. S. ( 2006b; ). Gamma interferon plays a crucial early antiviral role in protection against West Nile virus infection. J Virol 80, 5338–5348.[CrossRef]
    [Google Scholar]
  55. Smithburn, K. C., Hughes, T. P., Burke, A. W. & Paul, J. H. ( 1940; ). A neurotropic virus isolated from the blood of a native of Uganda. Am J Trop Med Hyg 20, 471–492.
    [Google Scholar]
  56. Sobek, V., Balkow, S., Körner, H. & Simon, M. M. ( 2002; ). Antigen-induced cell death of T effector cells in vitro proceeds via the Fas pathway, requires endogenous interferon-γ and is independent of perforin and granzymes. Eur J Immunol 32, 2490–2499.[CrossRef]
    [Google Scholar]
  57. Taswell, C. ( 1981; ). Limiting dilution assays for the determination of immunocompetent cell frequencies. I. Data analysis. J Immunol 126, 1614–1619.
    [Google Scholar]
  58. Vassalli, P. ( 1992; ). The pathophysiology of tumor necrosis factors. Annu Rev Immunol 10, 411–452.[CrossRef]
    [Google Scholar]
  59. Wang, T., Scully, E., Yin, Z. & 7 other authors ( 2003a; ). IFN-γ-producing γδ T cells help control murine West Nile virus infection. J Immunol 171, 2524–2531.[CrossRef]
    [Google Scholar]
  60. Wang, Y., Lobigs, M., Lee, E. & Müllbacher, A. ( 2003b; ). CD8+ T cells mediate recovery and immunopathology in West Nile virus encephalitis. J Virol 77, 13323–13334.[CrossRef]
    [Google Scholar]
  61. Wang, Y., Lobigs, M., Lee, E. & Müllbacher, A. ( 2004; ). Exocytosis and Fas mediated cytolytic mechanisms exert protection from West Nile virus induced encephalitis in mice. Immunol Cell Biol 82, 170–173.[CrossRef]
    [Google Scholar]
  62. Weiner, L. P., Cole, G. A. & Nathanson, N. ( 1970; ). Experimental encephalitis following peripheral inoculation of West Nile virus in mice of different ages. J Hyg (Lond) 68, 435–446.[CrossRef]
    [Google Scholar]
  63. Wheelock, E. F. ( 1965; ). Interferon-like virus-inhibitor induced in human leukocytes by phytohemagglutinin. Science 149, 310–311.[CrossRef]
    [Google Scholar]
  64. Wong, G. H. W. & Goeddel, D. V. ( 1986; ). Tumour necrosis factors α and β inhibit virus replication and synergize with interferons. Nature 323, 819–822.[CrossRef]
    [Google Scholar]
  65. Yang, Y., Xiang, Z., Ertl, H. C. J. & Wilson, J. M. ( 1995; ). Upregulation of class I major histocompatibility complex antigens by interferon γ is necessary for T-cell-mediated elimination of recombinant adenovirus-infected hepatocytes in vivo. Proc Natl Acad Sci U S A 92, 7257–7261.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.81306-0
Loading
/content/journal/jgv/10.1099/vir.0.81306-0
Loading

Data & Media loading...

Most Cited This Month

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