1887

Abstract

Human interferon lambdas (IFN-s) (type III IFNs) exhibit antiviral activity by binding to a receptor complex distinct from that used by type I and type II IFNs, and subsequent signalling through the Janus kinase signal transducers and activators of transcription (STAT) pathway. However, evidence for a function of type III IFNs during virus infection is lacking. Here, the expression of murine IFN-s by recombinant vaccinia virus (VACV) is described and these proteins are shown to have potent antiviral activity . VACV expressing murine IFN-2 (vIFN-2) and IFN-3 (vIFN-3) showed normal growth in tissue culture and expressed -glycosylated IFN- in infected cell extracts and culture supernatants. The role that murine IFN-s play during virus infection was assessed in two different mouse models. vIFN-2 and vIFN-3 were avirulent for mice infected intranasally and induced no signs of illness or weight loss, in contrast to control viruses. Attenuation of vIFN-2 was associated with increases in lymphocytes in bronchial alveolar lavages and CD4 T cells in total-lung lymphocyte preparations. In addition, vIFN-2 was cleared more rapidly from infected lungs and, in contrast to control viruses, did not disseminate to the brain. Expression of IFN-2 also attenuated VACV in an intradermal-infection model, characterized by a delay in lesion onset and reduced lesion size. Thus, by characterizing murine IFN-s within a mouse infection model, the potent antiviral and immunostimulatory activity of IFN-s in response to poxvirus infection has been demonstrated.

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2005-06-01
2020-07-11
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References

  1. Alcami A., Smith G. L. 1992; A soluble receptor for interleukin-1 β encoded by vaccinia virus: a novel mechanism of virus modulation of the host response to infection. Cell 71:153–167 [CrossRef]
    [Google Scholar]
  2. Alcamí A., Smith G. L. 1995; Vaccinia, cowpox, and camelpox viruses encode soluble gamma interferon receptors with novel broad species specificity. J Virol 69:4633–4639
    [Google Scholar]
  3. Bartlett N. W., Dumoutier L., Renauld J.-C., Kotenko S. V., McVey C. E., Lee H.-J., Smith G. L. 2004; A new member of the interleukin 10-related cytokine family encoded by a poxvirus. J Gen Virol 85:1401–1412 [CrossRef]
    [Google Scholar]
  4. Boyle D. B., Coupar B. E. 1988; A dominant selectable marker for the construction of recombinant poxviruses. Gene 65:123–128 [CrossRef]
    [Google Scholar]
  5. Darnell J. E. Jr, Kerr I. M., Stark G. R. 1994; Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 264:1415–1421 [CrossRef]
    [Google Scholar]
  6. Dumoutier L., Tounsi A., Michiels T., Sommereyns C., Kotenko S. V., Renauld J.-C. 2004; Role of the interleukin (IL)-28 receptor tyrosine residues for antiviral and antiproliferative activity of IL-29/interferon- λ 1: similarities with type I interferon signaling. J Biol Chem 279:32269–32274 [CrossRef]
    [Google Scholar]
  7. Falkner F. G., Moss B. 1990; Transient dominant selection of recombinant vaccinia viruses. J Virol 64:3108–3111
    [Google Scholar]
  8. Goldman L. A., Cutrone E. C., Kotenko S. V., Krause C. D., Langer J. A. 1996; Modifications of vectors pEF-BOS, pcDNA1 and pcDNA3 result in improved convenience and expression. Biotechniques 21:1013–1015
    [Google Scholar]
  9. Hussell T., Khan U., Openshaw P. 1997; IL-12 treatment attenuates T helper cell type 2 and B cell responses but does not improve vaccine-enhanced lung illness. J Immunol 159:328–334
    [Google Scholar]
  10. Kotenko S. V., Langer J. A. 2004; Full house: 12 receptors for 27 cytokines. Int Immunopharmacol 4:593–608 [CrossRef]
    [Google Scholar]
  11. Kotenko S. V., Saccani S., Izotova L. S., Mirochnitchenko O. V., Pestka S. 2000; Human cytomegalovirus harbors its own unique IL-10 homolog (cmvIL-10). Proc Natl Acad Sci U S A 97:1695–1700 [CrossRef]
    [Google Scholar]
  12. Kotenko S. V., Gallagher G., Baurin V. V. 7 other authors 2003; IFN- λ s mediate antiviral protection through a distinct class II cytokine receptor complex. Nat Immunol 4:69–77
    [Google Scholar]
  13. Lane J. M., Ruben F. L., Neff J. M., Millar J. D. 1969; Complications of smallpox vaccination, 1968. N Engl J Med 281:1201–1208 [CrossRef]
    [Google Scholar]
  14. Lindell D. M., Standiford T. J., Mancuso P., Leshen Z. J., Huffnagle G. B. 2001; Macrophage inflammatory protein 1 α /CCL3 is required for clearance of an acute Klebsiella pneumoniae pulmonary infection. Infect Immun 69:6364–6369 [CrossRef]
    [Google Scholar]
  15. Malmgaard L. 2004; Induction and regulation of IFNs during viral infections. J Interferon Cytokine Res 24:439–454 [CrossRef]
    [Google Scholar]
  16. Pestka S. 1997; The interferon receptors. Semin Oncol 24:S9-18–S19-40
    [Google Scholar]
  17. Pestka S., Krause C. D., Walter M. R. 2004; Interferons, interferon-like cytokines, and their receptors. Immunol Rev 202:8–32 [CrossRef]
    [Google Scholar]
  18. Ramshaw I., Ruby J., Ramsay A., Ada G., Karupiah G. 1992; Expression of cytokines by recombinant vaccinia viruses: a model for studying cytokines in virus infections in vivo. Immunol Rev 127:157–182 [CrossRef]
    [Google Scholar]
  19. Reading P. C., Smith G. L. 2003; A kinetic analysis of immune mediators in the lungs of mice infected with vaccinia virus and comparison with intradermal infection. J Gen Virol 84:1973–1983 [CrossRef]
    [Google Scholar]
  20. Sheppard P., Kindsvogel W., Xu W. 23 other authors 2003; IL-28, IL-29 and their class II cytokine receptor IL-28R. Nat Immunol 4:63–68 [CrossRef]
    [Google Scholar]
  21. Symons J. A., Tscharke D. C., Price N., Smith G. L. 2002; A study of the vaccinia virus interferon- γ receptor and its contribution to virus virulence. J Gen Virol 83:1953–1964
    [Google Scholar]
  22. Tscharke D. C., Smith G. L. 1999; A model for vaccinia virus pathogenesis and immunity based on intradermal injection of mouse ear pinnae. J Gen Virol 80:2751–2755
    [Google Scholar]
  23. Tscharke D. C., Reading P. C., Smith G. L. 2002; Dermal infection with vaccinia virus reveals roles for virus proteins not seen using other inoculation routes. J Gen Virol 83:1977–1986
    [Google Scholar]
  24. Wilcock D., Smith G. L. 1994; Vaccinia virus core protein VP8 is required for virus infectivity, but not for core protein processing or for INV and EEV formation. Virology 202:294–304 [CrossRef]
    [Google Scholar]
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