1887

Abstract

The early inflammatory response to a virus may be critical in restricting infection and in shaping the subsequent adaptive immune response. In this study we have examined the early inflammatory response of mice following infection with vaccinia virus (VV) strain Western Reserve (WR). Respiratory challenge of BALB/c mice with VV led to early virus replication in the lung and upper respiratory tract followed by dissemination of virus to other visceral organs and to the brain. The number of inflammatory cells, largely macrophages and T lymphocytes, recovered from bronchoalveolar lavage (BAL) fluid increased markedly during infection and coincided with the expression of CC chemokine ligands (CCL) 3, 2 and 11 and CXC chemokine ligands (CXCL) 1 and 2/3 in BAL. The peak of the inflammatory response occurred around day 10 and declined thereafter. The antiviral cytokines IFN- and TNF-, and the reactive nitrogen intermediate nitric oxide (NO), were also detected in BAL from VV-infected mice. A markedly different inflammatory response was observed after intradermal inoculation of WR into the ear pinnae of mice. Intradermal challenge was followed by highly localized virus replication and by a cellular influx, consisting largely of neutrophils and T lymphocytes, into the dermal compartment of the infected ear. Together these findings highlight differences in the pathogenesis and in the cellular inflammatory response to WR following intranasal and intradermal inoculation of mice.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.19285-0
2003-08-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/84/8/vir841973.html?itemId=/content/journal/jgv/10.1099/vir.0.19285-0&mimeType=html&fmt=ahah

References

  1. Alcamí A., Smith G. L. 1992; A soluble receptor for interleukin-1 beta encoded by vaccinia virus: a novel mechanism of virus modulation of the host response to infection. Cell 71:153–167
    [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. Alcamí A., Koszinowski U. H. 2000; Viral mechanisms of immune evasion. Trends Microbiol 8:410–418
    [Google Scholar]
  4. Alcamí A., Khanna A., Paul N. L., Smith G. L. 1999; Vaccinia virus strains Lister, USSR and Evans express soluble and cell surface tumour necrosis factors receptor. J Gen Virol 80:949–959
    [Google Scholar]
  5. Baggiolini M. 1998; Chemokines and leukocyte traffic. Nature 392:565–568
    [Google Scholar]
  6. Baxby D. 1981 Jenner's Smallpox Vaccine. The Riddle of the Origin of Vaccinia Virus London: Heinemann;
    [Google Scholar]
  7. Belkaid Y., Jouin H., Milon G. 1996; A method to recover, enumerate and identify lymphomyeloid cells present in an inflammatory dermal site: a study in laboratory mice. J Immunol Methods 199:5–25
    [Google Scholar]
  8. Belkaid Y., Kamhawi S., Modi G., Valenzuela J., Noben-Trauth N., Rowton E., Ribeiro J., Sacks D. L. 1998; Development of a natural model of cutaneous leishmaniasis: powerful effects of vector saliva and saliva preexposure on the long-term outcome of Leishmania major infection in the mouse ear dermis. J Exp Med 188:1941–1953
    [Google Scholar]
  9. Bronson L. H., Parker R. F. 1941; The neutralization of vaccine virus by immune serum: titration by the intracerebral inoculation of mice. J Bacteriol 41:56–57
    [Google Scholar]
  10. Buller R. M., Smith G. L., Cremer K., Notkins A. L., Moss B. 1985; Decreased virulence of recombinant vaccinia virus expression vectors is associated with a thymidine kinase-negative phenotype. Nature 317:813–815
    [Google Scholar]
  11. Carr M. W., Roth S. J., Luther E., Rose S. S., Springer T. A. 1994; Monocyte chemoattractant protein 1 acts as a T-lymphocyte chemoattractant. Proc Natl Acad Sci U S A 91:3652–3656
    [Google Scholar]
  12. 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-gamma genes. Science 259:1739–1742
    [Google Scholar]
  13. Ding A. H., Nathan C. F., Stuehr D. J. 1988; Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. Comparison of activating cytokines and evidence for independent production. J Immunol 141:2407–2412
    [Google Scholar]
  14. Fenner F., Wittek R., Dumbell K. R. 1989 The Orthopoxviruses London: Academic Press;
    [Google Scholar]
  15. Haeberle H. A., Kuziel W. A., Dieterich H. J., Casola A., Gatalica Z., Garofalo R. P. 2001; Inducible expression of inflammatory chemokines in respiratory syncytial virus-infected mice: role of MIP-1 α in lung pathology. J Virol 75:878–890
    [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-gamma receptor. Science 259:1742–1745
    [Google Scholar]
  17. Karupiah G., Harris N. 1995; Inhibition of viral replication by nitric oxide and its reversal by ferrous sulfate and tricarboxylic acid cycle metabolites. J Exp Med 181:2171–2179
    [Google Scholar]
  18. Karupiah G., Blanden R. V., Ramshaw I. A. 1990; Interferon- γ is involved in the recovery of athymic nude mice from recombinant vaccinia virus/interleukin 2 infection. J Exp Med 172:1495–1503
    [Google Scholar]
  19. Lee M. S., Roos J. M., McGuigan L. C., Smith K. A., Cormier L., Cohen K., Roberts B. E., Payne L. G. 1992; Molecular attenuation of vaccinia virus: mutant generation and animal characterization. J Virol 66:2617–2630
    [Google Scholar]
  20. Mackett M., Smith G. L., Moss B. 1985; The construction and characterization of vaccinia virus recombinants expressing foreign genes. In DNA Cloning: a Practical Approach pp  191–211 Edited by Glover D. M. Oxford: IRL Press;
    [Google Scholar]
  21. Melkova Z., Esteban M. 1994; Interferon-gamma severely inhibits DNA synthesis of vaccinia virus in a macrophage cell line. Virology 198:731–735
    [Google Scholar]
  22. Miyazato A., Kawakami K., Iwakura Y., Saito A. 2000; Chemokine synthesis and cellular inflammatory changes in lungs of mice bearing p40tax of human T-lymphotropic virus type 1. Clin Exp Immunol 120:113–124
    [Google Scholar]
  23. Mossman K., Upton C., Buller R. M., McFadden G. 1995; Species specificity of ectromelia virus and vaccinia virus interferon-gamma binding proteins. Virology 208:762–769
    [Google Scholar]
  24. Reading P. C., Khanna A., Smith G. L. 2002; Vaccinia virus CrmE encodes a soluble and cell surface tumor necrosis factor receptor that contributes to virus virulence. Virology 292:285–298
    [Google Scholar]
  25. Reading P. C., Symons J. A., Smith G. L. 2003; A soluble chemokine-binding protein from vaccinia virus reduces virulence and the inflammatory response to infection. J Immunol 170:1435–1442
    [Google Scholar]
  26. Rollins B. J., Yoshimura T., Leonard E. J., Pober J. S. 1990; Cytokine-activated human endothelial cells synthesize and secrete a monocyte chemoattractant, MCP-1/JE. Am J Pathol 136:1229–1233
    [Google Scholar]
  27. Rolph M. S., Cowden W. B., Medveczky C. J., Ramshaw I. A. 1996; A recombinant vaccinia virus encoding inducible nitric oxide synthase is attenuated in vivo. J Virol 70:7678–7685
    [Google Scholar]
  28. Rossi D., Zlotnik A. 2000; The biology of chemokines and their receptors. Annu Rev Immunol 18:217–242
    [Google Scholar]
  29. Ruby J., Ramshaw I. 1991; The antiviral activity of immune CD8+ T cells is dependent on interferon-gamma. Lymphokine Cytokine Res 10:353–358
    [Google Scholar]
  30. Sarawar S. R., Lee B. J., Anderson M., Teng Y. C., Zuberi R., Von Gesjen S. 2002; Chemokine induction and leukocyte trafficking to the lungs during murine gammaherpesvirus 68 (MHV-68) infection. Virology 293:54–62
    [Google Scholar]
  31. Sarmiento M., Glasebrook A. L., Fitch F. W. 1980; IgG or IgM monoclonal antibodies reactive with different determinants on the molecular complex bearing Lyt 2 antigen block T cell-mediated cytolysis in the absence of complement. J Immunol 125:2665–2672
    [Google Scholar]
  32. Schall T. J., Bacon K., Camp R. D., Kaspari J. W., Goeddel D. V. 1993; Human macrophage inflammatory protein alpha (MIP-1 alpha) and MIP-1 beta chemokines attract distinct populations of lymphocytes. J Exp Med 177:1821–1826
    [Google Scholar]
  33. Selin L. K., Santolucito P. A., Pinto A. K., Szomolanyi-Tsuda E., Welsh R. M. 2001; Innate immunity to viruses: control of vaccinia virus infection by gamma delta T cells. J Immunol 166:6784–6794
    [Google Scholar]
  34. Smith G. L. 2000; Secreted poxvirus proteins that interact with the immune system. In Effects of Microbes on the Immune System pp  491–507 Edited by Cunningham M. W., Fujinami R. S. Philadelphia: Lippincott Williams & Wilkins;
    [Google Scholar]
  35. Smith V. P., Bryant N. A., Alcamí A. 2000; Ectromelia, vaccinia and cowpox viruses encode secreted interleukin-18- binding proteins. J Gen Virol 81:1223–1230
    [Google Scholar]
  36. Symons J. A., Tscharke D. C., Price N., Smith G. L. 2002a; A study of the vaccinia virus interferon- γ receptor and its contribution to virus virulence. J Gen Virol 83:1953–1964
    [Google Scholar]
  37. Symons J. A., Adams E., Tscharke D. C., Reading P. C., Waldmann H., Smith G. L. 2002b; The vaccinia virus C12L protein inhibits mouse IL-18 and promotes virulence in a mouse intranasal model. J Gen Virol 83:2833–2844
    [Google Scholar]
  38. Takanami-Ohnishi Y., Amano S., Kimura S., Asada S., Utani A., Maruyama M., Osada H., Tsunoda H., Irukayama-Tomobe Y., Goto K., Karin M., Sudo T., Kasuya Y. 2002; Essential role of p38 mitogen-activated protein kinase in contact hypersensitivity. J Biol Chem 277:37896–37903
    [Google Scholar]
  39. Tripp R. A., Jones L., Anderson L. J. 2000; Respiratory syncytial virus G and/or SH glycoproteins modify CC and CXC chemokine mRNA expression in the BALB/c mouse. J Virol 74:6227–6229
    [Google Scholar]
  40. 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]
  41. 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]
  42. Turner G. S. 1967; Respiratory infection of mice with vaccinia virus. J Gen Virol 1:399–402
    [Google Scholar]
  43. Weinberg J. B., Lutzke M. L., Efstathiou S., Kunkel S. L., Rochford R. 2002; Elevated chemokine responses are maintained in lungs after clearance of viral infection. J Virol 76:10518–10523
    [Google Scholar]
  44. Williamson J. D., Reith R. W., Jeffrey L. J., Arrand J. R., Mackett M. 1990; Biological characterization of recombinant vaccinia viruses in mice infected by the respiratory route. J Gen Virol 71:2761–2767
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.19285-0
Loading
/content/journal/jgv/10.1099/vir.0.19285-0
Loading

Data & Media loading...

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