1887

Abstract

Respiratory syncytial virus (RSV) is the primary cause of bronchiolitis in young children. In general, RSV is considered to be a poor inducer of type I (alpha/beta) interferons (IFNs). Measurement of active type I IFN production during infection is demanding, as multiple IFN subtypes with overlapping activities are produced. In contrast, Mx gene expression, which is tightly regulated by type I IFN expression, is easily determined. This study therefore measured Mx expression as a reliable surrogate marker of type I IFN activity during RSV infection in a cotton rat model. It was shown that expression of Mx genes was dramatically augmented in the lungs of infected animals in a dose- and virus strain-dependent manner. The expression of Mx genes in the lungs was paralleled by their induction in the nose and spleen, although in spleen no simultaneous virus gene expression was detected. Reinfection of RSV-immune animals leads to abortive virus replication in the lungs. Thus, type I IFN and Mx gene expression was triggered in reinfected animals, even though virus could not be isolated from their lungs. Furthermore, it was demonstrated that immunity to RSV wanes with time. Virus replication and Mx gene expression became more prominent with increasing intervals between primary infection and reinfection. These results highlight the role of type I IFN in modulation of the immune response to RSV.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.83294-0
2008-01-01
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/jgv/89/1/261.html?itemId=/content/journal/jgv/10.1099/vir.0.83294-0&mimeType=html&fmt=ahah

References

  1. Blanco J. C., Richardson J. Y., Darnell M. E., Rowzee A., Pletneva L., Porter D. D., Prince G. A. 2002; Cytokine and chemokine gene expression after primary and secondary respiratory syncytial virus infection in cotton rats. J Infect Dis 185:1780–1785 [CrossRef]
    [Google Scholar]
  2. Bossert B., Marozin S., Conzelmann K. K. 2003; Nonstructural proteins NS1 and NS2 of bovine respiratory syncytial virus block activation of interferon regulatory factor 3. J Virol 77:8661–8668 [CrossRef]
    [Google Scholar]
  3. Boukhvalova M. S., Prince G. A., Soroush L., Harrigan D. C., Vogel S. N., Blanco J. C. 2006; The TLR4 agonist, monophosphoryl lipid A, attenuates the cytokine storm associated with respiratory syncytial virus vaccine-enhanced disease. Vaccine 24:5027–5035 [CrossRef]
    [Google Scholar]
  4. Boukhvalova M. S., Prince G. A., Blanco J. C. G. 2007; Respiratory syncytial virus infects and abortively replicates in the lungs in spite of pre-existing immunity. J Virol 81:9443–9450 [CrossRef]
    [Google Scholar]
  5. Bracci L., Canini I., Venditti M., Spada M., Puzelli S., Donatelli I., Belardelli F., Proietti E. 2006; Type I IFN as a vaccine adjuvant for both systemic and mucosal vaccination against influenza virus. Vaccine 24:Suppl. 2S56–S57 [CrossRef]
    [Google Scholar]
  6. Chonmaitree T., Roberts N. J. Jr, Douglas R. G. Jr, Hall C. B., Simons R. L. 1981; Interferon production by human mononuclear leukocytes: differences between respiratory syncytial virus and influenza viruses. Infect Immun 32:300–303
    [Google Scholar]
  7. Diaz M. O., Pomykala H. M., Bohlander S. K., Maltepe E., Malik K., Brownstein B., Olopade O. I. 1994; Structure of the human type-I interferon gene cluster determined from a YAC clone contig. Genomics 22:540–552 [CrossRef]
    [Google Scholar]
  8. Durbin J. E., Johnson T. R., Durbin R. K., Mertz S. E., Morotti R. A., Peebles R. S., Graham B. S. 2002; The role of IFN in respiratory syncytial virus pathogenesis. J Immunol 168:2944–2952 [CrossRef]
    [Google Scholar]
  9. Falsey A. R., Hennessey P. A., Formica M. A., Cox C., Walsh E. E. 2005; Respiratory syncytial virus infection in elderly and high-risk adults. N Engl J Med 352:1749–1759 [CrossRef]
    [Google Scholar]
  10. Flohr F., Schneider-Schaulies S., Haller O., Kochs G. 1999; The central interactive region of human MxA GTPase is involved in GTPase activation and interaction with viral target structures. FEBS Lett 463:24–28 [CrossRef]
    [Google Scholar]
  11. Forster J., Schweizer M., Schumacher R. F., Kaufmehl K., Lob S. 1996; MxA protein in infants and children with respiratory tract infection. Acta Paediatr 85:163–167 [CrossRef]
    [Google Scholar]
  12. Garofalo R., Mei F., Espejo R., Ye G., Haeberle H., Baron S., Ogra P. L., Reyes V. E. 1996; Respiratory syncytial virus infection of human respiratory epithelial cells up-regulates class I MHC expression through the induction of IFN- β and IL-1 α . J Immunol 157:2506–2513
    [Google Scholar]
  13. Guerrero-Plata A., Casola A., Suarez G., Yu X., Spetch L., Peeples M. E., Garofalo R. P. 2006; Differential response of dendritic cells to human metapneumovirus and respiratory syncytial virus. Am J Respir Cell Mol Biol 34:320–329 [CrossRef]
    [Google Scholar]
  14. Hall C. B., Douglas R. G. Jr, Simons R. L., Geiman J. M. 1978; Interferon production in children with respiratory syncytial, influenza, and parainfluenza virus infections. J Pediatr 93:28–32 [CrossRef]
    [Google Scholar]
  15. Hall C. B., Douglas R. G. Jr, Simons R. L. 1981; Interferon production in adults with respiratory syncytial viral infection. Ann Intern Med 94:53–55 [CrossRef]
    [Google Scholar]
  16. Halminen M., Ilonen J., Julkunen I., Ruuskanen O., Simell O., Makela M. J. 1997; Expression of MxA protein in blood lymphocytes discriminates between viral and bacterial infections in febrile children. Pediatr Res 41:647–650 [CrossRef]
    [Google Scholar]
  17. Henderson F. W., Collier A. M., Clyde W. A. Jr, Denny F. W. 1979; Respiratory-syncytial-virus infections, reinfections and immunity. A prospective, longitudinal study in young children. N Engl J Med 300:530–534 [CrossRef]
    [Google Scholar]
  18. Hiscott J., Cantell K., Weissmann C. 1984; Differential expression of human interferon genes. Nucleic Acids Res 12:3727–3746 [CrossRef]
    [Google Scholar]
  19. Holzinger D., Jorns C., Stertz S., Boisson-Dupuis S., Thimme R., Weidmann M., Casanova J.-L., Haller O., Kochs G. 2007; Induction of MxA gene expression by influenza A virus requires type I or type III interferon signaling. J Virol 81:7776–7785 [CrossRef]
    [Google Scholar]
  20. Hornung V., Schlender J., Guenthner-Biller M., Rothenfusser S., Endres S., Conzelmann K. K., Hartmann G. 2004; Replication-dependent potent IFN- α induction in human plasmacytoid dendritic cells by a single-stranded RNA virus. J Immunol 173:5935–5943 [CrossRef]
    [Google Scholar]
  21. Isaacs D. 1989; Production of interferon in respiratory syncytial virus bronchiolitis. Arch Dis Child 64:92–95 [CrossRef]
    [Google Scholar]
  22. Jamaluddin M., Wang S., Garofalo R. P., Elliott T., Casola A., Baron S., Brasier A. R. 2001; IFN- β mediates coordinate expression of antigen-processing genes in RSV-infected pulmonary epithelial cells. Am J Physiol Lung Cell Mol Physiol 280:L248–L257
    [Google Scholar]
  23. McIntosh K. 1978; Interferon in nasal secretions from infants with viral respiratory tract infections. J Pediatr 93:33–36 [CrossRef]
    [Google Scholar]
  24. Nakayama T., Sonoda S., Urano T., Sasaki K., Maehara N., Makino S. 1993; Detection of alpha-interferon in nasopharyngeal secretions and sera in children infected with respiratory syncytial virus. Pediatr Infect Dis J 12:925–929 [CrossRef]
    [Google Scholar]
  25. Pletneva L. M., Haller O., Porter D. D., Prince G. A., Blanco J. C. 2006; Interferon-inducible Mx gene expression in cotton rats: cloning, characterization, and expression during influenza viral infection. J Interferon Cytokine Res 26:914–921 [CrossRef]
    [Google Scholar]
  26. Prince G. A., Jenson A. B., Horswood R. L., Camargo E., Chanock R. M. 1978; The pathogenesis of respiratory syncytial virus infection in cotton rats. Am J Pathol 93:771–791
    [Google Scholar]
  27. Prince G. A., Prieels J. P., Slaoui M., Porter D. D. 1999; Pulmonary lesions in primary respiratory syncytial virus infection, reinfection, and vaccine-enhanced disease in the cotton rat ( Sigmodon hispidus . Lab Invest 79:1385–1392
    [Google Scholar]
  28. Prince G. A., Mond J. J., Porter D. D., Yim K. C., Lan S. J., Klinman D. M. 2003; Immunoprotective activity and safety of a respiratory syncytial virus vaccine: mucosal delivery of fusion glycoprotein with a CpG oligodeoxynucleotide adjuvant. J Virol 77:13156–13160 [CrossRef]
    [Google Scholar]
  29. Richter B. W., Onuska J. M., Niewiesk S., Prince G. A., Eichelberger M. C. 2005; Antigen-dependent proliferation and cytokine induction in respiratory syncytial virus-infected cotton rats reflect the presence of effector-memory T cells. Virology 337:102–110 [CrossRef]
    [Google Scholar]
  30. Roberts N. J., Hiscott J. Jr, Signs D. J. 1992; The limited role of the human interferon system response to respiratory syncytial virus challenge: analysis and comparison to influenza virus challenge. Microb Pathog 12:409–414 [CrossRef]
    [Google Scholar]
  31. Roers A., Hochkeppel H. K., Horisberger M. A., Hovanessian A., Haller O. 1994; MxA gene expression after live virus vaccination: a sensitive marker for endogenous type I interferon. J Infect Dis 169:807–813 [CrossRef]
    [Google Scholar]
  32. Schlender J., Hornung V., Finke S., Gunthner-Biller M., Marozin S., Brzozka K., Moghim S., Endres S., Hartmann G., Conzelmann K. K. 2005; Inhibition of Toll-like receptor 7- and 9-mediated alpha/beta interferon production in human plasmacytoid dendritic cells by respiratory syncytial virus and measles virus. J Virol 79:5507–5515 [CrossRef]
    [Google Scholar]
  33. Seya T., Akazawa T., Tsujita T., Matsumoto M. 2006; Role of Toll-like receptors in adjuvant-augmented immune therapies. Evid Based Complement Alternat Med 3:31–38 [CrossRef]
    [Google Scholar]
  34. Simon A., Fah J., Haller O., Staeheli P. 1991; Interferon-regulated Mx genes are not responsive to interleukin-1, tumor necrosis factor, and other cytokines. J Virol 65:968–971
    [Google Scholar]
  35. Smith P. L., Lombardi G., Foster G. R. 2005; Type I interferons and the innate immune response – more than just antiviral cytokines. Mol Immunol 42:869–877 [CrossRef]
    [Google Scholar]
  36. Spann K. M., Tran K. C., Chi B., Rabin R. L., Collins P. L. 2004; Suppression of the induction of alpha, beta, and lambda interferons by the NS1 and NS2 proteins of human respiratory syncytial virus in human epithelial cells and macrophages. J Virol 78:4363–4369 [CrossRef]
    [Google Scholar]
  37. Stark G. R., Kerr I. M., Williams B. R., Silverman R. H., Schreiber R. D. 1998; How cells respond to interferons. Annu Rev Biochem 67:227–264 [CrossRef]
    [Google Scholar]
  38. Stertz S., Dittmann J., Blanco J. C. G., Pletneva L. M., Haller O., Kochs G. 2007; The antiviral potential of interferon-induced cotton rat Mx proteins against orthomyxo- (influenza)-, rhabdo- and bunyaviruses. J Interferon Cytokine Res 27:847–856 [CrossRef]
    [Google Scholar]
  39. Taylor C. E., Webb M. S., Milner A. D., Milner P. D., Morgan L. A., Scott R., Stokes G. M., Swarbrick A. S., Toms G. L. 1989; Interferon alfa, infectious virus, and virus antigen secretion in respiratory syncytial virus infections of graded severity. Arch Dis Child 64:1656–1660 [CrossRef]
    [Google Scholar]
  40. Theofilopoulos A. N., Baccala R., Beutler B., Kono D. H. 2005; Type I interferons ( α / β ) in immunity and autoimmunity. Annu Rev Immunol 23:307–336 [CrossRef]
    [Google Scholar]
  41. Thompson W. W., Shay D. K., Weintraub E., Brammer L., Cox N., Anderson L. J., Fukuda K. 2003; Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA 289:179–186 [CrossRef]
    [Google Scholar]
  42. Tovey M. G., Lallemand C., Meritet J. F., Maury C. 2006; Adjuvant activity of interferon alpha: mechanism(s) of action. Vaccine 24:Suppl. 2S46–S47 [CrossRef]
    [Google Scholar]
  43. Wang H., Peters N., Schwarze J. 2006; Plasmacytoid dendritic cells limit viral replication, pulmonary inflammation, and airway hyperresponsiveness in respiratory syncytial virus infection. J Immunol 177:6263–6270 [CrossRef]
    [Google Scholar]
  44. Welliver R. C. 2003; Review of epidemiology and clinical risk factors for severe respiratory syncytial virus (RSV) infection. J Pediatr 143:S112–S117 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.83294-0
Loading
/content/journal/jgv/10.1099/vir.0.83294-0
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