Sustained inflammation and differential expression of interferons type I and III in PVM-infected interferon-gamma (IFNγ) gene-deleted mice

Stephanie F. Glineur, Aaron B. Bowen, Caroline M. Percopo, Katia E. Garcia-Crespo, Kimberly D. Dyer, Sergei I. Ochkur, Nancy A. Lee, James J. Lee, Joseph B. Domachowske, Helene F. Rosenberg

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Interferon gamma (IFNγ) has complex immunomodulatory and antiviral properties. While IFNγ is detected in the airways in response to infection with the pneumovirus pathogen, pneumonia virus of mice (PVM; Family Paramyxoviridae), its role in promoting disease has not been fully explored. Here, we evaluate PVM infection in IFNγ-/- mice. Although the IFNγ gene-deletion has no impact on weight loss, survival or virus kinetics, expression of IFNβ, IFNλ2/3 and IFN-stimulated 2-5' oligoadenylate synthetases was significantly diminished compared to wild-type counterparts. Furthermore, PVM infection in IFNγ-/- mice promoted prominent inflammation, including eosinophil and neutrophil infiltration into the airways and lung parenchyma, observed several days after peak virus titer. Potential mechanisms include over-production of chemoattractant and eosinophil-active cytokines (CXCL1, CCL11, CCL3 and IL5) in PVM-infected IFNγ-/- mice; likewise, IFNγ actively antagonized IL5-dependent eosinophil survival ex vivo. Our results may have clinical implications for pneumovirus infection in individuals with IFNγ signaling defects.

Original languageEnglish (US)
Pages (from-to)140-149
Number of pages10
JournalVirology
Volume468-470
DOIs
StatePublished - Nov 2014

Keywords

  • Eosinophils
  • Inflammation
  • Interferon
  • Pneumovirus

ASJC Scopus subject areas

  • Virology

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    Glineur, S. F., Bowen, A. B., Percopo, C. M., Garcia-Crespo, K. E., Dyer, K. D., Ochkur, S. I., Lee, N. A., Lee, J. J., Domachowske, J. B., & Rosenberg, H. F. (2014). Sustained inflammation and differential expression of interferons type I and III in PVM-infected interferon-gamma (IFNγ) gene-deleted mice. Virology, 468-470, 140-149. https://doi.org/10.1016/j.virol.2014.07.039