TY - JOUR
T1 - Sustained inflammation and differential expression of interferons type I and III in PVM-infected interferon-gamma (IFNγ) gene-deleted mice
AU - Glineur, Stephanie F.
AU - Bowen, Aaron B.
AU - Percopo, Caroline M.
AU - Garcia-Crespo, Katia E.
AU - Dyer, Kimberly D.
AU - Ochkur, Sergei I.
AU - Lee, Nancy A.
AU - Lee, James J.
AU - Domachowske, Joseph B.
AU - Rosenberg, Helene F.
N1 - Funding Information:
Work supported by NIAID Division of Intramural Research funding ( AI000943 to HFR) the Huynen Foundation (University of Liège, Belgium) and the Rotary Foundation , Rotary International (to SFG).
PY - 2014/11
Y1 - 2014/11
N2 - 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.
AB - 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.
KW - Eosinophils
KW - Inflammation
KW - Interferon
KW - Pneumovirus
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U2 - 10.1016/j.virol.2014.07.039
DO - 10.1016/j.virol.2014.07.039
M3 - Article
C2 - 25173090
AN - SCOPUS:84906772363
SN - 0042-6822
VL - 468-470
SP - 140
EP - 149
JO - Virology
JF - Virology
ER -