Related Experiment Video
Updated: Apr 25, 2026
Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
Sustained inflammation and differential expression of interferons type I and III in PVM-infected interferon-gamma
Stephanie F Glineur1, Aaron B Bowen1, Caroline M Percopo1
1Inflammation Immunobiology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
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.
Insights
Interferon gamma (IFNγ) deficiency in mice infected with pneumonia virus of mice (PVM) did not affect viral load but increased airway inflammation. This suggests IFNγ plays a protective role against PVM-induced immunopathology.
Area of Science:
- Immunology
- Virology
- Respiratory Medicine
Background:
- Interferon gamma (IFNγ) exhibits complex immunomodulatory and antiviral functions.
- IFNγ is present in airways during pneumovirus infections, but its role in disease pathogenesis is not fully understood.
Purpose of the Study:
- To investigate the role of IFNγ in the host response to pneumonia virus of mice (PVM) infection.
- To evaluate the impact of IFNγ deficiency on disease severity, viral kinetics, and inflammatory responses during PVM infection.
Main Methods:
- Pneumonia virus of mice (PVM) infection was studied in wild-type and IFNγ gene-deleted (IFNγ(-/-)) mice.
- Measurements included weight loss, survival, virus titers, and expression of interferon-stimulated genes.
- Analysis of airway inflammation, including immune cell infiltration and cytokine profiles, was performed.
Main Results:
- IFNγ gene deletion did not alter weight loss, survival rates, or PVM viral kinetics.
- IFNγ deficiency led to significantly diminished expression of IFNβ, IFNλ2/3, and IFN-stimulated genes.
- PVM infection in IFNγ(-/-) mice resulted in prominent airway inflammation, characterized by eosinophil and neutrophil infiltration, and elevated levels of chemoattractant cytokines (CXCL1, CCL11, CCL3, IL5).
- Ex vivo studies demonstrated that IFNγ antagonizes IL5-dependent eosinophil survival.
Conclusions:
- IFNγ is not essential for controlling PVM replication or acute disease but plays a critical role in modulating the inflammatory response.
- Lack of IFNγ signaling exacerbates PVM-induced airway inflammation, potentially through increased production of eosinophil-active cytokines.
- These findings highlight the complex role of IFNγ in viral infections and may have implications for pneumovirus infections in individuals with IFNγ pathway defects.
Related Concept Videos
01:16In-vitro Mutagenesis
02:43Mouse Models of Cancer Study
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...