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The pathogenesis of pneumonitis due to murine cytomegalovirus
Abstract:
Virus replication and interstitial pneumonia were studied in BALB/c mice inoculated intranasally with murine cytomegalovirus (MCMV). In normal mice MCMV replicated in lung tissue but did not produce any consistent histologic abnormalities through day 21. The addition of a single dose of cyclophosphamide (0.20 mg/g) 24 hr after virus inoculation resulted in a slight increase in lung virus titers on day 10. No histologic abnormalities were noted before day 10. However, 22 or 32 virus-infected mice treated with a single dose of cyclophosphamide but only two of 26 simultaneously mock-infected, cyclophosphamide-treated mice developed severe interstitial pneumonia 10-14 days after inoculation. In contrast, animals given cyclophosphamide (0.05 mg/g) every five days after the initial dose developed a 10-fold increase in lung virus titer, but interstitial pneumonia was not observed. These data suggest that the interstitial pneumonitis seen with MCMV pulmonary infection may be immunologically mediated rather than the result of direct viral damage to the lung.
Insights
Murine cytomegalovirus (MCMV) infection in mice caused lung virus replication but not pneumonia. Immunosuppression with cyclophosphamide led to severe interstitial pneumonia, suggesting an immune-mediated response.
Area of Science:
- Immunology
- Virology
- Pathology
Background:
- Murine cytomegalovirus (MCMV) is a common viral pathogen in mice.
- Pulmonary MCMV infection can lead to interstitial pneumonia.
- The mechanisms underlying MCMV-induced pneumonia are not fully understood.
Purpose of the Study:
- To investigate the role of the immune system in MCMV-induced interstitial pneumonia.
- To determine if immunosuppression exacerbates MCMV lung pathology.
Main Methods:
- BALB/c mice were inoculated intranasally with MCMV.
- Mice received single or multiple doses of cyclophosphamide, an immunosuppressant.
- Lung virus titers and histopathology were assessed at various time points.
Main Results:
- MCMV replicated in the lungs of normal mice without causing significant pathology.
- A single dose of cyclophosphamide post-infection led to severe interstitial pneumonia in most MCMV-infected mice.
- Multiple doses of cyclophosphamide increased lung virus titers but did not induce pneumonia.
Conclusions:
- MCMV-induced interstitial pneumonia in mice appears to be immunologically mediated.
- Direct viral damage is less likely to be the primary cause of MCMV lung pathology.
- The balance between viral replication and host immune response is critical in determining lung disease severity.