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The cotton rat as an experimental model of human parainfluenza virus type 3 disease
Abstract:
Intranasal or aerosol inoculation of cotton rats (Sigmodon hispidus) with human parainfluenza virus type 3 (P3) produces pulmonary changes which closely resemble human disease due to this agent. Active viral replication resulted in peak titers by day 2 of infection. Viral antigen was localized by immunofluorescence in bronchial epithelial cells alone (aerosol inoculation) or epithelial and alveolar cells (intranasal instillation). Cytopathic effects in epithelial cells was noted as early as day 2, and marked cellular proliferation occurred by day 7. Intranasal instillation of virus resulted in development of patchy interstitial pneumonitis. Mononuclear cell infiltration in the peribronchial and perivascular areas peaked on days 6 and 7. A brisk systemic antibody response was measured both by complement fixation and virus neutralization techniques. These data establish the value of the cotton rat as an experimental model for the study of bronchiolitis and pneumonia due to P3. Since previous work has demonstrated that respiratory syncytial virus and Mycoplasma pneumoniae also will replicate and cause pulmonary disease in cotton rats, comparative studies in a single animal species are facilitated.
Insights
Cotton rats infected with human parainfluenza virus type 3 (P3) develop lung disease similar to humans. This model aids research into P3-induced bronchiolitis and pneumonia.
Area of Science:
- Virology
- Pathology
- Immunology
Background:
- Human parainfluenza virus type 3 (P3) causes respiratory illness in humans.
- Existing models may not fully replicate P3-induced pulmonary disease.
- Comparative studies of respiratory pathogens in animal models are beneficial.
Purpose of the Study:
- To establish and validate the cotton rat (Sigmodon hispidus) as an experimental model for human parainfluenza virus type 3 (P3) infection.
- To characterize the pulmonary pathology and immune response in cotton rats following P3 inoculation.
- To facilitate comparative studies of different respiratory viruses in a single animal model.
Main Methods:
- Cotton rats were inoculated intranasally or via aerosol with human parainfluenza virus type 3 (P3).
- Viral replication, antigen localization (immunofluorescence), and cytopathic effects were assessed.
- Pulmonary histopathology, including interstitial pneumonitis and inflammatory cell infiltration, was examined.
- Systemic antibody responses were measured using complement fixation and virus neutralization assays.
Main Results:
- Intranasal or aerosol P3 inoculation induced pulmonary changes mimicking human disease.
- Peak viral titers were observed by day 2 post-infection.
- Viral antigen was detected in bronchial and alveolar epithelial cells.
- Patchy interstitial pneumonitis and mononuclear cell infiltration were evident.
- A robust systemic antibody response was detected.
Conclusions:
- The cotton rat is a suitable model for studying P3-induced bronchiolitis and pneumonia.
- This model allows for detailed investigation of viral pathogenesis and host response.
- The utility of the cotton rat for comparative studies with other respiratory pathogens, such as respiratory syncytial virus and Mycoplasma pneumoniae, is supported.