Pathogenesis of human metapneumovirus lung infection in BALB/c mice and cotton rats
Marie-Eve Hamelin1, Kevin Yim, Katie H Kuhn
1Research Center in Infectious Diseases of the Centre Hospitalier Universitaire de Québec, and Laval University, Québec City, Canada.
Abstract:
Human metapneumovirus (hMPV) is a newly described member of the Paramyxoviridae family causing acute respiratory tract infections, especially in young children. We studied the pathogenesis of this viral infection in two experimental small animal models (BALB/c mice and cotton rats). Significant viral replication in the lungs of both animals was found following an intranasal challenge of 10(8) 50% tissue culture infectious doses (TCID50) and persisted for <2 and <3 weeks in the case of cotton rats and mice, respectively. Peak viral loads were found on day 5 postinfection in both mice (mean of 1.92 x 10(7) TCID50/g lung) and cotton rats (mean of 1.03 x 10(5) TCID50/g). Clinical symptoms consisting of breathing difficulties, ruffled fur, and weight loss were noted in mice only around the time of peak viral replication. Most significant pulmonary inflammatory changes and peak expression of macrophage inflammatory protein 1alpha, gamma interferon, and RANTES occurred at the time of maximal viral replication (day 5) in both models. Cellular infiltration occurred predominantly around and within alveoli and persisted for at least 21 days in mice, whereas it was more limited in time with more peribronchiolitis in cotton rats. Both animal models would be of great value in evaluating different therapeutic agents, as well as vaccine candidates against hMPV.
Insights
Human metapneumovirus (hMPV) causes respiratory infections in children. This study shows hMPV replicates in mouse and cotton rat lungs, with inflammation and symptoms appearing in mice, validating these models for therapeutic research.
Area of Science:
- Virology
- Immunology
- Pathogenesis
Background:
- Human metapneumovirus (hMPV) is a significant respiratory pathogen, particularly in young children.
- hMPV belongs to the Paramyxoviridae family and causes acute respiratory tract infections.
Purpose of the Study:
- To investigate the pathogenesis of hMPV infection in experimental animal models.
- To evaluate BALB/c mice and cotton rats as models for hMPV pathogenesis and therapeutic evaluation.
Main Methods:
- Intranasal challenge of BALB/c mice and cotton rats with hMPV (10^8 TCID50).
- Monitoring of viral replication, clinical signs, pulmonary inflammation, and immune mediator expression.
- Histopathological analysis of lung tissues.
Main Results:
- Significant hMPV replication occurred in the lungs of both mice and cotton rats, persisting for up to 3 weeks.
- Peak viral loads were observed on day 5 post-infection in both models.
- Mice exhibited clinical symptoms (respiratory distress, weight loss) and sustained pulmonary inflammation, while cotton rats showed more transient inflammation and peribronchiolitis.
Conclusions:
- BALB/c mice and cotton rats effectively model hMPV pathogenesis, demonstrating viral replication and host immune responses.
- These animal models are valuable for assessing the efficacy of antiviral therapies and vaccine candidates against hMPV.
