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Small Animal Models for Human Metapneumovirus: Cotton Rat is More Permissive than Hamster and Mouse
Yu Zhang1, Stefan Niewiesk2, Jianrong Li3
1Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA. Zhang.707@osu.edu.
Abstract:
Human metapneumovirus (hMPV) is the second most prevalent causative agent of pediatric respiratory infections worldwide. Currently, there are no vaccines or antiviral drugs against this virus. One of the major hurdles in hMPV research is the difficulty to identify a robust small animal model to accurately evaluate the efficacy and safety of vaccines and therapeutics. In this study, we compared the replication and pathogenesis of hMPV in BALB/c mice, Syrian golden hamsters, and cotton rats. It was found that BALB/c mice are not permissive for hMPV infection despite the use of a high dose (6.5 log10 PFU) of virus for intranasal inoculation. In hamsters, hMPV replicated efficiently in nasal turbinates but demonstrated only limited replication in lungs. In cotton rats, hMPV replicated efficiently in both nasal turbinate and lung when intranasally administered with three different doses (4, 5, and 6 log10 PFU) of hMPV. Lungs of cotton rats infected by hMPV developed interstitial pneumonia with mononuclear cells infiltrates and increased lumen exudation. By immunohistochemistry, viral antigens were detected at the luminal surfaces of the bronchial epithelial cells in lungs. Vaccination of cotton rats with hMPV completely protected upper and lower respiratory tract from wildtype challenge. The immunization also elicited elevated serum neutralizing antibody. Collectively, these results demonstrated that cotton rat is a robust small animal model for hMPV infection.
Insights
Cotton rats are identified as a robust small animal model for studying human metapneumovirus (hMPV) infections. This model effectively replicates hMPV in the respiratory tract and shows promise for vaccine efficacy studies.
Area of Science:
- Virology
- Infectious Diseases
- Immunology
Background:
- Human metapneumovirus (hMPV) is a significant global cause of pediatric respiratory infections.
- The absence of vaccines and antivirals highlights the need for effective research models.
- Developing a suitable small animal model is crucial for hMPV therapeutic and vaccine development.
Purpose of the Study:
- To evaluate and compare the susceptibility and pathogenesis of hMPV in BALB/c mice, Syrian golden hamsters, and cotton rats.
- To identify a robust small animal model for hMPV research.
Main Methods:
- Intranasal inoculation of hMPV in BALB/c mice, Syrian golden hamsters, and cotton rats at varying doses.
- Assessment of viral replication in nasal turbinates and lungs.
- Histopathological examination of lung tissues.
- Immunohistochemical detection of viral antigens.
- Evaluation of vaccine efficacy and antibody response in cotton rats.
Main Results:
- BALB/c mice were not permissive to hMPV infection.
- Syrian hamsters showed efficient nasal turbinate replication but limited lung replication.
- Cotton rats exhibited efficient replication in both nasal turbinates and lungs.
- hMPV infection in cotton rats induced interstitial pneumonia with characteristic pathological features.
- Cotton rats vaccinated with hMPV demonstrated complete protection against wild-type challenge and developed neutralizing antibodies.
Conclusions:
- Cotton rats serve as a highly effective small animal model for hMPV infection.
- This model supports the study of hMPV pathogenesis and the evaluation of vaccine candidates.
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