Related Experiment Videos
Influenza virus population dynamics in the respiratory tract of experimentally infected mice
Abstract:
Virus population dynamics in the lungs, trachea, and nasopharynx of Swiss-ICR mice were studied after respiratory challenge with mouse-adapted preparations of strain A2/Aichi/2/68 influenza virus. Markedly higher doses of virus were required to produce infection with nasopharyngeal challenge than with bronchoalveolar challenge. In all of the infections, the highest virus concentrations were observed in the lungs. Peak concentrations in the trachea were lower than in the lungs but higher than in the nasopharynx. Decreasing virus levels were observed by 120 h after challenge and were generally below detectable levels by the end of 10 days. A compartmental model of a single mathematical form was developed which provided close fits of the virus concentration measurements regardless of the challenge dose, site of initial deposition, or respiratory tissue considered. The model includes seven compartments with five associated rate parameters. The application of compartmental modeling techniques and expression of the virus population dynamics in mathematical terms is regarded as a new approach to the study of the pathogenesis of infections.
Insights
Influenza virus dynamics in mice show highest concentrations in lungs, with varying levels in the trachea and nasopharynx. A mathematical model accurately describes these virus population dynamics during infection.
Area of Science:
- Virology
- Mathematical Biology
- Respiratory Medicine
Background:
- Influenza virus infections pose a significant public health challenge.
- Understanding virus population dynamics is crucial for developing effective treatments.
- Previous studies have not fully elucidated the compartmental dynamics of influenza virus within the respiratory tract.
Purpose of the Study:
- To investigate the population dynamics of influenza virus in the lungs, trachea, and nasopharynx of mice.
- To develop and apply a mathematical compartmental model to describe virus dissemination and replication.
- To assess the impact of challenge dose and site of initial deposition on viral load.
Main Methods:
- Swiss-ICR mice were challenged with a mouse-adapted influenza A virus (A2/Aichi/2/68).
- Virus concentrations were quantified in lung, trachea, and nasopharynx tissues over time.
- A seven-compartment mathematical model was developed to fit the experimental data.
Main Results:
- Higher viral doses were needed for nasopharyngeal than bronchoalveolar challenge.
- The lungs consistently exhibited the highest virus concentrations.
- Tracheal and nasopharyngeal viral loads were lower than in the lungs, with trachea having higher concentrations than the nasopharynx.
- Viral levels decreased significantly by 120 hours post-challenge and were mostly undetectable by day 10.
- The compartmental model accurately described virus concentration data across different challenge conditions and tissues.
Conclusions:
- Influenza virus replication and dissemination vary significantly across different compartments of the mouse respiratory tract.
- Compartmental modeling provides a powerful mathematical framework for analyzing virus population dynamics.
- This approach offers new insights into the pathogenesis of respiratory viral infections.