Related Experiment Videos
Development of a murine hypothermia model for study of respiratory tract influenza virus infection
J P Wong1, E G Saravolac, J G Clement
1Medical Countermeasures Section, Defence Research Establishment Suffield, Alberta, Canada.
Abstract:
A hypothermia model was developed to predict mortality and morbidity caused by respiratory influenza virus infection in mice. To increase virulence, egg-propagated influenza A/PR/8 virus was adapted for growth in mice by four blind serial passages. The mouse-adapted influenza A virus was then used to infect groups of BALB/c mice via the intranasal route, and the 50% lethal dose (LD50) was determined. Rectal temperature of the infected mice was monitored daily, and survival rate was determined at day 14 after infection. The lowest average body temperature recorded in infected mice was approximately 10 degrees C below that in noninfected mice. In mice that developed hypothermia, with body temperature of 32 degrees C or lower, morbidity and mortality inevitably occurred. In this study, the LD50 and the 50% hypothermia-inducing dose (HID50) for mouse-adapted influenza A virus were compared and calculated to be at the same dose. These results suggest that the HID50 model could be used to predict mortality and morbidity associated with influenza virus infection in mice. This model could potentially be used to substantially reduce the time and extent of suffering inflicted on experimental animals due to viral infections, and therefore may serve as a more humane alternative to LD50 determinations.
Insights
A novel hypothermia model can predict influenza virus infection outcomes in mice. The 50% hypothermia-inducing dose (HID50) correlates with mortality, offering a more humane alternative to traditional lethal dose studies.
Area of Science:
- Virology
- Immunology
- Animal Models
Background:
- Influenza virus infections pose significant public health risks.
- Accurate prediction of disease severity in animal models is crucial for research.
- Existing methods like the 50% lethal dose (LD50) can be resource-intensive and raise ethical concerns.
Purpose of the Study:
- To develop and validate a hypothermia model for predicting influenza virus-induced mortality and morbidity in mice.
- To compare the efficacy of the hypothermia-inducing dose (HID50) with the traditional LD50.
- To explore a potentially more humane alternative for influenza research in animal models.
Main Methods:
- Adaptation of influenza A/PR/8 virus for enhanced virulence in mice through serial passages.
- Intranasal inoculation of BALB/c mice with the adapted virus.
- Daily monitoring of rectal temperature and determination of survival rates at day 14 post-infection.
- Calculation of the 50% lethal dose (LD50) and the 50% hypothermia-inducing dose (HID50).
Main Results:
- Mouse-adapted influenza A virus successfully induced hypothermia (body temperature ~10°C below controls).
- Mice developing hypothermia (≤32°C) invariably experienced morbidity and mortality.
- The 50% hypothermia-inducing dose (HID50) was found to be equivalent to the 50% lethal dose (LD50).
Conclusions:
- The hypothermia model effectively predicts mortality and morbidity in mouse models of influenza virus infection.
- The HID50 serves as a reliable indicator of influenza virus pathogenicity.
- This model offers a promising, more humane alternative to LD50 determinations, potentially reducing animal suffering.