Differential resistance/susceptibility patterns to pneumovirus infection among inbred mouse strains
Dao Bui Tran Anh1, Pedro Faisca, Daniel J-M Desmecht
1Department of Pathology, University of Liège, Belgium.
Insights
This study found that different inbred mouse strains exhibit varying susceptibility to pneumonia virus of mice (PVM), a model for respiratory syncytial virus (RSV) in children. These findings are crucial for identifying host genes that influence PVM and RSV disease severity.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Respiratory syncytial virus (RSV) causes significant airway illness in infants.
- Host genetic factors are hypothesized to influence RSV disease severity and hospitalization rates.
Purpose of the Study:
- To determine if inbred mouse strains differ in susceptibility to pneumonia virus of mice (PVM), a murine model for RSV.
- To lay the groundwork for identifying genes controlling pneumovirus infection severity.
Main Methods:
- Six inbred mouse strains were inoculated with PVM.
- Pulmonary function was assessed daily using plethysmography and carbon monoxide uptake.
- Lung viral loads and histology were evaluated post-infection.
Main Results:
- Significant variation in PVM susceptibility was observed across mouse strains, with identified resistant, intermediate, and susceptible groups.
- Pulmonary function correlated with viral replication levels in the lungs.
- Specific strains (SJL, 129/Sv, BALB/c, C57BL/6, DBA/2) were identified as suitable for genetic studies.
Conclusions:
- Inbred mouse strains provide a valuable model for studying host genetic control of pneumovirus infections.
- Identified susceptible and resistant strains are recommended for genetic mapping studies to find genes influencing viral replication and pulmonary inflammation.
Abstract:
Respiratory syncytial virus (RSV) is a prominent cause of airway morbidity in children under 1 yr of age. It is assumed that host factors influence the severity of the disease presentation and thus the need for hospitalization. As a first step toward the identification of the underlying genes involved, this study was undertaken to establish whether inbred mouse strains differ in susceptibility to pneumonia virus of mice (PVM), the murine counterpart of RSV, which has been shown to accurately mimic the RSV disease of children. With this purpose in mind, double-chamber plethysmography and carbon monoxide uptake data were collected daily for 7 days after inoculation of PVM in six inbred strains of mice. In parallel, histological examinations and lung viral titration were carried out from day 5 to day 7 after inoculation. Pulmonary structure/function values reflected the success of viral replication in the lungs and revealed a pattern of continuous variation, with resistant, intermediate, and susceptible strains. The results suggest that SJL (resistant) and 129/Sv (susceptible) strains should be used in crossing experiments aimed at identifying genes controlling pneumovirus replication by the positional cloning approach. Similarly, crossing experiments using BALB/c or C57BL/6 (resistant) and DBA/2 or 129/Sv (susceptible) will allow the identification of the genes involved in the control of pulmonary inflammation during pneumovirus infection.
