Characterization of the resistance of SJL/J mice to pneumonia virus of mice, a model for infantile bronchiolitis due to a respiratory syncytial virus

• Published in: PloS one 2012-10, Vol.7 (10), p.e44581-e44581
• Main Authors: Glineur, Stephanie, Tran Anh, Dao Bui, Sarlet, Michaël, Michaux, Charles, Desmecht, Daniel
• Format: Article
• Language: English
• Subjects: Adaptive immunity; Alleles; Alveoli; Animals; Biology; Bronchiolitis; Bronchiolitis - genetics; Bronchiolitis - immunology; Bronchiolitis - virology; Bronchopneumonia; Care and treatment; Children; Determinism; Disease; Disease control; Disease Models, Animal; Disease resistance; Dissection; Epithelial cells; Genetic Predisposition to Disease; Health aspects; Human health sciences; Humans; Immune system; Immunity; Immunologie & maladie infectieuse; Immunology & infectious disease; Immunosuppression; Inbreeding; Infant; Infants; Infections; Irradiation; Lung diseases; Lungs; Lymphocytes; Macrophages; Medicine; Mice; Morbidity; Murine pneumonia virus - immunology; Pneumonia; Polygenic inheritance; Proteins; resistance; Respiratory syncytial virus; Respiratory Syncytial Viruses - isolation & purification; Respiratory tract; Risk factors; Sciences de la santé humaine; segregation analysis; Strains (organisms); Studies; Veterinary Science; Virology; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0044581

Respiratory syncytial virus (RSV), a prominent cause of airway morbidity in children, maintains an excessive hospitalization rate despite decades of research. Host factors are assumed to influence the disease severity. As a first step toward identifying the underlying resistance mechanisms, we recently showed that inbred mouse strains differ dramatically as regards their susceptibility to pneumonia virus of mice (PVM), the murine counterpart of RSV. PVM infection in mice has been shown to faithfully mimic the severe RSV disease in human infants. This study aimed at dissecting the remarkable PVM-resistance shown by the SJL/J strain. To characterize its genetic component, we assessed clinical, physiopathological, and virological resistance/susceptibility traits in large first (F1) and second (F2) generations obtained by crossing the SJL/J (resistant) and 129/Sv (susceptible) strains. Then, to acquire conclusive in vivo evidence in support of the hypothesis that certain radiosensitive hematopoietic cells might play a significant role in PVM-resistance, we monitored the same resistance/susceptibility traits in mock- and γ-irradiated SJL/J mice. Segregation analysis showed that (i) PVM-resistance is polygenic, (ii) the resistance alleles are recessive, and (iii) all resistance-encoding alleles are concentrated in SJL/J. Furthermore, there was no alteration of SJL/J PVM-resistance after immunosuppression by γ-irradiation, which suggests that adaptive immunity is not involved. We conclude that host resistance to pneumoviruses should be amenable to genetic dissection in this mouse model and that radioresistant lung epithelial cells and/or alveolar macrophages may control the clinical severity of pneumovirus-associated lung disease.