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.

The Paramyxoviridae family includes some of the most important and ubiquitous disease-causing viruses of infants and children, most of which cause significant infections of the respiratory tract. Evidence is accumulating in humans that genetic factors are involved in the severity of clinical presentation. As a first step toward the identification of the genes involved, this study was undertaken to establish whether laboratory mouse strains differ in susceptibility to Sendai virus, the murine counterpart of human type-1 parainfluenza virus which, historically, has been used extensively in studies that have defined the basic biological properties of paramyxoviruses in general. With this purpose in mind, double-chamber plethysmography data were collected daily for 7 days after inoculation of Sendai virus 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 closely reflected the success of viral replication in the lungs and revealed a pattern of continuous variation with resistant, intermediate, and susceptible strains. The results unambiguously suggest that BALB/c (resistant) and 129Sv (susceptible) strains should be used in crossing experiments aimed at identifying the genes involved in resistance to Paramyxoviridae by the positional cloning approach.

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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.