Sendai virus pneumonia in resistant (C57BL/6) and susceptible (DBA/2) mice

Abstract

The influence of interferon (IFN) on determining resistance in mice to Sendai virus pneumonia was studied in a resistant (C57BL/6) and susceptible (DBA/2) strain of mouse. A 100 fold difference in mortality was observed between the resistant and susceptible mice. A necrotizing bronchitis/bronchiolitis occurred in both DBA/2 and C57BL/6 mice. The DBA/2 mice also had a severe alveolitis and a much slower resolution of lesions than C57BL/6 mice. It was suggested that the resistance of the C57BL/6 mice was due to their ability to prevent alveolar infection. Although lung virus levels were similar in both strains, it was hypothesized that selective infection of alveoli with virus in DBA/2 mice may be responsible for the severe alveolitis observed only in DBA/2 mice. Adequate levels of lung IFN were produced in both strains, suggesting susceptibility was not related to the lack of IFN production. The C57BL/6 mice were more sensitive than DBA/2 mice to the protective effects of IFN, indicated by increased survival time of C57BL/6 mice after exogenous IFN administration. No apparent decrease in eventual mortality was observed however, which suggested that factors in addition to IFN were important in resistance. Following administration of anti-IFN serum, both mouse strains demonstrated a decreased mortality. It was hypothesized that anti-IFM serum, because it affected both strains equally, must have stimulated the immune response to the viral agent by some as yet unexplained mechanism. The increased sensitivity of C57BL/6 mice to IFN was also confirmed in in vitro virus inhibition studies using embryonic fibroblasts. C57BL/6 fibroblasts were protected against virus infection with lower concentrations of IFN than were DBA/2 fibroblasts; however, pulmonary macrophages of both mouse strains responded similarly to IFN. It was hypothesized that alveolar epithelium of C57BL/6 mice may also have increased sensitivity to IFN action which prevents alveolar infection in C57BL/6 mice. The resistance to Sendai virus in C57BL/6 mice was not reflected by any difference in natural killer (NK) cell activity in the two mouse strains or in a difference in NK cell sensitivity to IFN stimulations.