Evaluation of immunosuppression in a murine model of respiratory syncytial virus infection

Respiratory syncytial virus (RSV) is a major global pathogen, predominantly affecting infants, often leading to bronchiolitis and respiratory distress. Due to the replicative capacity of human RSV (hRSV) in the respiratory tract, limited in vivo models are available. BALB/c mice are semi-permissive to RSV infection, by utilising immunosuppression regimens more severe models of disease can be developed. This study aimed to establish a murine model of RSV infection, which induced clinical signs and inflammatory responses representative of hRSV infection. Female BALB/c mice received cyclophosphamide (CP) or saline, followed by intranasal vehicle or RSV at two titres. Clinical signs, body weight and temperature changes were monitored over 7 days. On Day 7, mice were sacrificed and bronchoalveolar lavage (BAL) cell counts and wet lung weights were recorded. CP-treated mice exhibited piloerection, mild gait, and hunched posture, accompanied by an increase in respiratory rate at the higher RSV titre. Additionally, CP-treated mice, inoculated with vehicle, showed significantly lower bodyweights on Days 0 to 1, and 3 to 5 compared to immunocompetent mice. Furthermore, CP-treated mice inoculated with RSV, had significantly higher lung weights compared to vehicle-inoculated mice. Increasing RSV titres induced significantly higher BAL total, neutrophil and lymphocyte counts. This study established a BALB/c mouse model that mimicked key aspects of hRSV and emphasized the importance of immunosuppression. Enhancing RSV permissiveness provides insights into infection severity, offering a robust platform for future therapeutic development.