Primary infection of mice with high titer inoculum respiratory syncytial virus: characterization and response to antiviral therapy

Intranasal infection of BALB/c mice with respiratory syncytial virus (RSV)-A2 (0.5 × 108 – 2.0 × 108 plaque-forming units, PFU) produced disease characterized by weight loss (2–3 g) and mortality (60%–100%) with the mean day of death ranging from 6–7 d after infection. The extent of RSV disease was inoculum titer-dependent and required a replication competent virus. Lung titers of virus peaked at 0.5-1 × 106 PFU/g wet weight. Bronchoalveolar lavage fluid (BALF) levels of IL-1β, TNF-α, INF-γ IL-12, IL-6, MIP-1α, RANTES, and protein were elevated, whereas IL-2, IL-4, IL-5, IL-13, and IL-10 were unchanged. Histological assessment of lungs revealed marked inflammatory pathology characterized by bronchiolitis, vasculitis, and interstitial pneumonia. Whole-body plethysmography revealed significant disease-associated deficits of respiratory function. Therapy with ribavirin administered either by the intranasal, subcutaneous, or oral route significantly reduced disease in a dose-dependent manner. Delaying the ini...