The Pathophysiology of Enhanced Susceptibility to Murine Cytomegalovirus Respiratory Infection during Short-term Exposure to 5 ppm Nitrogen Dioxide

To determine whether exposure to nitrogen dioxide (NO2) affects respiratory tract susceptibility to viral infection, CD-1 mice were inoculated intratracheally with murine cytomegalovirus (MCMV) during exposure to varying concentrations of NO2. Exposure lasted for 6 h per day; it began 2 consecutive days prior to instillation of MCMV and continued for 4 days after virus inoculation. Exposure to 5 ppm NO2 resulted in MCMV proliferation and a mild bronchopneumonia in some animals inoculated with 10(2) plaque-forming units of virus. Importantly, this inoculum was too low to produce either viral replication or histologic abnormalities in the lungs of air-exposed animals. We also found that the amount of virus required to infect animals exposed to 5 ppm of NO2 was 100-fold lower than that needed to consistently produce infection in air-exposed animals. Animals exposed to 5 ppm NO2 also exhibited depressed phagocytosis of colloidal Au198 in vivo as well as diminished macrophage destruction of instilled MCMV compared to air-exposed animals. These results demonstrate that exposure to 5 ppm NO2, although not associated with evidence of overt lung injury per se, is nevertheless capable of predisposing the lower respiratory tract to viral infection.