SARS-CoV Pathogenesis Is Regulated by a STAT1 Dependent but a Type I, II and III Interferon Receptor Independent Mechanism

Frieman, Matthew B.; Chen, Jun; Morrison, Thomas E.; Whitmore, Alan; Funkhouser, William; Ward, Jerrold M.; Lamirande, Elaine W.; Roberts, Anjeanette; Heise, Mark; Subbarao, Kanta; Baric, Ralph S.

Histologic changes in the lungs of IFNAR12/2 and IFNGR2/2 mice were similar to 129 WT mice; the inflammation found in lung sections was temporally related to viral titer. At day 2 post-infection, a denuding bronchiolitis characterized by significant apoptosis and cell death in the airway epithelium was observed and conducting airways were obstructed by apoptotic debris. A mixed infiltrate composed of lymphocytes, neutrophils and eosinophils was seen surrounding the bronchial epithelium. By day 5 post-infection, significant inflammation was evident throughout the lungs and alveoli, resulting in a mild to moderate pneumonitis. As noted in lungs from 129 WT mice, the inflammation was clearing by day 9 post-infection; minimal inflammatory infiltrates remained in the periphery of the lungs and minor peribronchial lymphocytes remained.