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.

Lungs from the various mouse strains infected with SARS-CoV were analyzed for severity of histopathology ( Figure 2 ). In the 129 WT mice, rMA15 virus caused a denuding bronchiolitis at 2 days post-infection with significant apoptosis of airway epithelial cells (noted by multilobed nuclei, condensed chromatin and nuclear blebbing), accumulation of apoptotic debris within the airways and perivascular cuffing caused predominately by lymphocytes. Similar lesions have been noted in BALB/c and C57BL6 mice [26] . rMA15 virus infection was primarily localized in airway epithelium at day 2 post-infection ( Figure 3 ) and did not disseminate to other areas of the lung or respiratory tract. Some perivascular cuffing was noted in the vasculature by day 2 postinfection as well. By day 5, the denuding bronchiolitis, obstruction of the conducting airways by apoptotic debris and apoptosis of the airway epithelium were rarely observed, although perivascular cuffing and a mixed inflammatory response with lymphocytic infiltration of eosinophils, neutrophils and macrophages was more prominent. By day 9 post-infection, the remaining inflammation caused by rMA15 virus infection was primarily found in peribronchiolar areas ( Figure 2 ).