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.

We observed marked differences in pathology of lungs from 129 WT mice compared to STAT12/2 mice after infection with the rMA15 virus. To investigate whether STAT1 affected the inflammatory infiltrate, we isolated leukocytes from enzymatically disrupted mouse lungs harvested on day 8 post-infection and used cell surface markers to quantify macrophage (CD11c 2 /CD11b + / GR-1 int /MHCII + ), neutrophil (F480 2 /CD11b + /CD11c 2 /GR-1 + ), and eosinophil (CD11c 2 /Siglec + /GR-1 2 ) populations in 129 WT and STAT12/2 mice. A greater than 10-fold difference in leukocyte numbers was found between 129 WT and STAT12/ 2 infected mice ( Table 1 ). As shown in Table 1 , the eosinophil population increased from ,2% in 129 WT mice to ,30% in STAT12/2 mice and neutrophils increased from 3% in 129 WT mice to 35% in STAT12/2 mice. Additionally, the number of macrophages in STAT12/2 mice was more than double that detected in 129 WT mice. These numbers are concordant with the histological findings by H&E staining at 9 days post-infection.