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.

Cytokine induction following rMA15 virus infection was compared with Urbani virus infection ( Figure 4A-H) . Comparing cytokine transcript levels on days 2, 5 and 9 post-infection, we noted some similarities and important differences. Following rMA15 virus infection, 129 WT mice showed a 10-fold induction of TNFa transcripts by day 2 post-infection, followed by progressively reduced levels of expression that returned to baseline by day 9. While IFNAR12/2 mice showed similar kinetics as 129 WT mice, infection in IFNGR2/2 mice resulted in a continued rise in TNFa expression till day 9. In contrast, STAT12/2 mice had low baseline levels of TNFa expression through day 5, after which high levels of expression were noted at day 9, corresponding to the peak time of inflammation in the lungs, just prior to death.