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.

In 129 WT, IFNAR12/2 and IFNGR2/2 mice, clinical findings including weight loss data and morbidity were identical after infection with rMA15. 129 WT, IFNAR12/2 and IFNGR2/2 mice infected with rMA15 virus lost ,15% of their weight by day 4 and then steadily recovered over the next 5 days (Figure 1 ). In contrast, Urbani virus infected mice continued to gain weight through the course of infection ( Figure S1 ). In both cases, virus titers in the lungs peaked at day 2 post-infection, approaching titers of ,5.0610 7 pfu or TCID 50 /g (rMA15 or Urbani, respectively), and all were rapidly cleared by day 9 postinfection. Although virus titers were ,5-fold higher in IFNAR12/ 2 mice than titers in 129 WT mice on day 5 post-infection, we found that IFNAR12/2 and IFNGR2/2 mice showed no increase in susceptibility, pathogenesis or histological outcomes to rMA15 or Urbani virus infection. To examine the importance of cooperative IFN pathways in disease, IFN receptor double knockout (IFNAGR2/2) mice were infected with the Urbani virus; no increase in virus titer or weight loss was seen compared to