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.

This hypothesis was tested by inoculating control BALB/c mice and IL28Ra2/2 mice with the Urbani virus, rMA15 virus or PBS. There was no weight loss in either BALB/c or IL28Ra2/2 mice infected with the Urbani virus (data not shown), thus the lack of IFNl signaling did not potentiate clinical disease. Lungs from Urbani virus infected BALB/c and IL28Ra2/2 mice were harvested at 2, 4, 7 and 21 days post-infection. We found no difference between the titers of virus in the lungs of BALB/c and IL28Ra2/2 mice ( Figure 5B ). Lungs from infected mice were analyzed by H&E staining. Urbani virus infection of IL28Ra2/2 mice produced mild inflammation that peaked at day 2 and resolved by day 7 post-infection; replicating the pattern seen in BALB/c mice ( Figure S4A ). rMA15 virus infection caused .20% weight loss and/or death by day 4-5 post-infection in BALB/c and similar findings in IL28Ra2/2 mice (data not shown); both lost ,20% weight by day 4 post-infection. Lungs were harvested at days 2 and 4 postinfection and no differences in virus titers were observed ( Figure 5B ). Both mouse strains showed peak virus titers at day 2 with a 2-3 log decrease by day 4. Lung pathology was analyzed by H&E staining. Both BALB/c and IL28Ra2/2 mice showed similar high levels of inflammation at 2 and 4 days post-infection, but remarkably similar pathologic outcomes ( Figure S4B ). Taken together, we found no role for IFNl in protection from infection with either the Urbani or rMA15 strains of SARS-CoV.