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.

IFNLR antibody in IFNAR12/2 mice BALB/c and 129 WT mice respond differently to rMA15 virus infection; rMA15 is lethal in BALB/c mice but only causes transient weight loss in 129/Sv mice. To analyze the effects of knocking out both Types I and III IFN signaling pathways, we treated IFNAR12/2 mice (on the 129 background) with neutralizing antibodies to IL28Ra, the receptor used by IFNl. Mice were injected with 100 mg of anti-IL28Ra antibody at days -1, 1, 3, 5 and 7 days post-infection as described in the literature [37] . We found no difference in weight loss or pathogenesis of rMA15 in these mice compared to mice injected with PBS ( Figure 6 ). Mice showed 15% weight loss by day 4 postinfection but recovered by day 9, ending at their starting weight. Lungs were analyzed at days 2, 4 and 9 post-infection and showed no difference in pathology compared to IFNAR12/2 mice (data not shown). Both groups of mice showed epithelial cell denudation at 2 day post-infection and repair and clearance by day 9. Virus titers were only slightly increased over PBS injected mice but the difference was not statistically significant. This suggests that the inhibition of both Type I and Type III signaling in mice does not increase the pathogenesis of the rMA15 virus and neither protect 129 mice from disease.