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.

The similarities between STAT12/2 mice infected with SARS-CoV and elderly individuals infected with SARS-CoV during the epidemic are intriguing. Recent work has shown that in cells from aged hosts, STAT1 signaling cascades are less responsive to stimuli; STAT1 signaling in aged macrophages were hypo-responsive to IFNc [49] . As observed in our study, IFNc expression increases substantially in STAT12/2 mice. We hypothesize that this may be in response to a lack of negative feedback via the STAT1 signaling pathway. During the SARS epidemic, aged individuals were the cohort with most severe disease and highest mortality rates [53] . We propose that altered STAT1 signaling in aged individuals may have lead to increased susceptibility to severe disease.