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 innate immune response is a key first line of defense against invading pathogens and is dependent on various signaling pathways and sensors that ultimately induce hundreds of antiviral proteins to establish a suboptimal environment for replication and spread of invading pathogens [3, 4] . During virus infection the type I interferon (IFN) induction and signaling machinery is key to the initiation of this response. IFN induced from either infected cells or dendritic cells can activate an antiviral state in neighboring cells to signal that a viral infection is under way [5] . Not surprisingly, virus infections (mouse hepatitis virus, influenza virus, RSV, alphaviruses, flaviviruses, etc.) of rodents that lack type I or type II IFN regulatory networks result in increased pathogenesis and mortality, documenting the key role IFNs play in regulating disease outcomes [6] [7] [8] [9] [10] [11] [12] .