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.

Several studies have demonstrated the importance of the innate response in viral clearance. Respiratory syncytial virus (RSV) and SARS-CoV require MyD88 to produce an effective immune response to control severe infection in the lung [25, 26] . The Mx gene product plays an important role in the susceptibility of rodents to influenza virus infection and could regulate severity of SARS-CoV disease in vivo as well [27] . Glass et al demonstrated that SARS-CoV was cleared from the lungs of wildtype C57BL/6 mice and strains that lacked that T, B and NK cells with similar kinetics, suggesting that the innate immune response alone is sufficient for viral clearance [28] . Hogan et. al . also demonstrated that STAT1, a key modulator of IFN a/b, l, c signaling, was required for the resolution of wildtype SARS-CoV infection, once again indicating the importance of the innate response in the clearance of SARS-CoV [29] .