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.

Infection with the epidemic (Urbani) and mouse adapted strains of SARS-CoV caused increased pathology in the STAT12/2 mice. Thus, it seems likely that the mouse adapted mutations in rMA15 enhanced the intrinsic pathogenic properties of SARS-CoV to produce severe end stage lung disease in the mice. However, SARS-CoV Urbani spreads from the respiratory tract into the spleen and liver of STAT12/2 mice. This suggests that although the damage may have been induced by viral infection, the pathology results from the host's response to the infection, though it is not clear whether this represents a normal pattern of spread or whether mutations have evolved in the virus that promote spread and distribution to other organs. Similar findings were seen in autopsy samples from individuals who died from SARS. Airways were intact and regenerated while acute cases showed spread to the outer pulmonary parenchyma [52] .