Combined action of type I and type III IFN restricts initial replication of SARS-coronavirus in the lung but fails to inhibit systemic virus spread

Introduction STAT1-deficient mice are more susceptible to infection with SARS-Coronavirus (SARS-CoV) than type I IFN receptor-deficient mice. The increased susceptibility of STAT1-deficient mice is potentially due to the lack of functional type III IFN (IFN-λ) signalling. Methods We used mice lacking functional receptors for both type I and type III IFN (dKO) to evaluate the possibility that type III IFN plays a decisive role in SARS-CoV protection. Results We found that viral peak titres in lungs of dKO and STAT1-deficient mice were similar, although significantly higher than in wild-type mice. The kinetics of viral clearance from the lung was also comparable in dKO and STAT1-deficient mice. Surprisingly, however, infected dKO mice remained healthy, whereas infected STAT1-deficient mice developed liver pathology and eventually succumbed to neurological disease. Conclusion Our data suggest that the failure of STAT1-deficient mice to efficiently control initial SARS-CoV replication in the lung is due to impaired type I and type III IFN signaling, whereas the failure to control subsequent systemic viral spread is due to unrelated defects in STAT1-deficient mice.