P136 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

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• 作者：T. Mahlakoiv ; D. Ritz ; L. Enjuanes ; M.A. M¨¹ller ; C. Drosten ; P. Staeheli
• 刊名：Cytokine
• 出版年：2012
• 出版时间：September, 2012
• 年：2012
• 卷：59
• 期：3
• 页码：562-563
• 全文大小：54 K

文摘

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-¦Ë) 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.