Combined action of type I and type III interferon restricts initial replication of severe acute respiratory syndrome coronavirus in the lung but fails to inhibit systemic virus spread

• Published in: Journal of general virology Vol. 93; no. Pt 12; pp. 2601 - 2605
• Main Authors: MAHLAKOIV, Tanel, RITZ, Daniel, MORDSTEIN, Markus, DEDIEGO, Marta L, ENJUANES, Luis, MÜLLER, Marcel A, DROSTEN, Christian, STAEHELI, Peter
• Format: Journal Article
• Language: English
• Published: Reading Society for General Microbiology 01.12.2012
• Subjects: Animals; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Interferon Type I - immunology; Interferons - immunology; Lung - immunology; Lung - virology; Mice; Mice, Inbred C57BL; Mice, Knockout; Microbiology; Miscellaneous; Receptor, Interferon alpha-beta - deficiency; Receptor, Interferon alpha-beta - genetics; Receptor, Interferon alpha-beta - immunology; Receptors, Interferon - deficiency; Receptors, Interferon - genetics; Receptors, Interferon - immunology; SARS coronavirus; SARS Virus - immunology; SARS Virus - pathogenicity; SARS Virus - physiology; STAT1 Transcription Factor - deficiency; STAT1 Transcription Factor - genetics; STAT1 Transcription Factor - immunology; Virology; Virus Replication - immunology; Infection; Virus; Lung disease; Coronavirus; Respiratory disease; Viral disease; Lung; Severe acute respiratory syndrome; Replication; Interferon; Coronaviridae; Nidovirales
• ISSN: 0022-1317; 1465-2099; 1465-2099
• DOI: 10.1099/vir.0.046284-0

STAT1-deficient mice are more susceptible to infection with severe acute respiratory syndrome coronavirus (SARS-CoV) than type I interferon (IFN) receptor-deficient mice. We used mice lacking functional receptors for both type I and type III IFN (double knockout, dKO) to evaluate the possibility that type III IFN plays a decisive role in SARS-CoV protection. We found that viral peak titres in lungs of dKO and STAT1-deficient mice were similar, but significantly higher than in wild-type mice. The kinetics of viral clearance from the lung were 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. Our data suggest that the failure of STAT1-deficient mice to control initial SARS-CoV replication efficiently in the lung is due to impaired type I and type III IFN signalling, whereas the failure to control subsequent systemic viral spread is due to unrelated defects in STAT1-deficient mice.