Relative timing of type I interferon response and virus replication determines disease outcome during respiratory virus infection

Abstract

Abstract Type 1 interferons (IFN-I) generally protect mammalian hosts from virus infections, but in some cases, IFN-I is pathogenic. Because IFN-I is protective, it is commonly used to treat virus infections for which no specific approved drug or vaccine is available. The Middle East respiratory syndrome-coronavirus (MERS-CoV) is such an infection, yet little is known about the role of IFN-I in this setting. Here we show that IFN-I signaling is protective during MERS-CoV infection. Blocking IFN-I results in delays in virus clearance and impaired MERS-CoV-specific T cell responses. Administration of IFN-I within 1 day post infection (dpi) protected mice from lethal infection. In marked contrast, delayed IFN-I enhanced the inflammatory response, converting a sublethal to a fatal infection. Together, these results suggest the relative timing of IFN-I signaling and maximal virus replication is key in determining the disease outcome and that IFNab should be used cautiously to treat virus infections.