Genetic lesions of type I interferon signalling in human antiviral immunity

Funding was provided by the Wellcome Trust [211153/Z/18/Z (C.J.A.D.), 207556/Z/17/Z (S.H.), 101788/Z/13/Z (R.E.R.)], Sir Jules Thorn Trust [12/JTA (S.H.)], and the British Medical Association (C.J.A.D).The concept that type I interferons (IFN-I) are essential to antiviral immunity derives from studies on animal models and cell lines. Virtually all pathogenic viruses have evolved countermeasures to IFN-I restriction, and genetic loss of viral IFN-I antagonists leads to virus attenuation. But just how important is IFN-I to antiviral defence in humans? The recent discovery of genetic defects of IFN-I signalling illuminates this and other questions of IFN biology, including the role of the mucosa-restricted type III IFNs (IFN-III), informing our understanding of the place of the IFN system within the concerted antiviral response. Here we review monogenic lesions of IFN-I signalling pathways and summarise the organising principles which emerge.Publisher PDFPeer reviewe