TYK2 and viral infectious disease: The mammalian innate immune system utilizes the type I interferon (IFN-I) family as the first line of defense against viruses, as well as other types of harmful microbes.1 In almost all cell types, IFN-I drives the transcription of IFN-stimulated genes (ISGs),2 whose products interfere with different stages of virus infection by many different mechanisms.3,4 All subtypes of IFN-I bind to and signal through the IFNAR heterodimeric receptor to activate the receptor-associated tyrosine kinases Janus kinase 1 (JAK1) and tyrosine kinase 2 (TYK2).