How cells respond to interferons revisited: From early history to current complexity

A brief account of how I became involved in interferon research is followed by recollections of key experiments that led to the discovery of the roles of the JAKs and STATs in interferon-dependent signaling. I then outline the complex responses of cells to interferons, including the roles of kinases other than JAKs and transcription factors other than STATs, differential responses to interferons α and β, modulation of response by prior exposure to other cytokines (“priming”), cytokine-dependent induction of high level expression of STATs 1 and 3 and the activation of a new set of genes by these unphosphorylated STATs, and diverse patterns of STAT activation in different cell types in response to a single interferon.