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 alpha and beta, 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.