IFN regulatory factor 3 in health and disease

Immunity to viruses requires an array of critical cellular proteins that include IFN regulatory factor 3 (IRF3). Consequently, most viruses that infect vertebrates encode proteins that interfere with IRF3 activation. This review describes the cellular pathways linked to IRF3 activation and where those pathways are targeted by human viral pathogens. Moreover, key regulatory pathways that control IRF3 are discussed. Besides viral infections, IRF3 is also involved in resistance to some bacterial infections, in anticancer immunity, and in anticancer therapies involving DNA damage agents. A recent finding shows that IRF3 is needed for T cell effector functions that are involved in anticancer immunity and also in T cell autoimmune diseases. In contrast, unregulated IRF3 activity is clearly not beneficial, considering it is implicated in certain interferonopathies, in which heightened IRF3 activity leads to IFN-b–induced disease. Therefore, IRF3 is involved largely in maintaining health but sometimes contributing to disease. The Journal of Immunology, 2020, 205: 1981–1989.