Role of Interferon Regulatory Factor 1 in acute and chronic virus infections

Decades of research have defined the function of interferon regulatory factors (IRFs) in the antiviral immune response. Interferon regulatory factor-1 (IRF-1) is the founding member of the IRF family, with recognized antiviral effects across diverse virus infections. While most antiviral activities of IRF-1 were defined in vitro, fewer studies examined the role of IRF-1 during viral infection of an intact host. Taking advantage of mouse models of global or cell type-specific IRF-1 deficiency, recent studies demonstrate intriguing virus- and cell type-specific functions of IRF-1 during in vivo infection, underlining the complexity of this ancient transcription factor. Here, we review the role of IRF-1 during acute and chronic viral infections of an intact host, with particular focus on relating observations found in mouse models to those observed in a recent study of pediatric patients with IRF-1 insufficiency. By appreciating the complexity of IRF-1 in the immune response, we highlight several virus- and cell type-specific functions of IRF-1 in contributing to host antiviral immunity.