Title : New paradigms of IRF biology in virus infection
Abstract:
Interferon regulatory factors (IRFs) are classically viewed as transcription factors that induce interferons and antiviral genes during viral infection. Our work reveals that IRF biology extends beyond transcriptional control to include non-canonical functions that shape host responses. We identified a transcription-independent activity of IRF3 that promotes apoptotic elimination of infected cells (RIPA), providing an alternative antiviral effector mechanism. We further uncovered a distinct pathway in which IRF3 suppresses NF-κB–dependent inflammatory gene expression, thereby limiting excessive cytokine responses during respiratory viral infection (RIKA). Notably, IRF7 contains a homologous NF-κB–binding motif and similarly represses inflammatory gene expression, suggesting that this anti-inflammatory function represents a broader regulatory module within the IRF family. Together, these findings redefine IRFs as multifunctional regulators that coordinate antiviral defense while restraining pathological inflammation during viral infection.
