NF-κB-dependent induction of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas/FasL is crucial for efficient influenza virus propagation

Abstract

Activation of the transcription factor NF-κB is a hallmark of infections by viral pathogens including influenza viruses. Because gene expression of many proinflammatory and antiviral cytokines is controlled by this factor, the concept emerged that NF-κB and its upstream regulator IκB kinase are essential components of the innate antiviral immune response to infectious pathogens. In contrast to this common view we report here that NF-κB activity promotes efficient influenza virus production. On a molecular level this is due to NF-κB-dependent viral induction of the proapoptotic factors tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and FasL, which enhance virus propagation in an autocrine and paracrine fashion. Thus, NF-κB acts both proapoptotically and provirally in the context of an influenza virus infection.