NF-κB-dependent Induction of Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) and Fas/FasL Is Crucial for Efficient Influenza Virus Propagation

Activation of the transcription factor NF- Kappa B 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- Kappa B and its upstream regulator I Kappa B kinase are essential components of the innate antiviral immune response to infectious pathogens. In contrast to this common view we report here that NF- Kappa B activity promotes efficient influenza virus production. On a molecular level this is due to NF- Kappa B-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- Kappa B acts both proapoptotically and provirally in the context of an influenza virus infection.