MDA7/IL-24 is an anti-viral factor that inhibits influenza virus replication

Melanoma differentiation associated gene-7 (mda-7)/interleukin- 24 (IL-24) is a secreted cytokine, which plays an essential role in tumor suppression. Although its role as a multifunctional protein affecting broad types of cancers is well described, functions of IL-24 in host defense against virus infection are yet to be determined. In this study, we explored the anti-viral effect of recombinant IL-24 treatment during influenza infection. Infection of human lung adenocarcinoma cells (A549) with the influenza A virus up-regulated IL-24 mRNA and protein expression in a time-dependent manner. Pre-treatment of A549 cells with recombinant IL-24 protein effectively suppressed viral plaque formation. Furthermore, IL-24 treatment of A549 cells reduced viral non-structural protein 1 (NS1) synthesis, whereas IL-24 knockdown resulted in increased viral replication. Interestingly, IL-24 treatment following influenza A virus infection led to up-regulation of interferon (IFN)-induced antiviral signaling. Taken together, our results suggest that IL-24 exerts a potent suppressive effect on influenza viral replication and can be used in the treatment of influenza infection.