Here, we report for the first time, that the cellular corepressor and negative immune regulator TRIM28 is the direct target of a signaling cascade involving the kinases PKR/p38/MSK1 during infection of human alveolar epithelial cells with HPAIV and contributes to the high expression levels of IFN-β, IL-6 and IL-8. The gene discussed is TRIM28; the disease is infection.