The antiviral activity of interferon-stimulated genes (ISGs) in influenza A virus infection

This review systematically delineates the antiviral activity of interferon-stimulated genes (ISGs) against influenza A virus (IAV) infection and their underlying mechanisms. IAV, a major respiratory pathogen, evades immune surveillance through antigenic drift and shift, leading to seasonal epidemics and pandemics. The host innate immune system recognizes IAV via pattern recognition receptors (PRRs), activating interferon (IFN) signaling pathways to induce ISG expression, thereby suppressing viral replication. ISGs target multiple stages of the IAV replication cycle through direct or indirect mechanisms. Additionally, IFN-induced non-coding RNAs reinforce antiviral defenses by modulating host genes or directly targeting viral genomes. Despite their critical roles, some viral proteins counteract ISGs, reflecting host-pathogen conflict. Further research is needed to fully elucidate ISG mechanisms, offering insights for novel antiviral strategies.