A study shows that the human STING protein in lung epithelial cells acts as a barrier against the transmission of influenza A viruses (IAV) from birds to humans by limiting their replication.[1][4] STING activates the nuclear factor κB (NF-κB) pathway, which triggers genes that prevent the virus from spreading.[1][3] Influenza virus M1 protein binds to STING and blocks NF-κB activation, thereby facilitating virus replication in human cells.[1] Amino acid Gly90 in STING is crucial for NF-κB activation and restriction of IAV, as confirmed by experiments with mutated cells and mice.[1] The evolution of residue 115 in the M1 protein from Val to Ile allows the virus to bypass this barrier and gain an advantage in replication in human cells.[1][4] The M1-115 variant may serve as a molecular marker to predict the risk of IAV transmission between species.[1] Development of M1-STING disruptors could improve preparation for future influenza pandemics.[1]