Researchers reported that the host factor S100A4 directly supports influenza A virus replication through interactions with the viral M2 protein. In A549 alveolar epithelial cells, S100A4 knockdown or knockout attenuated viral replication, while overexpression enhanced it. The work also connected S100A4 to antiviral signaling: S100A4 overexpression reduced interferon-beta and suppressed interferon-stimulated genes such as ISG15 and BST2. The mechanistic link could inform host-targeted intervention strategies alongside antivirals.