Gamma Radiation Induces an Interferon-Independent Antiviral Activity in Human Macrophages

Gamma rays play a central role in biomedical applications, yet their implication on innate antiviral immunity remains insufficiently understood. Here we show that low-dose gamma irradiation (1.5–2 Gy) induces an antiviral state in human macrophage-like cells infected with influenza A virus (IAV). Irradiated macrophages exhibited increased transcription of type I interferon (IFN-I) genes and the antiviral effector MX1, despite the absence of detectable IFN-α or IFN-β proteins in culture supernatants. Notably, irradiated cells produced significantly fewer viral particles, as quantified by dynamic light scattering and confirmed by TCID ₅₀ assays. In parallel, gamma irradiation activated DNA damage response pathways, including transcriptional upregulation of TP53, H2AX, and NF-κB. These combined findings indicate that gamma rays can prime macrophages toward an IFN-independent antiviral state capable of restricting early IAV replication. This work expands the biomedical relevance of gamma radiation by demonstrating its capacity to modulate macrophage antiviral activity, offering insight into radiation–immune interactions with potential implications for radiotherapy, infectious disease control, and gamma-ray based technologies.