Abstract

Simple SummaryThe emergence of Duck Tembusu Virus (DTMUV), an avian pathogenic flavivirus, continues to be a major and persistent threat to the global waterfowl industry, resulting in substantial economic losses. Given that previous studies have shown Type I interferons offer insufficient protection, identifying novel and effective biotherapeutic strategies is critically important for veterinary disease control. A natural substance in the body called interferon-gamma is known to fight a wide range of viruses. However, its specific antiviral efficacy against Tembusu virus and the underlying mechanisms of action have not been reported in prior studies. This study aimed to investigate whether and how duck interferon-gamma can protect against this virus. We first found that the virus triggers duck cells to produce interferon-gamma. More importantly, experiments showed that this interferon-gamma has a strong dual protective effect: it can both prevent healthy duck cells from being infected and help already infected cells clear the virus. We discovered that it works by blocking the virus’s ability to make copies of itself inside cells. By analyzing all the genes turned on in cells treated with interferon-gamma, we identified that it activates the cell’s own defense systems, particularly those related to controlled cell death and early virus detection. In conclusion, this research clearly demonstrates that duck interferon-gamma is a powerful natural weapon against the duck Tembusu virus. These findings are valuable because they provide a solid scientific basis for developing new treatments, such as using interferon-gamma itself or the natural defense molecules it activates, to control this damaging poultry disease, which could help protect farmers’ livelihoods and ensure a stable supply of duck meat or eggs.Duck Tembusu virus (DTMUV), an emergingFlavivirus, is a major avian pathogen that imposes enormous economic losses on the global duck industry, necessitating urgent de