# Duck IFNγ Restricts Duck Tembusu Virus Replication by Disrupting Viral RNA Synthesis/Translation

## TL;DR

Duck interferon-gamma protects against duck Tembusu virus by stopping viral replication and activating the duck's immune defenses.

## Contribution

This study reveals the dual antiviral mechanism of duck IFNγ against DTMUV, including RNA disruption and immune pathway activation.

## Key findings

- Duck IFNγ prevents DTMUV replication and clears existing virus in infected cells.
- Duck IFNγ disrupts viral RNA synthesis and translation.
- Duck IFNγ activates host defense pathways like programmed cell death and RIG-I-like receptor signaling.

## Abstract

The 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 emerging Flavivirus, is a major avian pathogen that imposes enormous economic losses on the global duck industry, necessitating urgent development of effective countermeasures. Although Interferon-gamma (IFNγ) is a crucial broad-spectrum antiviral cytokine, its role against DTMUV infection remains mechanistically undefined. In this study, we first demonstrated that DTMUV induced duck IFNγ (duIFNγ) production in immune and non-immune cells. Importantly, duIFNγ exhibited a dual anti-DTMUV function in vitro: it not only prevented viral replication but also displayed the capacity to clear existing virus from infected cells. Mechanistically, cycloheximide (CHX) experiments confirmed that duIFNγ exerts its antiviral effect by disrupting the viral RNA synthesis/translation phase. Furthermore, transcriptomic profiling (RNA-seq) precisely revealed that duIFNγ restricts DTMUV replication by activating multiple host defense pathways, notably Programmed Cell Death (e.g., Caspase signaling) and the RIG-I-like Receptor (RLR) signaling pathways. Collectively, these findings provide critical insights into the function and mechanism of duIFNγ in combating DTMUV in vitro, laying a robust theoretical foundation for exploring duIFNγ or its induced effectors as novel therapeutics for DTMUV infection.