Diaz Fabian E, McGill Jodi L
Department of Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, IA, United States.
Immunohorizons. 2025 Aug 25;9(9). doi: 10.1093/immhor/vlaf036.
Human and bovine respiratory syncytial virus (RSV) are significant causes of morbidity and mortality in human and cattle populations worldwide, respectively. RSV disease is characterized by deleterious inflammatory immune responses as well as generation of radical oxygen species in the airways. Recent reports have shown antiviral and anti-inflammatory activity of NRF2 agonists and immunometabolite derivatives 4-octyl-itaconate (4-OI) and dimethyl fumarate (DMF), suggesting their potential to protect against viral-induced inflammation. Here, we evaluated whether 4-OI or DMF impact human and bovine RSV replication and its associated inflammatory response in vitro and the efficacy of these NRF2 agonists in preventing RSV disease in a murine model. We observed that 4-OI and DMF inhibited the early inflammatory response to RSV as well as reduced infectious titers in epithelial cells. Moreover, mice treated with 4-OI or DMF were partially protected against RSV-induced weight loss and airway inflammation and showed reduced viral loads and interleukin-6 levels in the lung. Overall, these results support the use of NRF2 agonists 4-OI and DMF in the prevention of RSV disease in target populations.
人类呼吸道合胞病毒（RSV）和牛呼吸道合胞病毒分别是全球人类和牛群发病和死亡的重要原因。RSV疾病的特征是有害的炎症免疫反应以及气道中活性氧的产生。最近的报告显示了NRF2激动剂以及免疫代谢物衍生物4-辛基衣康酸（4-OI）和富马酸二甲酯（DMF）的抗病毒和抗炎活性，表明它们具有预防病毒诱导炎症的潜力。在此，我们评估了4-OI或DMF是否会影响人源和牛源RSV在体外的复制及其相关炎症反应，以及这些NRF2激动剂在小鼠模型中预防RSV疾病的疗效。我们观察到，4-OI和DMF抑制了对RSV的早期炎症反应，并降低了上皮细胞中的感染滴度。此外，用4-OI或DMF处理的小鼠对RSV诱导的体重减轻和气道炎症有部分保护作用，并且肺部的病毒载量和白细胞介素-6水平降低。总体而言，这些结果支持使用NRF2激动剂4-OI和DMF预防目标人群中的RSV疾病。
