Rotaviruses (RV) are a major cause of severe gastroenteritis, particularly in neonatal piglets. Despite the availability of effective vaccines, the development of antiviral therapies for RV remains an ongoing challenge. Retinoic acid (RA), a metabolite of vitamin A, has been shown to have anti-oxidative and antiviral properties. However, the mechanism by which RA exerts its intestinal-protective and antiviral effects on RV infection is not fully understood. The study investigates the effects of RA supplementation in Duroc × Landrace × Yorkshire (DLY) piglets challenged with RV. Thirty-six DLY piglets were assigned into six treatments, including a control group, RA treatment group with two concentration gradients (5 and 15 mg/d), RV treatment group, and RV treatment group with the addition of different concentration gradients of RA (5 and 15 mg/d). Our study revealed that RV infection led to extensive intestinal architecture damage, which was mitigated by RA treatment at lower concentrations by increasing the villus height and villus height/crypt depth ratio ( < 0.05), enhancing intestinal stem cell signaling and promoting intestinal barrier functions. In addition, 15 mg/d RA supplementation significantly increased NRF2 and HO-1 protein expression ( < 0.05) and GSH content ( < 0.05), indicating that RA supplementation can enhance anti-oxidative signaling and redox homeostasis after RV challenge. Additionally, the research demonstrated that RA exerts a dual impact on the regulation of autophagy, both stimulating the initiation of autophagy and hindering the flow of autophagic flux. Through the modulation of autophagic flux, RA influence the progression of RV infection. These findings provide new insights into the regulation of redox hemostasis and autophagy by RA and its potential therapeutic application in RV infection.

中文翻译：

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视黄酸通过调节仔猪氧化还原稳态和自噬通量减轻轮状病毒引起的肠道损伤

轮状病毒 (RV) 是严重胃肠炎的主要原因，尤其是新生仔猪。尽管已经有了有效的疫苗，但开发 RV 抗病毒疗法仍然是一个持续的挑战。视黄酸 (RA) 是维生素 A 的代谢产物，已被证明具有抗氧化和抗病毒特性。然而，RA 对 RV 感染发挥肠道保护和抗病毒作用的机制尚不完全清楚。该研究调查了补充 RA 对接受 RV 攻击的杜洛克×长白×约克夏 (DLY) 仔猪的影响。将 36 头 DLY 仔猪分为 6 个处理，包括对照组、两个浓度梯度（5 和 15 mg/d）的 RA 治疗组、RV 治疗组和添加不同浓度梯度 RA 的 RV 治疗组（ 5 和 15 毫克/天）。我们的研究表明，RV 感染导致广泛的肠道结构损伤，而较低浓度的 RA 治疗可通过增加绒毛高度和绒毛高度/隐窝深度比（< 0.05）、增强肠道干细胞信号传导并促进肠道屏障功能来减轻这种损伤。此外，补充 15 mg/d RA 显着增加 NRF2 和 HO-1 蛋白表达（< 0.05）以及 GSH 含量（< 0.05），表明补充 RA 可以增强 RV 攻击后的抗氧化信号传导和氧化还原稳态。此外，研究表明，RA 对自噬的调节具有双重影响，既刺激自噬的启动，又阻碍自噬流的流动。通过调节自噬流，RA 影响 RV 感染的进展。这些发现为 RA 对氧化还原止血和自噬的调节及其在 RV 感染中的潜在治疗应用提供了新的见解。