Porcine reproductive and respiratory syndrome virus (PRRSV) is a prevalent and endemic swine pathogen that causes significant economic losses in the global swine industry. Commercial vaccines provide limited protection against this virus, and no highly effective therapeutic drugs are yet available. In this study, we first screened a library of 386 natural products and found that xanthohumol (Xn), a prenylated flavonoid found in hops, displayed high anti-PRRSV activity by inhibiting PRRSV adsorption onto and internalization into cells. Transcriptome sequencing revealed that Xn treatment stimulates genes associated with the antioxidant response in the nuclear factor-erythroid 2-related factor 2 (Nrf2) signalling pathway. Xn causes increased expression of Nrf2, HMOX1, GCLC, GCLM, and NQO1 in Marc-145 cells. The action of Xn against PRRSV proliferation depends on Nrf2 in Marc-145 cells and porcine alveolar macrophages (PAMs). This finding suggests that Xn significantly inhibits PRRSV proliferation and decreases viral-induced oxidative stress by activating the Nrf2-HMOX1 pathway. This information should be helpful for developing a novel prophylactic and therapeutic strategy against PRRSV infection.

中文翻译：

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Xanthohumol抑制PRRSV增殖并通过Nrf2-HMOX1轴减轻PRRSV诱导的氧化应激。

猪繁殖与呼吸综合症病毒（PRRSV）是一种流行的地方性猪病原体，在全球养猪业中造成重大的经济损失。商业疫苗对这种病毒的保护作用有限，并且尚无高效的治疗药物。在这项研究中，我们首先筛选了386种天然产物的库，并发现啤酒花中发现的异黄酮类黄酮黄腐酚（Xn）通过抑制PRRSV吸附到细胞中和内在化来显示高抗PRRSV活性。转录组测序显示，Xn处理可刺激与核因子-类胡萝卜素2相关因子2（Nrf2）信号传导途径中的抗氧化反应相关的基因。Xn导致Marc-145细胞中Nrf2，HMOX1，GCLC，GCLM和NQO1的表达增加。Xn对PRRSV增殖的作用取决于Marc-145细胞和猪肺泡巨噬细胞（PAM）中的Nrf2。这一发现表明，Xn通过激活Nrf2-HMOX1途径，显着抑制PRRSV增殖并降低病毒诱导的氧化应激。该信息应有助于开发针对PRRSV感染的新型预防和治疗策略。