Hyperoside inhibits PRRSV proliferation via the TLR4/NF-κB and p62-Nrf2-Keap1 signaling pathways, mediating inflammation and autophagy

》》文章原文链接：Hyperoside inhibits PRRSV proliferation via the TLR4/NF-κB and p62-Nrf2-Keap1 signaling pathways, mediating inflammation and autophagy

》》Journal：Microbiology Spectrum 

》》相关产品：3-Methyladenine (3-MA) (SJ-MN0032)

》》产品引用描述：

》》Abstract：

Porcine reproductive and respiratory syndrome virus (PRRSV) causes abortion and respiratory disease in swine, hindering the development of the pig farming industry worldwide. However, at present, there are no effective vaccines or drugs for PRRSV control. In this study, we evaluated the inhibitory effect of hyperoside on PRRSV replication in vitro and in vivo and explored the underlying mechanisms. Our results revealed that hyperoside significantly inhibited PRRSV infection in MARC-145 and porcine alveolar macrophages (PAMs). This inhibition was linked to the hyperoside-induced attenuation of pro-inflammatory cytokine (IL-1β, IL-6, IL-8, and TNF-α) upregulation induced by PRRSV infection, which was mediated by the suppression of the Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-kB) signaling pathway. Moreover, hyperoside alleviated the autophagy induced by PRRSV via p62/Nrf2/Keap1 signaling pathway activation. In vivo, hyperoside treatment led to an obvious decrease in PRRSV replication in piglets. Therefore, hyperoside may be a useful antiviral agent against PRRSV.IMPORTANCEPorcine reproductive and respiratory syndrome virus (PRRSV) causes abortion and respiratory disease in swine, which induces huge economic losses every year. However, there have been no effective vaccines or drugs for PRRSV control until now. Our present study found that the inhibitory effect of hyperoside on PRRSV replication in vitro and in vivo. Furthermore, we demonstrate that hyperoside inhibits PRRSV proliferation via inhibiting inflammation and autophagy through the Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) and p62-Nrf2-Keap1 signaling pathways. Hence, we believe that hyperoside may be a useful antiviral agent to control PRRSV.

》》部分实验数据展示：

Fig 6: Hyperoside inhibits PRRSV-induced autophagy. MARC-145 cells were pretreated with hyperoside (60 and 120 µM) or 3-MA (30 µM) for 2 h and then infected with PRRSV SD16 (MOI = 0.5) for 1 h, after which the medium was subsequently replaced with 3% FBS DMEM containing the indicated concentrations of hyperoside or 3-MA. After 24 h, the cells were harvested to analyze the expression of autophagy-related proteins (p62 and LC3I or LC3II) and the PRRSV N protein via western blotting (A). The quantitative analysis of the levels of the PRRSV N protein (B), p62 (C), LC3I (D), and LC3II (E), and the LC3II/LC3I ratio (F) was conducted via ImageJ.