作者
Chunyan Shao,Ziwei Yu,Tongwang Luo,Bin Zhou,Quanjiang Song,Zhuoyue Li,Xiaoqiang Yu,Sheng Jiang,Yingshan Zhou,Wanyu Dong,Xingdong Zhou,Xiaodu Wang,Houhui Song
摘要
Abstract Background Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly prevalent and endemic swine pathogen that can cause significant economic losses to the global swine industry. Host-targeted antiviral drugs have been developed as a new strategy for antiviral therapy. In this regard, selenium nanoparticles (SeNPs) have attracted increasing attention in the biomedical field, given their antiviral effects. The purpose of this study was to investigate whether chitosan-coated SeNPs (CS-SeNPs) could affect PRRSV replication in vitro. Methods In this study, CS-SeNPs were synthesized by chemical reduction and characterized by assessing the morphology, size distribution, zeta potential, and element composition. Marc-145 cells were infected with r-PRRSV-EGFP (0.1 MOI) and inoculated with CS-SeNPs (10 µM). Subsequently, the concentrations of hydrogen peroxide (H2O2) and glutathione (GSH), and glutathione peroxidase (GSH-Px) activity were measured using specific commercial assay kits. ORF5 RNA expression, viral titer, nucleocapsid (N) protein expression were assessed using qRT-PCR, TCID50, and Western blot. ROS generation, apoptosis rates, and JNK /caspase-3/PARP protein expression were evaluated using dihydroethidium staining, flow cytometry, and Western blot. Results The results showed that CS-SeNPs treatment significantly suppressed oxidative stress induced by r-PRRSV-EGFP infection by increasing GSH-Px activity, promoting GSH production, and inhibiting H2O2 synthesis. CS-SeNPs treatment significantly inhibited ORF5 gene expression, viral titers, and N protein of r-PRRSV-EGFP at 24 and 48 hours post-infection (hpi) in Marc-145 cells. The apoptosis rates initially increased by r-PRRSV-EGFP infection were significantly decreased by CS-SeNPs inoculation by inhibiting ROS generation, JNK phosphorylation levels, cleavage of caspase-3, and PARP mainly at 48 hpi. Conclusions Taken together, the present data demonstrated that CS-SeNPs synthesized by chemical reduction could enhance antioxidant capacity and effectively suppress PRRSV-induced apoptosis in Marc-145 cells via the ROS/JNK signaling pathway, thereby inhibiting PRRSV replication. This finding expands the treatment landscape for combating infections caused by PRRSV.