Wang Bin, Che Lihe, Zhang Peng, Sun Luyao, Yu Yue, Du Na
Department of Infectious Diseases, The First Hospital of Jilin University, No.1 Xinmin Street, 130021, Changchun, China.
Arch Virol. 2025 Sep 16;170(10):207. doi: 10.1007/s00705-025-06392-5.
Resveratrol-loaded nanoparticles (RES-NPs) have been found to reduce enterovirus 71 (EV71) replication in EV71-infected-rhabdosarcoma (RD) cells. However, the specific mechanism by which RES-NPs prevent EV71 infection in RD cells remains largely unclear. The cell viability, inflammatory response, and oxidative stress in EV71-infected RD cells were assessed. Inhibition of protein kinase RNA-like endoplasmic reticulum kinase (PERK) significantly increased the viability of infected RD cells, reduced inflammation and oxidative stress, and led to a significant decrease in EV71 mRNA levels. Furthermore, treatment of infected RD cells with RES-NPs significantly increased cell viability and alleviated inflammation and oxidative stress, and these effects were further enhanced by inhibition of PERK. RES-NP treatment also resulted in a decrease in phosphorylated PERK, phosphorylated eukaryotic translation initiation factor 2α (eIF2α), and activating transcription factor 4 (ATF4) levels in infected RD cells, and the levels of these protein were further reduced by treatment with the PERK inhibitor. RES-NPs were found to inhibit EV71 infection by reducing virus-induced inflammatory responses and oxidative stress in RD cells, possibly through inactivation of the PERK-eIF2α-ATF4 signaling pathway.
已发现负载白藜芦醇的纳米颗粒（RES-NPs）可减少肠道病毒71型（EV71）在受EV71感染的横纹肌肉瘤（RD）细胞中的复制。然而，RES-NPs预防RD细胞中EV71感染的具体机制仍不清楚。评估了EV71感染的RD细胞中的细胞活力、炎症反应和氧化应激。抑制蛋白激酶RNA样内质网激酶（PERK）可显著提高受感染RD细胞的活力，减轻炎症和氧化应激，并导致EV71 mRNA水平显著降低。此外，用RES-NPs处理受感染的RD细胞可显著提高细胞活力，减轻炎症和氧化应激，而抑制PERK可进一步增强这些作用。RES-NP处理还导致受感染RD细胞中磷酸化PERK、磷酸化真核翻译起始因子2α（eIF2α）和激活转录因子4（ATF4）水平降低，用PERK抑制剂处理可进一步降低这些蛋白质的水平。研究发现，RES-NPs可能通过使PERK-eIF2α-ATF4信号通路失活，减少病毒诱导的RD细胞炎症反应和氧化应激，从而抑制EV71感染。
