Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infection in infants, children, immunocompromised adults, and elderly individuals. Currently, there are few therapeutic options available to prevent RSV infection. The present study aimed to investigate the effects of luteolin on RSV replication and the related mechanisms. We pretreated cells and mice with luteolin before infection with RSV, the virus titer, expressions of RSV-F, interferon (IFN)-stimulated genes (ISGs), and production of IFN-α and IFN-β were determined by plaque assay, RT-qPCR, and ELISA, respectively. The activation of Janus kinase (JAK)-signal transducer and activator of transcription 1 (STAT1) signaling pathway was detected by Western blotting and luciferase assay. Proteins which negatively regulate STAT1 were determined by Western blotting. Then cells were transfected with suppressor of cytokine signaling 1 (SOCS1) plasmid and virus replication and ISGs expression were determined. Luciferase reporter assay and Western blotting were performed to detect the relationship between SOCS1 and miR-155. Luteolin inhibited RSV replication, as shown by the decreased viral titer and RSV-F mRNA expression both in vitro and in vivo. The antiviral activity of luteolin was attributed to the enhanced phosphorylation of STAT1, resulting in the increased production of ISGs. Further study showed that SOCS1 was downregulated by luteolin and SOCS1 is a direct target of microRNA-155 (miR-155). Inhibition of miR-155 rescued luteolin-mediated SOCS1 downregulation, whereas upregulation of miR-155 enhanced the inhibitory effect of luteolin. Luteolin inhibits RSV replication by regulating the miR-155/SOCS1/STAT1 signaling pathway.

中文翻译：

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木犀草素通过调节 MiR-155/SOCS1/STAT1 信号通路抑制呼吸道合胞病毒复制

呼吸道合胞病毒 (RSV) 是婴儿、儿童、免疫功能低下的成人和老年人急性下呼吸道感染的主要原因。目前，可用于预防 RSV 感染的治疗选择很少。本研究旨在研究木犀草素对 RSV 复制的影响及相关机制。我们在感染 RSV 之前用木犀草素预处理细胞和小鼠，病毒滴度、RSV-F 的表达、干扰素 (IFN) 刺激的基因 (ISG) 以及 IFN-α 和 IFN-β 的产生通过斑块测定、RT 测定-qPCR 和 ELISA，分别。通过蛋白质印迹和荧光素酶测定检测 Janus 激酶 (JAK) 信号转导和转录激活因子 1 (STAT1) 信号通路的激活。通过蛋白质印迹确定负调节 STAT1 的蛋白质。然后用细胞因子信号抑制因子 1 (SOCS1) 质粒转染细胞，测定病毒复制和 ISGs 表达。进行荧光素酶报告基因测定和蛋白质印迹以检测 SOCS1 和 miR-155 之间的关系。木犀草素抑制 RSV 复制，如体外和体内病毒滴度和 RSV-F mRNA 表达降低所示。木犀草素的抗病毒活性归因于 STAT1 磷酸化的增强，导致 ISG 的产生增加。进一步的研究表明 SOCS1 被木犀草素下调，SOCS1 是 microRNA-155 (miR-155) 的直接靶标。miR-155 的抑制挽救了木犀草素介导的 SOCS1 下调，而 miR-155 的上调增强了木犀草素的抑制作用。