Luteolin Inhibits Respiratory Syncytial Virus Replication by Regulating the MiR-155/SOCS1/STAT1 Signaling Pathway

Abstract

Background 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. Material and methods We pretreated cells and mice with luteolin before infection with RSV, the virus titer, expressions of interferon (IFN)-stimulated genes (ISGs), RSV-F and production of IFN-α and IFN-β were determined by plaque assay, RT-qPCR and ELISA. 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 regulates STAT1 was determined by Western blotting. Then cells were transfected with suppressor of cytokine signaling 1 (SOCS1) plasmid and virus replication and ISGs expression was determined. Luciferase reporter assay and Western blotting was performed to detect the relationship between SOCS1 and miR-155. Results 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. Conclusion Luteolin inhibits RSV replication by regulating the miR-155/SOCS1/STAT1 signaling pathway.

Molecular Mechanism of Jinchan Oral Liquid in the Treatment of Children with Respiratory Syncytial Virus Pneumonia Based on Network Pharmacology and Molecular Docking Technology

“…Luteolin is a typical flavonoid compound and has been widely studied for its effects, including antioxidant, anticancer, anti-inflammatory, and antiapoptotic [19]. Wang et al found that luteolin can decrease the titer of RSV and inhibit viral replication [20]. Kaempferol, known as polyphenol, was a flavonol present in different plants.…”