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 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. 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.

TRIM22. A Multitasking Antiviral Factor

“…The evidence of TRIM22 antiviral activity against RSV is founded on in vitro infection of permissive cells in which TRIM22 expression was downregulated by RNA interference. An increase in viral RNA expression was detected in TRIM22 knocked-down cells, as compared to control cells [108]. However, the mechanism of RSV restriction by TRIM22 remains to be elucidated.…”

“…Very recently, a report has shown that TRIM22 exerts an inhibitory activity on respiratory syncytial virus (RSV) [108]. RSV is a negative single-stranded RNA virus that belongs to the family of paramyxoviridae.…”

Integrated Network Pharmacology and Lipidomics to Reveal the Inhibitory Effect of Qingfei Oral Liquid on Excessive Autophagy in RSV-Induced Lung Inflammation

“…In terms of chemical properties, most ingredients were identified as flavonoids, natural polyphenols with presumed beneficial effects on anti-inflammation, antioxidation, and immunomodulation ( Yi, 2018 ; Zeng et al, 2019 ). Previous findings confirmed that the main flavone constituents in QF, such as Quercetin and Luteolin, could inhibit RSV replication by directly blocking viral adhesion or modulating microRNA-related signaling pathways ( Wang S. et al, 2020 ; Lopes et al, 2020 ). Although there was no literature reporting direct links between RSV and Kaempferol, Naringenin, or Isorhamnetin, these compounds are reported to play critical roles in antiviral and anti-inflammatory procedures by reducing viral replication, inhibiting inflammatory cytokines, and eliminating free radicals in respiratory tract viral diseases ( Yang et al, 2019 ; Huang YF.…”

5-Hydroxymethylfurfural Enhances the Antiviral Immune Response in Macrophages through the Modulation of RIG-I-Mediated Interferon Production and the JAK/STAT Signaling Pathway

“…Wang et al reported that luteolin, a common bioflavonoid found in fruits and vegetables, increased the production of ISGs by enhancing STAT1 phosphorylation, resulting in an inhibition of RSV replication. 38 Kawaguchi et al reported that the bioactive constituent tryptanthrin, found in the indigo plants Polygonum tinctrorium and Isatis tinctoria, altered STAT1 phosphorylation and nuclear translocation in HU-VECs. 39 In the present study, we found that compared to that of the untreated group, the expression levels of If it1, If it2, Isg15, and Ccl5 mRNA in the 5-HMF-treated macrophages infected with VSV were significantly upregulated (Figure 3).…”