Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Fisetin Modulates Toll-Like Receptor-Mediated Innate Antiviral Response in Chikungunya Virus-Infected Hepatocellular Carcinoma Huh7 Cells

Version 1 : Received: 27 September 2022 / Approved: 28 September 2022 / Online: 28 September 2022 (12:15:36 CEST)

A peer-reviewed article of this Preprint also exists.

Lani, R.; Teoh, B.-T.; Sam, S.-S.; AbuBakar, S.; Hassandarvish, P. Fisetin Modulates Toll-like Receptor-Mediated Innate Antiviral Response in Chikungunya Virus-Infected Hepatocellular Carcinoma Huh7 Cells. Immuno 2022, 2, 703-719. Lani, R.; Teoh, B.-T.; Sam, S.-S.; AbuBakar, S.; Hassandarvish, P. Fisetin Modulates Toll-like Receptor-Mediated Innate Antiviral Response in Chikungunya Virus-Infected Hepatocellular Carcinoma Huh7 Cells. Immuno 2022, 2, 703-719.

Abstract

In the chronic phase of chikungunya virus (CHIKV) infection, excessive inflammation manifests as incapacitating joint pain and prolonged arthritis. Arthritis resulted from a large influx of infiltrating immune cells driven by pro-inflammatory cytokines and chemokines originating from the toll-like receptor (TLR)-mediated innate antiviral response. This study investigated fisetin's ability to modulate TLR-mediated antiviral responses against CHIKV in Huh7 cells. The CHIKV inhibitory potential of fisetin was assessed by plaque-forming unit assay, virus yield reduction assay, and bright-field microscopy (cytopathic effect, immunofluorescence). Fisetin’s modulatory potential on TLR-mediated antiviral response was evaluated by immunofluorescence assay (expression of TLR proteins), qRT-PCR (mRNA level of antiviral genes), human cytokine array, and immunoblotting of key transcription factors. The present study showed fisetin induced the expression of the antiviral genes at an early time-point by promoting the phosphorylation of IRF3 and IRF7. Fisetin reduced excessive inflammatory cytokine responses in CHIKV-infected Huh7 cells by impeding the over-phosphorylation of NF-κB. Fisetin also reduced CHIKV-induced cytopathic effects in CHIKV-infected Huh7 cells. Altogether, our study suggests that fisetin modulates TLR-mediated antiviral responses by affecting the CHIKV-induced inflammatory responses.

Keywords

infectious diseases; chikungunya; antiviral; flavonoids; fisetin; toll-like receptors

Subject

Medicine and Pharmacology, Medicine and Pharmacology

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