Methionine enkephalin upregulates Toll-like receptors in macrophages to suppress severe fever with thrombocytopenia syndrome virus infection

SFTSV-infected RAW264.7 macrophage model pretreated with MENK was established, and RNA sequencing was employed to analyze transcriptomic alterations and differentially expressed genes (DEGs). Based on bioinformatics analysis, subsequent experimental validation was performed on key DEGs, including TLR7, TLR3, TLR8, TLR9, AP-1, IL-17RA, TNF-Alpha, IL-1Beta, CCR5, and CXCL10. MENK upregulated the expression levels of the pattern recognition receptors and cytokine receptors; promoted the nuclear transcription to modulate cellular immune responses; and increased the levels of the cytokines to induce inflammatory responses against SFTSV infection. Notably, MENK possessed unique advantages and exhibited efficacy comparable to IMQ in restoring antiviral immunity, suggested that MENK emerged as a promising host-directed therapeutic candidate or vaccine prototype against SFTSV infection, warranting further preclinical and clinical investigation.