In:
The Natural Products Journal, Bentham Science Publishers Ltd., Vol. 13, No. 6 ( 2023-09)
Abstract:
Zika virus (ZIKV) infection is a public health concern and currently
there is no specific therapeutic or approved vaccine. Resveratrol (RESV), a natural antiviral compound, has been shown to possess antiviral properties against ZIKV and other viral infections,
but the mechanisms of action against ZIKV remain unknown. Objective: This study aimed to investigate the role of the high mobility group box 1 protein
(HMGB1) in the underlying anti-ZIKV mechanisms of RESV. Methods: HMGB1 protein expression and ZIKV replication in both the RESV-treated wildtype
(WT) and HMGB1-knockdown (shHMGB1) Huh7 cells were analyzed using ELISA, immunofluorescence assay, immunoblot assay, focus-forming assay and qRT-PCR. HMGB1’s
role was explored by evaluating the changes in the type-1 interferon (IFN) response genes using the qRT-PCR and immunoblot assays. Results: The treatment of the ZIKV-infected WT Huh7 cells with RESV significantly
reduced ZIKV titers by 〉 90% (P 〈 0.001) at 48 and 72 hr pi in a dose-dependent manner and
inhibited ZIKV-induced HMGB1 translocation (P 〈 0.001), resulting in nuclear HMGB1 accumulation.
Compared to the WT Huh7 cells, shHMGB1 Huh7 cells without RESV treatment showed a significant increase in the infectious virus titers and RNA with a maximum rise of
74% (P 〈 0.001) and 65% (P 〈 0.01), respectively. RESV treatment of the ZIKV-infected WT
Huh7 cells significantly increased the MxA (one of the classical interferon-stimulated genes, ISGs) and IFN-β levels (P 〈 0.05). The treatment of the infected shHMGB1 Huh7 cells with
RESV showed a less effective antiviral response (P 〉 0.05) and did not cause changes in the
expressions of MxA and IFN-β. Conclusion: RESV possesses therapeutic activity against ZIKV infection and the mechanism
of action is mainly attributed to HMGB1 nuclear retention, which could upregulate the type-1 IFN and ISGs.
Type of Medium:
Online Resource
ISSN:
2210-3155
DOI:
10.2174/2210315513666221114112253
Language:
English
Publisher:
Bentham Science Publishers Ltd.
Publication Date:
2023
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