The antiviral activity of myricetin against pseudorabies virus through regulation of the type I interferon signaling pathway

作者：Yizhen Song, Xufan Zhao, Yaqin Chen, Xingyue Yu, Tianli Su, Juan Wang, Tao He, Zhongqiong Yin, Renyong Jia, Xinghong Zhao, Xun Zhou, Lixia Li, Yuanfeng Zou, Mingyue Li, Dongmei Zhang, Yingying Zhang, Xu Song · 发表于：Journal of Virology · 年份：2024 · DOI：10.1128/jvi.01567-24 · 被引用次数：10 · 研究领域：Herpesvirus Infections and Treatments、interferon and immune responses、Virology and Viral Diseases

ABSTRACT The type I interferon signaling pathway constitutes a pivotal component of the innate immune response, encompassing the cGAS/STING and JAK/STAT pathways. Drugs that affect the body’s innate immune response could potentially be used as broad-spectrum antivirals. In this study, the antiviral activities of 25 flavonoids against pseudorabies virus (PRV) were tested in PK-15 cells. Eight active flavonoids were identified, with IC 50 values ranging from 23.24 to 323.09 µM. Subsequently, the regulatory effects of these flavonoids on the cGAS/STING pathway in PRV-infected cells were investigated. It was found that Myricetin significantly increased the transcriptional levels of cGAS , STING , IRF3 , and IFN-β , which had been reduced by PRV infection. The regulation of the type I in terferon signaling pathways by myricetin following PRV infection was further investigated through the production of cGAMP and the assessment of transcriptional and protein levels of pivotal genes and proteins. To confirm the activation of the innate immune response, a dual luciferase gene reporter study found that the expression of the IFN-β promoter in the myricetin-treated group was significantly elevated in a cellular model of type I interferon signaling pathway, and the contents of IFN-β were also significantly higher than those observed in the infected-untreated group in a PRV-infected mice model. Moreover, the transcriptional and protein levels of key genes and proteins in cell and mouse mod...