Japanese encephalitis virus-induced DNA methylation contributes to blood-brain barrier permeability by modulating tight junction protein expression
文献类型： 外文期刊
第一作者： Xiang, Xiao
作者： Xiang, Xiao;Yu, Du;Li, Zhuangzhuang;Wei, Jianchao;Liu, Ke;Li, Zongjie;Shao, Donghua;Li, Beibei;Ma, Zhiyong;Qiu, Yafeng;Xiang, Xiao;Fros, Jelke J.;Kortekaas, Jeroen;van Oers, Monique M.;Pijlman, Gorben P.
作者机构：
关键词：
Japanese encephalitis virus; DNA methylation; WGBS; Blood-brain barrier;
期刊名称：JOURNAL OF NEUROINFLAMMATION （ 影响因子：10.1； 五年影响因子：10.9 ）
ISSN：
年卷期： 2024 年 21 卷 1 期
页码：
收录情况： SCI
摘要： Japanese encephalitis virus (JEV) is a neurotropic and neuroinvasive flavivirus causing viral encephalitis, which seriously threatens the development of animal husbandry and human health. DNA methylation is a major epigenetic modification involved in viral pathogenesis, yet how DNA methylation affects JEV infection remains unknown. Here, we show genome-wide DNA methylation profiles in the brains of JEV-infected mice compared to mock-infected mice. JEV can significantly increase the overall DNA methylation levels in JEV-infected mouse brains. A total of 14,781 differentially methylated regions associated genes (DMGs) have been identified. Subsequently, KEGG pathway analysis suggested that DNA methylation modulates the tight junction signaling pathway, which can potentially impact the permeability of the blood-brain barrier (BBB). We demonstrate that hypermethylation of the tight junction gene Afdn promoter inhibited AFDN expression and increased monolayer permeability of mouse brain microvascular endothelial (bEnd.3) cells in an in vitro transwell assay. Collectively, this study reveals that DNA methylation is increased in a murine Japanese encephalitis model and that modulation of Afdn expression promotes BBB permeability.
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