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Updated: Jul 22, 2025
A Murine Model of Dengue Virus-induced Acute Viral Encephalitis-like Disease
Published on: April 28, 2019
H3K27me3 of Rnf19a promotes neuroinflammatory response during Japanese encephalitis virus infection
Shuo Zhu1,2,3, Mengying Tao1,2,3, Yunchuan Li1,2,3
1National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, 430070, Hubei, China.
Abstract:
Histone methylation is an important epigenetic modification that affects various biological processes, including the inflammatory response. In this study, we found that infection with Japanese encephalitis virus (JEV) leads to an increase in H3K27me3 in BV2 microglial cell line, primary mouse microglia and mouse brain. Inhibition of H3K27me3 modification through EZH2 knockdown and treatment with EZH2 inhibitor significantly reduces the production of pro-inflammatory cytokines during JEV infection, which suggests that H3K27me3 modification plays a crucial role in the neuroinflammatory response caused by JEV infection. The chromatin immunoprecipitation-sequencing (ChIP-sequencing) assay revealed an increase in H3K27me3 modification of E3 ubiquitin ligases Rnf19a following JEV infection, which leads to downregulation of Rnf19a expression. Furthermore, the results showed that Rnf19a negatively regulates the neuroinflammatory response induced by JEV. This is achieved through the degradation of RIG-I by mediating its ubiquitination. In conclusion, our findings reveal a novel mechanism by which JEV triggers extensive neuroinflammation from an epigenetic perspective.
Insights
Japanese encephalitis virus (JEV) infection increases histone methylation (H3K27me3), driving neuroinflammation. Inhibiting this epigenetic modification reduces inflammatory cytokines and reveals Rnf19a as a key regulator in JEV-induced brain inflammation.
Area of Science:
- Epigenetics
- Neuroimmunology
- Virology
Background:
- Histone methylation is a key epigenetic mechanism influencing biological processes, including inflammation.
- Neuroinflammation is a complex response implicated in various neurological disorders.
- Japanese encephalitis virus (JEV) is a significant cause of viral encephalitis globally.
Purpose of the Study:
- To investigate the role of histone methylation, specifically H3K27me3, in JEV-induced neuroinflammation.
- To elucidate the molecular mechanisms linking H3K27me3 modification to inflammatory responses during JEV infection.
- To identify potential therapeutic targets for mitigating JEV-associated neuroinflammation.
Main Methods:
- Analysis of H3K27me3 levels in microglial cell lines, primary microglia, and mouse brains following JEV infection.
- Utilized EZH2 knockdown and inhibitors to assess the impact of H3K27me3 inhibition on cytokine production.
- Employed chromatin immunoprecipitation-sequencing (ChIP-sequencing) to identify genes targeted by H3K27me3.
- Investigated the role of Rnf19a in JEV infection and its mechanism involving RIG-I ubiquitination and degradation.
Main Results:
- JEV infection significantly increased H3K27me3 levels in microglial cells and mouse brains.
- Inhibition of H3K27me3 via EZH2 modulation markedly reduced pro-inflammatory cytokine production during JEV infection.
- ChIP-sequencing identified Rnf19a as a target of increased H3K27me3, leading to its downregulation.
- Rnf19a was found to negatively regulate JEV-induced neuroinflammation by promoting RIG-I degradation through ubiquitination.
Conclusions:
- H3K27me3 modification plays a critical role in mediating JEV-induced neuroinflammation.
- The epigenetic regulation of Rnf19a by H3K27me3 is a novel mechanism contributing to JEV pathogenesis.
- Targeting H3K27me3 or Rnf19a may offer therapeutic strategies against JEV-induced brain inflammation.
