Scholarlink

<p>Japanese encephalitis (JE), caused by the Japanese encephalitis virus (JEV), remains a major global health concern. A deeper understanding of how JEV manipulates host antiviral responses is critical for developing more effective therapeutic strategies. In this study, we identified a novel immune evasion mechanism through which JEV suppresses host innate immunity to facilitate viral replication. Specifically, JEV infection induces the expression of the host translation elongation factor TUFM by activating the transcription factor JUN. We demonstrated that TUFM promotes JEV replication, while TUFM silencing significantly reduces viral load. Mechanistically, TUFM acts as a scaffold to recruit the E3 ubiquitin ligase Parkin and the autophagy receptor p62, thereby mediating selective autophagy-dependent degradation of the key innate immune adaptor TRAF3. Intriguingly, the viral NS5 protein was also found to promote TRAF3 degradation via a similar autophagy-dependent pathway, suggesting a coordinated strategy between viral and host factors. Since TRAF3 is essential for the activation of IRF3 and downstream type I interferon signaling, its degradation effectively blunts antiviral innate immune responses. Collectively, our findings reveal a previously unrecognized mechanism by which JEV subverts host innate immunity through the TUFM-NS5-Parkin-p62-TRAF3 axis to promote immune evasion and viral propagation.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Japanese encephalitis virus degrades TRAF3 to suppress type I interferon and promote viral replication through NS5 and host TUFM proteins

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月4日

查看全文
  • Xingya Wang,
  • Chen Wang,
  • Xinyu Yang,
  • Wenzhen Qin,
  • Xuelan Liu,
  • Hai Yu,
  • Wu Tong,
  • Guangzhi Tong,
  • Tongling Shan,
  • Ning Kong,
  • Guangxu Xing,
  • Hao Zheng

摘要

Japanese encephalitis (JE), caused by the Japanese encephalitis virus (JEV), remains a major global health concern. A deeper understanding of how JEV manipulates host antiviral responses is critical for developing more effective therapeutic strategies. In this study, we identified a novel immune evasion mechanism through which JEV suppresses host innate immunity to facilitate viral replication. Specifically, JEV infection induces the expression of the host translation elongation factor TUFM by activating the transcription factor JUN. We demonstrated that TUFM promotes JEV replication, while TUFM silencing significantly reduces viral load. Mechanistically, TUFM acts as a scaffold to recruit the E3 ubiquitin ligase Parkin and the autophagy receptor p62, thereby mediating selective autophagy-dependent degradation of the key innate immune adaptor TRAF3. Intriguingly, the viral NS5 protein was also found to promote TRAF3 degradation via a similar autophagy-dependent pathway, suggesting a coordinated strategy between viral and host factors. Since TRAF3 is essential for the activation of IRF3 and downstream type I interferon signaling, its degradation effectively blunts antiviral innate immune responses. Collectively, our findings reveal a previously unrecognized mechanism by which JEV subverts host innate immunity through the TUFM-NS5-Parkin-p62-TRAF3 axis to promote immune evasion and viral propagation.