Citation: Wenjing Zhu, Qi Li, Yong Yin, Huanchun Chen, Youhui Si, Bibo Zhu, Shengbo Cao, Zikai Zhao, Jing Ye. Ferroptosis contributes to JEV-induced neuronal damage and neuroinflammation .VIROLOGICA SINICA, 2024, 39(1) : 144-155.  http://dx.doi.org/10.1016/j.virs.2023.12.004

Ferroptosis contributes to JEV-induced neuronal damage and neuroinflammation

  • Ferroptosis is a newly discovered prototype of programmed cell death (PCD) driven by iron-dependent phospholipid peroxidation accumulation, and it has been linked to numerous organ injuries and degenerative pathologies. Although studies have shown that a variety of cell death processes contribute to JEV-induced neuroinflammation and neuronal injury, there is currently limited research on the specific involvement of ferroptosis. In this study, we explored the neuronal ferroptosis induced by JEV infection in vitro and in vivo. Our results indicated that JEV infection induces neuronal ferroptosis through inhibiting the function of the antioxidant system mediated by glutathione (GSH)/glutathione peroxidase 4 (GPX4), as well as by promoting lipid peroxidation mediated by yes-associated protein 1 (YAP1)/long-chain acyl-CoA synthetase 4 (ACSL4). Further analyses revealed that JEV E and prM proteins function as agonists, inducing ferroptosis. Moreover, we found that treatment with a ferroptosis inhibitor in JEV-infected mice reduces the viral titers and inflammation in the mouse brains, ultimately improving the survival rate of infected mice. In conclusion, our study unveils a critical role of ferroptosis in the pathogenesis of JEV, providing new ideas for the prevention and treatment of viral encephalitis.

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    Ferroptosis contributes to JEV-induced neuronal damage and neuroinflammation

      Corresponding author: Zikai Zhao, zkzhao@mail.hzau.edu.cn
      Corresponding author: Jing Ye, yej@mail.hzau.edu.cn
    • a. National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, 430070, China;
    • b. Frontiers Science Center for Animal Breeding and Sustainable Production, Huazhong Agricultural University, Wuhan, 430070, China;
    • c. The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, 430070, China;
    • d. Hubei Hongshan Laboratory, Wuhan, 430070, China

    Abstract: Ferroptosis is a newly discovered prototype of programmed cell death (PCD) driven by iron-dependent phospholipid peroxidation accumulation, and it has been linked to numerous organ injuries and degenerative pathologies. Although studies have shown that a variety of cell death processes contribute to JEV-induced neuroinflammation and neuronal injury, there is currently limited research on the specific involvement of ferroptosis. In this study, we explored the neuronal ferroptosis induced by JEV infection in vitro and in vivo. Our results indicated that JEV infection induces neuronal ferroptosis through inhibiting the function of the antioxidant system mediated by glutathione (GSH)/glutathione peroxidase 4 (GPX4), as well as by promoting lipid peroxidation mediated by yes-associated protein 1 (YAP1)/long-chain acyl-CoA synthetase 4 (ACSL4). Further analyses revealed that JEV E and prM proteins function as agonists, inducing ferroptosis. Moreover, we found that treatment with a ferroptosis inhibitor in JEV-infected mice reduces the viral titers and inflammation in the mouse brains, ultimately improving the survival rate of infected mice. In conclusion, our study unveils a critical role of ferroptosis in the pathogenesis of JEV, providing new ideas for the prevention and treatment of viral encephalitis.

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