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Recently, the international academic journal mBio published online the "Herpes Simplex Virus 1-Induced Ferroptosis Contributes to Viral Encephalitis" entitled "Herpes Simplex Virus 1-Induced Ferroptosis Contributes to Viral Encephalitis" by the team of Zhou Xi/Qiu Yang of Wuhan Institute of Virology/State Key Laboratory of Virology, Chinese Academy of Sciences, Xu Yi team of Guangzhou Women and Children Medical Center, and Lin Shuhai team of Xiamen University (https://journals.
asm.
org/doi/10.
1128/mbio.
02370-22) Collaborative research results
.
This study is the first to demonstrate that herpes simplex virus type 1 (HSV-1) can induce ferrozois and reveal the molecular mechanism of HSV-1-induced ferrozois and the role of
ferrozosis in viral encephalitis.
asm.
org/doi/10.
1128/mbio.
02370-22) Collaborative research results
.
This study is the first to demonstrate that herpes simplex virus type 1 (HSV-1) can induce ferrozois and reveal the molecular mechanism of HSV-1-induced ferrozois and the role of
ferrozosis in viral encephalitis.
Siderophosis is a non-apoptotic form of programmed cell death that relies on iron-mediated formation and accumulation
of lipid radicals.
In this study, the research team found that HSV-1 can detect specific indicators of hemozosis after infecting human glial cells and mouse brain tissue, thereby proving that HSV-1 can induce hemozoosis; It was also found that HSV-1 inhibits downstream antioxidant genes by degrading Nrf2 protein, thereby disturbing cellular redox homeostasis and promoting the mechanism
of iron zoosis.
The research team further explored the molecular mechanism of HSV-1 inhibition of Nrf2, and found that HSV-1 degrades Nrf2 expression through the ubiquitination-proteasome pathway, and its ubiquitination pathway depends on Keap1 protein, and determined that this ubiquitination type is K48 ubiquitination
.
of lipid radicals.
In this study, the research team found that HSV-1 can detect specific indicators of hemozosis after infecting human glial cells and mouse brain tissue, thereby proving that HSV-1 can induce hemozoosis; It was also found that HSV-1 inhibits downstream antioxidant genes by degrading Nrf2 protein, thereby disturbing cellular redox homeostasis and promoting the mechanism
of iron zoosis.
The research team further explored the molecular mechanism of HSV-1 inhibition of Nrf2, and found that HSV-1 degrades Nrf2 expression through the ubiquitination-proteasome pathway, and its ubiquitination pathway depends on Keap1 protein, and determined that this ubiquitination type is K48 ubiquitination
.
In addition, the research team determined that HSV-1-induced ferrozosis is closely related to the occurrence of viral encephalitis in HSV-1 mouse encephalitis models, and the use of ferrozotic inhibitor (Fer-1) or proteasome inhibitor (MG132) to inhibit Nrf2 expression can effectively inhibit the occurrence of HSV-1 encephalitis; At the same time, the mechanism of hemozosis causing HSV-1 encephalitis is to activate the PTGS2/PGE2 pathway, and the use of PTGS2 inhibitors (INDs) can effectively inhibit the expression
of various inflammatory factors caused by HSV-1.
In summary, this study elucidates the molecular mechanism of HSV-1-induced iron zoitis and provides new insights
into the pathogenesis of HSV-1 encephalitis.
of various inflammatory factors caused by HSV-1.
In summary, this study elucidates the molecular mechanism of HSV-1-induced iron zoitis and provides new insights
into the pathogenesis of HSV-1 encephalitis.
Researcher Zhou Xi and Qiu Yang of Wuhan Institute of Virology, Chinese Academy of Sciences, Professor Xu Yi of Guangzhou Women and Children's Medical Center, and Professor Lin Shuhai of School of Life Sciences, Xiamen University are co-corresponding authors of the paper.
Dr.
Xu Xiqiu, a joint postdoctoral fellow of the Wuhan Institute of Virology, Chinese Academy of Sciences-Guangzhou Women and Children's Medical Center, and Dr.
Tongran Xu of Xiamen University are co-first authors
of the paper.
Dr.
Xu Xiqiu, a joint postdoctoral fellow of the Wuhan Institute of Virology, Chinese Academy of Sciences-Guangzhou Women and Children's Medical Center, and Dr.
Tongran Xu of Xiamen University are co-first authors
of the paper.
Study on the mechanism of HSV-1-induced iron death leading to viral encephalitis