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<p>Herpes simplex virus type I (HSV-1) infection is associated with lung injury; however, no specific treatment is currently available. In this study, we found a significant negative correlation between FcRn levels and the severity of HSV-1-induced lung injury. HSV-1 infection increases the methylation of the FcRn promoter, which suppresses FcRn expression by upregulating DNMT3b expression. Analysis of the FcRn promoter revealed that the -1296- to -919-bp region is the key regulatory region, with the CG site at -967/-966&#xa0;bp being the critical methylation site. The transcription factor JUN binds to this CG site to increase FcRn transcription; however, its activity was significantly inhibited by DNMT3b overexpression. Moreover, 5-Aza-2 effectively reduced HSV-1-induced lung injury and inhibited ferroptosis. Transcriptomic sequencing revealed that the ferroptosis pathway was highly activated in the lung tissues of FcRn-knockout mice via the p53/SLC7A11 pathway. Furthermore, in vivo and in vivo experiments showed that FcRn knockout aggravated lung epithelial cell inflammation by promoting ferroptosis; however, this effect was reversed by a ferroptosis inhibitor. Thus, HSV-1 infection suppressed FcRn expression through promoter methylation and promoted ferroptosis and lung injury. These findings reveal a novel molecular mechanism underlying viral lung injury and suggest potential therapeutic strategies for targeting FcRn.</p> Graphical Abstract <p></p>

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Downregulation of FcRn promotes ferroptosis in herpes simplex virus-1-induced lung injury

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年1月6日

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  • Shaoju Qian,
  • Danqiong Zhang,
  • Ruixue Li,
  • Xiaoming Sha,
  • Shuao Lu,
  • Lin Pan,
  • Xianfeng Hui,
  • Tiesuo Zhao,
  • Xiangfeng Song,
  • Lili Yu

摘要

Herpes simplex virus type I (HSV-1) infection is associated with lung injury; however, no specific treatment is currently available. In this study, we found a significant negative correlation between FcRn levels and the severity of HSV-1-induced lung injury. HSV-1 infection increases the methylation of the FcRn promoter, which suppresses FcRn expression by upregulating DNMT3b expression. Analysis of the FcRn promoter revealed that the -1296- to -919-bp region is the key regulatory region, with the CG site at -967/-966 bp being the critical methylation site. The transcription factor JUN binds to this CG site to increase FcRn transcription; however, its activity was significantly inhibited by DNMT3b overexpression. Moreover, 5-Aza-2 effectively reduced HSV-1-induced lung injury and inhibited ferroptosis. Transcriptomic sequencing revealed that the ferroptosis pathway was highly activated in the lung tissues of FcRn-knockout mice via the p53/SLC7A11 pathway. Furthermore, in vivo and in vivo experiments showed that FcRn knockout aggravated lung epithelial cell inflammation by promoting ferroptosis; however, this effect was reversed by a ferroptosis inhibitor. Thus, HSV-1 infection suppressed FcRn expression through promoter methylation and promoted ferroptosis and lung injury. These findings reveal a novel molecular mechanism underlying viral lung injury and suggest potential therapeutic strategies for targeting FcRn.

Graphical Abstract