AI Article Synopsis
- HSV-1 infection can lead to lung injury, and a study found that lower levels of FcRn (a protein) are linked to more severe lung damage caused by the virus.
- The study revealed that HSV-1 increases the methylation of the FcRn gene, which reduces its expression by promoting DNMT3b, a protein that inhibits transcription through a specific region of the FcRn promoter.
- Inhibiting ferroptosis (a type of cell death) with a drug helped reduce lung injury in cases affected by HSV-1, indicating that targeting FcRn might be a promising therapeutic approach.
Article Abstract
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.
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| http://dx.doi.org/10.1007/s00018-024-05555-y | DOI Listing |
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