移植性SARS-CoV-2蛋白ORF8与补充C1q结合,从而引发胎儿炎症
Tamiris Azamor1, Débora Familiar-Macedo1, Gielenny M Salem1
1Infection Biology Program, Global Center for Pathogen Research and Human Health, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
The EMBO journal
|October 10, 2024
概括
产前COVID-19感染会通过SARS-CoV-2ORF8蛋白结合引发炎症,以补充C1q. 这一途径有助于胎儿炎症,即使没有直接的胎儿病毒暴露.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 产科 产科 产科 产科 产科
背景情况:
- 产前的SARS-CoV-2感染与不良的怀孕和分娩结果有关.
- 垂直传播被认为是低的,但观察到胎儿炎症.
研究的目的:
- 调查胎儿炎症在怀孕期间与产前SARS-CoV-2感染的机制.
- 确定特定的病毒蛋白和宿主因子,参与胎盘和胎儿炎症.
主要方法:
- 来自23个COVID-19母婴对的胎盘,带和羊水样本的多组分析.
- 在胎儿组织中检测SARS-CoV-2RNA和蛋白质 (ORF8).
- 在体外研究中,使用暴露于ORF8.8的人类胎盘 trofhoblasts.
- 共同免疫沉以确定蛋白质相互作用.
主要成果:
- 强大的炎症反应和补充蛋白质表达 (C1q,C3,C4,C5) 在胎儿区.
- 在超过60%的胎儿组织中检测到SARS-CoV-2ORF8蛋白,与炎症增加和补体激活相关.
- 外源ORF8暴露诱导了胎盘细胞中的补体激活和炎症.
- ORF8通过特定的区直接结合补充C1q.
结论:
- 一种新的ORF8-C1q-依赖补充激活通路有助于胎儿在产前COVID-19中的炎症.
- 这种途径可能会调解胎儿炎症,而不依赖于直接的胎儿SARS-CoV-2感染.
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