通过IL11信号传递,SARS-CoV-2辅助蛋白参与炎症和益纤维化过程
Blanca D López-Ayllón1, Ana de Lucas-Rius1, Laura Mendoza-García1
1Molecular Biomedicine Department, Margarita Salas Center for Biological Research (CIB-CSIC), Madrid, Spain.
Frontiers in immunology
|August 7, 2023
概括
在SARS-CoV-2中,辅助蛋白ORF6,ORF8,ORF9b和ORF9c可对WNT5A和IL11进行上调,促进炎症和纤维化. 这些蛋白质是COVID-19治疗的潜在治疗点.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 肺部病理学 肺部病理学
背景情况:
- 严重急性呼吸系统综合征冠状病毒2 (SARS-CoV-2) 具有11种辅助蛋白质,在感染期间的作用尚不完全理解.
- 随着COVID-19的流行,人们需要了解病毒病原和宿主反应.
研究的目的:
- 研究SARS-CoV-2辅助蛋白在宿主细胞反应中的作用,特别关注炎症和纤维化.
- 为了确定COVID-19的潜在治疗点.
主要方法:
- 对表达单个SARS-CoV-2辅助蛋白质 (ORF6,ORF8,ORF9b,ORF9c) 的A549细胞进行转录分析.
- 生物信息学分析以确定途径和疾病关联.
- 功能性测试以确认亲纤维细胞的反应.
- 结果与SARS-CoV-2感染肺细胞和COVID-19患者肺部活检的数据进行比较.
主要成果:
- 在表达SARS-CoV-2辅助蛋白ORF6,ORF8,ORF9b和ORF9c的细胞中,WNT5A和IL11的上调.
- 与IL11信号相关的基因被差异地表达.
- WNT5A和IL11涉及异常性肺纤维化和亲纤维化反应.
- 在这项研究中,改变的profibrotic基因表达与SARS-CoV-2感染的肺细胞和COVID-19患者活检中的发现相匹配.
结论:
- 在SARS-CoV-2中,辅助蛋白ORF6,ORF8,ORF9b和ORF9c都参与了炎症和亲纤维性反应.
- 这些辅助蛋白质代表了新型COVID-19治疗的潜在治疗点.
- 了解这些病毒与宿主之间的相互作用对于开发针对COVID-19的有效疗法至关重要.
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