奥米克朗亚型BA.5有效地感染肺细胞
Markus Hoffmann1,2, Lok-Yin Roy Wong3, Prerna Arora4,5
1Infection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, Göttingen, Germany. mhoffmann@dpz.eu.
Nature communications
|June 13, 2023
概括
欧米克朗BA.5亚变体有效地感染肺细胞,与早期的欧米克朗变体不同. 这种增加的肺细胞进入表明在SARS-CoV-2进化中潜在的减弱损失.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 传染性疾病 传染性疾病
背景情况:
- 与早期变种相比,SARS-CoV-2 Omicron亚型BA.1和BA.2显示肺细胞感染减少,与较低的致病性相关.
- 在肺细胞感染方面,继承BA.1和BA.2的BA.5亚变体的传染性和致病性仍然不清楚.
研究的目的:
- 调查SARS-CoV-2 Omicron BA.5亚变体是否保留了在BA.1和BA.2中观察到的减弱肺细胞感染表型.
- 确定BA.5肺细胞进入和复制效率背后的分子机制.
主要方法:
- 对BA.5与BA.1和BA.2的S1/S2部位的尖端 (S) 蛋白分裂的比较分析.
- 通过BA.5 S蛋白质介导的细胞融合和肺细胞进入效率的评估.
- 在培养的人类肺细胞中评估BA.5复制.
- 在雌性Balb/c小鼠的肺部和雌性的鼻腔中BA.5复制的体内研究.
主要成果:
- 与BA.1和BA.2相比,BA.5尖端蛋白显示S1/S2位点裂变的增加以及在驱动细胞-细胞融合和肺细胞进入方面提高效率.
- 鉴定出H69Δ/V70Δ突变对于BA.5.5.中观察到的肺细胞进入增加至关重要.
- 与BA.1.相比,BA.5在培养的肺细胞中表现出高效的复制,并且在小鼠和的肺部表现出明显更高的复制率.
结论:
- SARS-CoV-2 Omicron BA.5 亚型已经恢复了有效感染肺细胞的能力,这是严重疾病的关键因素.
- 奥米克朗亚变体的演变可能导致衰减的部分逆转,BA.5显示出增加的致病性潜力.
- 这些发现突显了病毒进化的动态性质,以及新出现的SARS-CoV-2菌株中毒性增加的可能性.
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