SARS-CoV-2 Omicron variant replication in human bronchus and lung ex vivo
SARS-CoV-2 Omicron variant replication in human bronchus and lung ex vivo
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DOI：
10.1038/s41586-022-04479-6
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发表时间：
2022-02-01
期刊：
影响因子：
64.8
通讯作者：
Chan, Michael C. W.
中科院分区：
文献类型：
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作者：
Hui, Kenrie P. Y.;Ho, John C. W.;Chan, Michael C. W.
出现令人担忧的SARS-CoV-2变种，并逐渐增加人与人之间的传播率，对全球公共卫生构成威胁。SARS-CoV-2的Omicron变种也可以逃避自然感染或疫苗的免疫(1)，但尚不清楚其特殊的传播性是由于免疫逃避还是固有的病毒学特性。在此，我们比较了野生型病毒和D614G、Alpha(B.1.1.7)、Beta(B.1.351)、Delta(B.1.617.2)和Omicron(B.1.1.529)变异株在人支气管和肺的体外培养中的复制能力和细胞趋向性。我们还评估了TMPRSS2和组织蛋白酶对感染的依赖性。我们发现，Omicron的复制速度比所有其他SARS-CoV-2变种在支气管中的复制速度快，但在肺实质中的复制效率较低。与野生型相比，所有受关注的变种都有类似的细胞趋向性。Omicron比测试的其他变种更依赖组织蛋白酶，这表明与其他变种相比，Omicron变种通过不同的途径进入细胞。Omicron在人类肺部的复制能力较低，这可能解释了流行病学研究中报告的Omicron严重程度降低的原因，尽管严重程度的决定因素是多因素的。这些发现为先前的流行病学观察提供了重要的生物学关联。
The emergence of SARS-CoV-2 variants of concern with progressively increased transmissibility between humans is a threat to global public health. The Omicron variant of SARS-CoV-2 also evades immunity from natural infection or vaccines(1), but it is unclear whether its exceptional transmissibility is due to immune evasion or intrinsic virological properties. Here we compared the replication competence and cellular tropism of the wild-type virus and the D614G, Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2) and Omicron (B.1.1.529) variants in ex vivo explant cultures of human bronchi and lungs. We also evaluated the dependence on TMPRSS2 and cathepsins for infection. We show that Omicron replicates faster than all other SARS-CoV-2 variants studied in the bronchi but less efficiently in the lung parenchyma. All variants of concern have similar cellular tropism compared to the wild type. Omicron is more dependent on cathepsins than the other variants of concern tested, suggesting that the Omicron variant enters cells through a different route compared with the other variants. The lower replication competence of Omicron in the human lungs may explain the reduced severity of Omicron that is now being reported in epidemiological studies, although determinants of severity are multifactorial. These findings provide important biological correlates to previous epidemiological observations.