Attenuated replication and pathogenicity of SARS-CoV-2 B.1.1.529 Omicron
Attenuated replication and pathogenicity of SARS-CoV-2 B.1.1.529 Omicron
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DOI：
10.1038/s41586-022-04442-5
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发表时间：
2022-01-21
期刊：
影响因子：
64.8
通讯作者：
Chu, Hin
中科院分区：
文献类型：
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作者：
Shuai, Huiping;Chan, Jasper Fuk-Woo;Chu, Hin
SARS-CoV-2的Omicron(B.1.1.529)变种于2021年11月出现，并在人类中迅速传播(1)。尽管最近的报告显示，奥米克龙变种可以很好地逃脱疫苗相关和治疗性中和抗体(2-10)，但病毒的致病性仍不清楚。在这里，我们显示奥米克隆的复制在人的Calu3和Caco 2细胞中显著减弱。进一步的机制研究表明，与野生型SARS-CoV-2(HKU-001A)和以前的变异体相比，Omicron在使用跨膜丝氨酸蛋白酶2(TMPRSS2)方面效率低下，这可能是其在Calu3和Caco 2细胞中复制减少的原因。与野生型和Delta(B.1.617.2)变异体相比，感染K18-hACE2小鼠的上呼吸道和下呼吸道中Omicron的复制明显减弱，导致其肺部病理显著改善。与野生型SARS-CoV-2和Alpha(B.1.1.7)、Beta(1.351)和Delta变种相比，感染Omicron导致的体重下降和死亡率最低。总体而言，我们的研究表明，与野生型毒株和其他变种相比，SARS-CoV-2的欧米克龙变种在小鼠中的复制和致病性减弱。
The Omicron (B.1.1.529) variant of SARS-CoV-2 emerged in November 2021 and is rapidly spreading among the human population(1). Although recent reports reveal that the Omicron variant robustly escapes vaccine-associated and therapeutic neutralization antibodies(2-10), the pathogenicity of the virus remains unknown. Here we show that the replication of Omicron is substantially attenuated in human Calu3 and Caco2 cells. Further mechanistic investigations reveal that Omicron is inefficient in its use of transmembrane serine protease 2 (TMPRSS2) compared with wild-type SARS-CoV-2 (HKU-001a) and previous variants, which may explain its reduced replication in Calu3 and Caco2 cells. The replication of Omicron is markedly attenuated in both the upper and lower respiratory tracts of infected K18-hACE2 mice compared with that of the wild-type strain and Delta (B.1.617.2) variant, resulting in its substantially ameliorated lung pathology. Compared with wild-type SARS-CoV-2 and the Alpha (B.1.1.7), Beta (1.351) and Delta variants, infection by Omicron causes the lowest reduction in body weight and the lowest mortality rate. Overall, our study demonstrates that the replication and pathogenicity of the Omicron variant of SARS-CoV-2 in mice is attenuated compared with the wild-type strain and other variants.