SARS-CoV-2 Omicron variant shows less efficient replication and fusion activity when compared with Delta variant in TMPRSS2-expressed cells.
SARS-CoV-2 Omicron variant shows less efficient replication and fusion activity when compared with Delta variant in TMPRSS2-expressed cells.
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DOI：
10.1080/22221751.2021.2023329
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发表时间：
2022-12
影响因子：
13.2
通讯作者：
To KK
中科院分区：
文献类型：
--
作者：
Zhao H;Lu L;Peng Z;Chen LL;Meng X;Zhang C;Ip JD;Chan WM;Chu AW;Chan KH;Jin DY;Chen H;Yuen KY;To KK
新型SARS-CoV-2 Omicron变异株（B.1.1.529）于2021年11月初首次发现，引发了全球的广泛关注，它有超过50个突变，其中许多已知会影响传播性或导致免疫逃逸。在这项研究中，我们试图调查Omicron变体的病毒学特征，并将其与自2021年年中以来主导全球的Delta变体进行比较。在跨膜丝氨酸蛋白酶2（TMPRSS 2）过表达的VeroE 6（VeroE 6/TMPRSS 2）细胞中，Omicron变体的复制速度比Delta变体慢。值得注意的是，Delta变体在具有稳健TMPRSS 2表达的Calu 3细胞系中复制良好，而Omicron变体在该细胞系中复制较差。竞争试验表明Delta突变体在VeroE 6/TMPRSS 2和Calu 3细胞中的竞争能力优于Omicron突变体。为了证实Omicron和Delta变体之间进入途径的差异，我们评估了巴弗洛霉素A1、氯喹（抑制内吞途径）和卡莫司他（抑制TMPRSS 2途径）的抗病毒作用。卡莫司他有效抑制Delta变体，但不抑制Omicron变体，而巴弗洛霉素A1和氯喹可以抑制Omicron和Delta变体。此外，与Delta变体相比，Omicron变体在VeroE 6/TMPRSS 2细胞中也显示出较弱的细胞-细胞融合活性。总的来说，我们的研究结果表明，Omicron变体感染不是由TMPRSS 2增强的，而是主要通过内吞途径介导的。Omicron和Delta变体之间进入途径的差异可能对临床表现或疾病严重程度有影响。
The novel SARS-CoV-2 Omicron variant (B.1.1.529), first found in early November 2021, has sparked considerable global concern and it has >50 mutations, many of which are known to affect transmissibility or cause immune escape. In this study, we sought to investigate the virological characteristics of the Omicron variant and compared it with the Delta variant which has dominated the world since mid-2021. Omicron variant replicated more slowly than the Delta variant in transmembrane serine protease 2 (TMPRSS2)-overexpressing VeroE6 (VeroE6/TMPRSS2) cells. Notably, the Delta variant replicated well in Calu3 cell line which has robust TMPRSS2 expression, while the Omicron variant replicated poorly in this cell line. Competition assay showed that Delta variant outcompeted Omicron variant in VeroE6/TMPRSS2 and Calu3 cells. To confirm the difference in entry pathway between the Omicron and Delta variants, we assessed the antiviral effect of bafilomycin A1, chloroquine (inhibiting endocytic pathway), and camostat (inhibiting TMPRSS2 pathway). Camostat potently inhibited the Delta variant but not the Omicron variant, while bafilomycin A1 and chloroquine could inhibit both Omicron and Delta variants. Moreover, the Omicron variant also showed weaker cell–cell fusion activity when compared with Delta variant in VeroE6/TMPRSS2 cells. Collectively, our results suggest that Omicron variant infection is not enhanced by TMPRSS2 but is largely mediated via the endocytic pathway. The difference in entry pathway between Omicron and Delta variants may have an implication on the clinical manifestations or disease severity.
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影响因子：
64.5
作者：
Yeung ML;Teng JLL;Jia L;Zhang C;Huang C;Cai JP;Zhou R;Chan KH;Zhao H;Zhu L;Siu KL;Fung SY;Yung S;Chan TM;To KK;Chan JF;Cai Z;Lau SKP;Chen Z;Jin DY;Woo PCY;Yuen KY
通讯作者：
Yuen KY
影响因子：
11.1
作者：
Shuai H;Chan JF;Yuen TT;Yoon C;Hu JC;Wen L;Hu B;Yang D;Wang Y;Hou Y;Huang X;Chai Y;Chan CC;Poon VK;Lu L;Zhang RQ;Chan WM;Ip JD;Chu AW;Hu YF;Cai JP;Chan KH;Zhou J;Sridhar S;Zhang BZ;Yuan S;Zhang AJ;Huang JD;To KK;Yuen KY;Chu H
通讯作者：
Chu H
DOI：
10.1126/science.abl9463
发表时间：
2021-12-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
通讯作者：
--
影响因子：
168.9
作者：
Chan, Jasper Fuk-Woo;Yuan, Shuofeng;Yuen, Kwok-Yung
通讯作者：
Yuen, Kwok-Yung
影响因子：
64.8
作者：
Hoffmann, Markus;Moesbauer, Kirstin;Poehlmann, Stefan
通讯作者：
Poehlmann, Stefan