Antibody escape and cryptic cross-domain stabilization in the SARS-CoV-2 Omicron spike protein.
Antibody escape and cryptic cross-domain stabilization in the SARS-CoV-2 Omicron spike protein.
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DOI：
10.1016/j.chom.2022.07.016
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发表时间：
2022-09-14
影响因子：
30.3
通讯作者：
Gollihar, Jimmy D.
中科院分区：
文献类型：
--
作者：
Javanmardi, Kamyab;Segall-Shapiro, Thomas H.;Chou, Chia-Wei;Boutz, Daniel R.;Olsen, Randall J.;Xie, Xuping;Xia, Hongjie;Shi, Pei-Yong;Johnson, Charlie D.;Annapareddy, Ankur;Weaver, Scott;Musser, James M.;Ellington, Andrew D.;Finkelstein, Ilya J.;Gollihar, Jimmy D.
严重急性呼吸系统综合征冠状病毒2（SARS-CoV-2）在全球范围内的传播导致了令人担忧的变异体的反复出现。对于Omicron变体，亚谱系BA.1和BA.2分别含有33和29个非同义和插入缺失刺突蛋白突变。这些氨基酸取代和插入缺失涉及增加的可传递性和增强的免疫逃避。通过回复BA.1或BA.2的单个刺突突变，我们表征了Omicron刺突突变对表达、ACE 2受体亲和力和中和抗体识别的分子效应。我们确定了能够在多种表位处逃避中和抗体的关键突变。刺突蛋白的N-末端和S2结构域中的稳定突变可以补偿受体结合结构域中的不稳定突变，从而使Omicron中的突变数量达到创纪录水平。我们的研究结果提供了一个全面的说明突变的影响，在Omicron刺突蛋白，并说明以前未知的主机逃避机制。Omicron BA.1和BA.2变体具有前所未有数量的非同义和插入缺失刺突蛋白突变。Javanmarti等人报告了在不同蛋白质背景下，由于这些突变引起的抗原性、表达和hACE 2亲和力变化。这项研究揭示了隐藏的跨域相互作用，增强抗体逃逸和稳定的刺突蛋白。
The worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the repeated emergence of variants of concern. For the Omicron variant, sub-lineages BA.1 and BA.2, respectively, contain 33 and 29 nonsynonymous and indel spike protein mutations. These amino acid substitutions and indels are implicated in increased transmissibility and enhanced immune evasion. By reverting individual spike mutations of BA.1 or BA.2, we characterize the molecular effects of the Omicron spike mutations on expression, ACE2 receptor affinity, and neutralizing antibody recognition. We identified key mutations enabling escape from neutralizing antibodies at a variety of epitopes. Stabilizing mutations in the N-terminal and S2 domains of the spike protein can compensate for destabilizing mutations in the receptor binding domain, enabling the record number of mutations in Omicron. Our results provide a comprehensive account of the mutational effects in the Omicron spike protein and illustrate previously uncharacterized mechanisms of host evasion. The Omicron BA.1 and BA.2 variants have unprecedented numbers of nonsynonymous and indel spike protein mutations. Javanmardi et al. report the antigenicity, expression, and hACE2 affinity changes due to these mutations, in different protein contexts. This study reveals cryptic cross-domain interactions that enhance antibody escape and stabilize the spike protein.
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影响因子：
16.6
作者：
Greaney AJ;Starr TN;Barnes CO;Weisblum Y;Schmidt F;Caskey M;Gaebler C;Cho A;Agudelo M;Finkin S;Wang Z;Poston D;Muecksch F;Hatziioannou T;Bieniasz PD;Robbiani DF;Nussenzweig MC;Bjorkman PJ;Bloom JD
通讯作者：
Bloom JD
影响因子：
8.8
作者：
Cerutti G;Guo Y;Liu L;Liu L;Zhang Z;Luo Y;Huang Y;Wang HH;Ho DD;Sheng Z;Shapiro L
通讯作者：
Shapiro L
影响因子：
16
作者：
Javanmardi K;Chou CW;Terrace CI;Annapareddy A;Kaoud TS;Guo Q;Lutgens J;Zorkic H;Horton AP;Gardner EC;Nguyen G;Boutz DR;Goike J;Voss WN;Kuo HC;Dalby KN;Gollihar JD;Finkelstein IJ
通讯作者：
Finkelstein IJ
影响因子：
64.8
作者：
Barnes CO;Jette CA;Abernathy ME;Dam KA;Esswein SR;Gristick HB;Malyutin AG;Sharaf NG;Huey-Tubman KE;Lee YE;Robbiani DF;Nussenzweig MC;West AP Jr;Bjorkman PJ
通讯作者：
Bjorkman PJ
SARS-COV-2血统的估计可传播和影响B.1.1.7在英国。
DOI：
10.1126/science.abg3055
发表时间：
2021-04-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Davies NG;Abbott S;Barnard RC;Jarvis CI;Kucharski AJ;Munday JD;Pearson CAB;Russell TW;Tully DC;Washburne AD;Wenseleers T;Gimma A;Waites W;Wong KLM;van Zandvoort K;Silverman JD;CMMID COVID-19 Working Group;COVID-19 Genomics UK (COG-UK) Consortium;Diaz-Ordaz K;Keogh R;Eggo RM;Funk S;Jit M;Atkins KE;Edmunds WJ
通讯作者：
Edmunds WJ