Omicron: increased transmissibility and decreased pathogenicity.
Omicron: increased transmissibility and decreased pathogenicity.
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DOI：
10.1038/s41392-022-01009-8
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发表时间：
2022-05-07
影响因子：
39.3
通讯作者：
Szechenyi, Aleksandar
中科院分区：
文献类型：
--
作者：
Balint, Gabor;Voros-Horvath, Barbara;Szechenyi, Aleksandar
最近发表了三篇研究论文，比较了Omicron变种与早期变种(VOC)的病毒学特性。1-3 SARS-CoV-2 B.529变种奥米克龙于2021年10月在南非首次发现，并迅速传播；三个月内，它出现在87多个国家。4在对早期新冠肺炎变异株和奥美康的流行病学资料和突变监测中，主要表现在复制率和住院时间上有显著差异。虽然在Omicron的病例中可以观察到适度的严重性，但它的传播率2(图1d)比Delta变体高3.31倍，并且对抗病毒免疫1的抵抗力增加代表着全球流行威胁。与早期的SARS-CoV-2变异体相比，它的Spike蛋白具有更多的突变，其中S2区域的6个突变是独一无二的。Furin裂解位点区域的三个突变(P681H、H655Y、N679K)减少了与发病相关的S1/S2裂解、融合和合胞体形成。多个氨基酸取代可能导致Omicron的S蛋白(包括Q493R、Q489R和S477N)中ACE2结合亲和力增加(图1a)。这些突变通过形成ACE2盐桥和ACE2氢键导致ACE2结合增强。2用冷冻电子显微镜和X射线结晶学等先进的结构测定方法进行分析，证实了这些结果，并与新的突变和新的化学作用位点直接相关。5用生物层析干涉法测定ACE2的亲和力。Omicron RBD与ACE2的结合亲和力是武汉-HU-1和Delta的3倍。1用ACE2抗体滴定全长尖峰的细胞，证实了这一发现。1受体亲和力和受体在细胞中的表达影响病毒的趋向性，对此进行了详细的研究。体外人体组织标本的免疫组织化学染色显示，ACE2在支气管中的表达高于在肺中的表达，而对TMPRSS2的mRNA表达水平分析表明，TMPRSS2的分布相似。3人肺组织的单核RNA测序显示，TMPRSS2在气管中的表达低于肺泡。1血管紧张素转换酶2的表达低于TMPRSS2，但在特定的细胞类型，如AT1、AT2和俱乐部细胞中略有升高。1定量聚合酶链式反应显示肺组织中TMPRSS2mRNA的表达高于上呼吸道支气管组织。1在多细胞培养的复制研究中，TMPRSS2的高表达有利于Delta变异体的生长，这与Omicron Spike蛋白的切割受损有关。3.
Three research papers were published recently to compare the virological properties of the Omicron variant with the earlier variants of concern (VOC). 1-3 The SARS-CoV-2 B. 1.1. 529 variant, Omicron, was first detected in South Africa in October 2021 and has spread rapidly; within three months, it appeared in more than 87 countries. 4 During the surveillance of the epidemiological data and mutations of earlier COVID-19 variants and Omicron, significant differences were revealed mainly in the reproduction rate and hospitalization. Although a modest severity can be observed in the case of Omicron, its 3, 31-fold higher transmissibility 2 (Fig. 1 d) than Delta variant and increased resistance to antiviral immunity 1 represents a global epidemic threat. Comparing the earlier SARS-CoV-2 variants with Omicron, it bears more mutations in its Spike protein, of which six in the S2 region are unique. Three mutations in the furin cleavage site region (P681H, H655Y, N679K) decrease S1/S2 cleavage, fusogenicity, and syncytia formation associated with pathogenesis. The multiple amino acid substitutions presumably cause the increased ACE2 binding affinity of Omicron in its S-protein, including Q493R, Q489R, and S477N (Fig. 1 a). These mutations cause enhancement of ACE2 binding via the formation of ACE2 salt bridge and ACE2 H-bond. 2 Analysis using advanced structure determining methods such as cryo-electron microscopy and X-ray crystallography confirmed these results and directly connected novel mutations and new chemical interaction sites. 5 The ACE2 affinity was determined experimentally, using biolayer interferometry. Omicron RBD displayed a threefold higher binding affinity for ACE2 compared to Wuhan-HU-1 and Delta. 1 This finding was confirmed by ACE2 antibody titration on cells transfected with a full-length spike. 1 The receptor affinity and the receptor expression in cells affect viral tropism, which was examined in detail.Immunohistochemical staining of ex vivo human tissue samples indicated higher ACE2 expression in bronchus than in lung, while analysis of mRNA expression levels indicated a similar distribution of TMPRSS2. 3 Single-nuclei RNA sequencing performed on human lung tissues showed lower expression of TMPRSS2 in the trachea compared to alveoli. 1 ACE2 expression was lower than TMPRSS2, although slightly elevated in specific cell types, such as AT1, AT2, and club cells. 1 qPCR showed higher TMPRSS2 mRNA expression in lung parenchyma compared to upper airway bronchial tissue samples. 1 In replication studies using multiple cell cultures, higher TMPRSS2 expression was revealed to favor the growth of delta variant, which relates to the impaired cleavage of the Omicron spike protein. 3
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影响因子：
56.9
作者：
McCallum, Matthew;Czudnochowski, Nadine;Rosen, Laura E.;Zepeda, Samantha K.;Bowen, John E.;Walls, Alexandra C.;Hauser, Kevin;Joshi, Anshu;Stewart, Cameron;Dillen, Josh R.;Powell, Abigail E.;Croll, Tristan, I;Nix, Jay;Virgin, Herbert W.;Corti, Davide;Snell, Gyorgy;Veesler, David
通讯作者：
Veesler, David
影响因子：
64.8
作者：
Meng B;Abdullahi A;Ferreira IATM;Goonawardane N;Saito A;Kimura I;Yamasoba D;Gerber PP;Fatihi S;Rathore S;Zepeda SK;Papa G;Kemp SA;Ikeda T;Toyoda M;Tan TS;Kuramochi J;Mitsunaga S;Ueno T;Shirakawa K;Takaori-Kondo A;Brevini T;Mallery DL;Charles OJ;CITIID-NIHR BioResource COVID-19 Collaboration;Genotype to Phenotype Japan (G2P-Japan) Consortium;Ecuador-COVID19 Consortium;Bowen JE;Joshi A;Walls AC;Jackson L;Martin D;Smith KGC;Bradley J;Briggs JAG;Choi J;Madissoon E;Meyer KB;Mlcochova P;Ceron-Gutierrez L;Doffinger R;Teichmann SA;Fisher AJ;Pizzuto MS;de Marco A;Corti D;Hosmillo M;Lee JH;James LC;Thukral L;Veesler D;Sigal A;Sampaziotis F;Goodfellow IG;Matheson NJ;Sato K;Gupta RK
通讯作者：
Gupta RK
影响因子：
64.8
作者：
Viana R;Moyo S;Amoako DG;Tegally H;Scheepers C;Althaus CL;Anyaneji UJ;Bester PA;Boni MF;Chand M;Choga WT;Colquhoun R;Davids M;Deforche K;Doolabh D;du Plessis L;Engelbrecht S;Everatt J;Giandhari J;Giovanetti M;Hardie D;Hill V;Hsiao NY;Iranzadeh A;Ismail A;Joseph C;Joseph R;Koopile L;Kosakovsky Pond SL;Kraemer MUG;Kuate-Lere L;Laguda-Akingba O;Lesetedi-Mafoko O;Lessells RJ;Lockman S;Lucaci AG;Maharaj A;Mahlangu B;Maponga T;Mahlakwane K;Makatini Z;Marais G;Maruapula D;Masupu K;Matshaba M;Mayaphi S;Mbhele N;Mbulawa MB;Mendes A;Mlisana K;Mnguni A;Mohale T;Moir M;Moruisi K;Mosepele M;Motsatsi G;Motswaledi MS;Mphoyakgosi T;Msomi N;Mwangi PN;Naidoo Y;Ntuli N;Nyaga M;Olubayo L;Pillay S;Radibe B;Ramphal Y;Ramphal U;San JE;Scott L;Shapiro R;Singh L;Smith-Lawrence P;Stevens W;Strydom A;Subramoney K;Tebeila N;Tshiabuila D;Tsui J;van Wyk S;Weaver S;Wibmer CK;Wilkinson E;Wolter N;Zarebski AE;Zuze B;Goedhals D;Preiser W;Treurnicht F;Venter M;Williamson C;Pybus OG;Bhiman J;Glass A;Martin DP;Rambaut A;Gaseitsiwe S;von Gottberg A;de Oliveira T
通讯作者：
de Oliveira T
影响因子：
64.8
作者：
Suzuki R;Yamasoba D;Kimura I;Wang L;Kishimoto M;Ito J;Morioka Y;Nao N;Nasser H;Uriu K;Kosugi Y;Tsuda M;Orba Y;Sasaki M;Shimizu R;Kawabata R;Yoshimatsu K;Asakura H;Nagashima M;Sadamasu K;Yoshimura K;Genotype to Phenotype Japan (G2P-Japan) Consortium;Sawa H;Ikeda T;Irie T;Matsuno K;Tanaka S;Fukuhara T;Sato K
通讯作者：
Sato K
影响因子：
64.8
作者：
Hui, Kenrie P. Y.;Ho, John C. W.;Chan, Michael C. W.
通讯作者：
Chan, Michael C. W.