Acquisition of the L452R Mutation in the ACE2-Binding Interface of Spike Protein Triggers Recent Massive Expansion of SARS-CoV-2 Variants.
Acquisition of the L452R Mutation in the ACE2-Binding Interface of Spike Protein Triggers Recent Massive Expansion of SARS-CoV-2 Variants.
复制标题
在刺突蛋白的ACE 2结合界面中获得L452 R突变触发了最近SARS-CoV-2变体的大规模扩增。
DOI：
10.1128/jcm.00921-21
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发表时间：
2021-10-19
影响因子：
9.4
通讯作者：
Sokurenko E
中科院分区：
文献类型：
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作者：
Tchesnokova V;Kulasekara H;Larson L;Bowers V;Rechkina E;Kisiela D;Sledneva Y;Choudhury D;Maslova I;Deng K;Kutumbaka K;Geng H;Fowler C;Greene D;Ralston J;Samadpour M;Sokurenko E
我们报道，最近有许多严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)的独立变异体在全球范围内扩张，这些变异体在Spike蛋白的受体结合域(RBD)上发生了突变L452R。L452R变异体的大量出现首先与血统B.1.427/B.1.429(分支21C)有关，该血统自2020年11月和12月以来一直在加利福尼亚州传播，最初命名为CAL.20C，目前是感兴趣的变异体epsilon。通过对临床标本中编码RBD的414到583个氨基酸的541个碱基片段的PCR扩增和Sanger测序，我们发现了一个独立的L452R变体，它也是最近在加利福尼亚州出现的，但来自谱系B.1.232，分支20A(命名为CAL.20A)。值得注意的是，2021年1月报道，CAL.20A导致圣地亚哥动物园的大猩猩感染。与在Spike蛋白的N末端区域携带两个额外突变的epsilon变体不同，L452R是在CAL.20A的Spike蛋白中发现的唯一突变。根据全基因组系统发育分析，这两种病毒变体的出现都是由获得L452R特异性地触发的，这表明对该突变有很强的阳性选择。全球分析显示，L452R几乎无所不在地存在于十几个独立出现的谱系中，包括最新的关注/兴趣变体Delta、kappa、epsilon和IOTA，其中lambda变体携带L452Q。L452位于RBD的血管紧张素转换酶2(ACE2)相互作用界面附近。据报道，L452R突变与免疫逃逸有关，并可能导致病毒更强的细胞附着，这两个因素都可能增加病毒的传播性、传染性和致病性。
We report that there is a recent global expansion of numerous independent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with mutation L452R in the receptor-binding domain (RBD) of the spike protein. The massive emergence of L452R variants was first linked to lineage B.1.427/B.1.429 (clade 21C) that has been spreading in California since November and December 2020, originally named CAL.20C and currently variant of interest epsilon. By PCR amplification and Sanger sequencing of a 541-base fragment coding for amino acids 414 to 583 of the RBD from a collection of clinical specimens, we identified a separate L452R variant that also recently emerged in California but derives from the lineage B.1.232, clade 20A (named CAL.20A). Notably, CAL.20A caused an infection in gorillas in the San Diego Zoo, reported in January 2021. Unlike the epsilon variant that carries two additional mutations in the N-terminal domain of spike protein, L452R is the only mutation found in the spike proteins of CAL.20A. Based on genome-wide phylogenetic analysis, emergence of both viral variants was specifically triggered by acquisition of L452R, suggesting a strong positive selection for this mutation. Global analysis revealed that L452R is nearly omnipresent in a dozen independently emerged lineages, including the most recent variants of concern/interest delta, kappa, epsilon and iota, with the lambda variant carrying L452Q. L452 is in immediate proximity to the angiotensin-converting enzyme 2 (ACE2) interaction interface of RBD. It was reported that the L452R mutation is associated with immune escape and could result in a stronger cell attachment of the virus, with both factors likely increasing viral transmissibility, infectivity, and pathogenicity.