Recurrent independent emergence and transmission of SARS-CoV-2 Spike amino acid H69/V70 deletions
Recurrent independent emergence and transmission of SARS-CoV-2 Spike amino acid H69/V70 deletions
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DOI：
10.21203/rs.3.rs-136937/v1
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发表时间：
2021-01
期刊：
影响因子：
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通讯作者：
Ravindra K. Gupta;S. Kemp;William T. Harvey;Spyros Lytras;A. Carabelli;D. Robertson
中科院分区：
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作者：
Ravindra K. Gupta;S. Kemp;William T. Harvey;Spyros Lytras;A. Carabelli;D. Robertson
SARS-CoV-2受体结合结构域（RBD）中刺突氨基酸的替换相对频繁地发生，并且一些具有免疫识别的后果。在这里，我们报告经常出现和显着向前传输的S基因中的六个核苷酸的缺失，这导致两个氨基酸的损失：H69和V70。特别值得注意的是，这种缺失，即N4H69/V70，通常与受体结合基序氨基酸置换N501 Y、N439 K和Y 453 F共同发生。B.1.1.7是SARS-CoV-2的一个谱系，由来自英国的4000多个SARS-CoV-2基因组序列组成，包括其他8个S基因突变：RBD（N501 Y和A570 D），S1（B.1.1.7）和S2（P681 H，T716 I，S982 A和D1118 H）。𝚫𝚫𝚫其中一些突变可能是由于病毒在感染个体中的免疫选择压力下进化而产生的，至少有一个，谱系B.1.1.7，可能来自慢性感染。鉴于我们最近的证据表明，DH 69/V70增强了病毒感染性（肯普et al. 2020），其对病毒适应度的影响似乎与RBD变化无关。应优先考虑加强对有和无RBD突变的H69/V70缺失的监测。允许的突变，如SARH69/V70，有可能增强SARS-CoV-2产生新变体的能力，包括疫苗逃逸变体，否则会显着降低病毒适应性。
SARS-CoV-2 Spike amino acid replacements in the receptor binding domain (RBD) occur relatively frequently and some have a consequence for immune recognition. Here we report recurrent emergence and significant onward transmission of a six-nucleotide deletion in the S gene, which results in loss of two amino acids: H69 and V70. Of particular note this deletion, 𝚫H69/V70, often co-occurs with the receptor binding motif amino acid replacements N501Y, N439K and Y453F. One of the 𝚫H69/V70+ N501Y lineages, B.1.1.7, is comprised of over 4000 SARS-CoV-2 genome sequences from the UK and includes eight other S gene mutations: RBD (N501Y and A570D), S1 (𝚫H69/V70 and 𝚫144/145) and S2 (P681H, T716I, S982A and D1118H). Some of these mutations have presumably arisen as a result of the virus evolving from immune selection pressure in infected individuals and at least one, lineage B.1.1.7, potentially from a chronic infection. Given our recent evidence that 𝚫H69/V70 enhances viral infectivity (Kemp et al. 2020), its effect on virus fitness appears to be independent to the RBD changes. Enhanced surveillance for the 𝚫H69/V70 deletion with and without RBD mutations should be considered as a priority. Permissive mutations such as 𝚫H69/V70 have the potential to enhance the ability of SARS-CoV-2 to generate new variants, including vaccine escape variants, that would have otherwise significantly reduced viral fitness.