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Biological Sciences - Article
Recurrent independent emergence and transmission of SARS-CoV-2 Spike amino acid H69/V70 deletions
Ravindra Gupta
University of Cambridge
Corresponding Author
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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.
Keywords
SARS-CoV-2, COVID-19, antibody escape, neutralising antibodies, mutation, evasion, resistance, fitness, evolution
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Steven Mann
commented on 11 January, 2021
A very interesting read, I dont suppose you will be performing a more in depth analysis of resistance to vaccine? I read the article in which you monitored the effects of CP treatment on a strain containing the 69/70 deletion. Would be interested to know what the general effects on the vaccine could be.
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This is a preprint. It has not completed peer review.
Biological Sciences - Article
Recurrent independent emergence and transmission of SARS-CoV-2 Spike amino acid H69/V70 deletions
Ravindra Gupta
University of Cambridge
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Under Review
Version 1
Posted 04 Jan, 2021
Metrics
Comments: 1
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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.
Figure 1
Figure 2
Figure 3
Figure 4
Steven Mann
commented on 11 January, 2021
A very interesting read, I dont suppose you will be performing a more in depth analysis of resistance to vaccine? I read the article in which you monitored the effects of CP treatment on a strain containing the 69/70 deletion. Would be interested to know what the general effects on the vaccine could be.