TY - JOUR
T1 - Expanding repertoire of SARS-CoV-2 deletion mutations contributes to evolution of highly transmissible variants
AU - Venkatakrishnan, A. J.
AU - Anand, Praveen
AU - Lenehan, Patrick J.
AU - Ghosh, Pritha
AU - Suratekar, Rohit
AU - Silvert, Eli
AU - Pawlowski, Colin
AU - Siroha, Abhishek
AU - Chowdhury, Dibyendu Roy
AU - O’Horo, John C.
AU - Yao, Joseph D.
AU - Pritt, Bobbi S.
AU - Norgan, Andrew P.
AU - Hurt, Ryan T.
AU - Badley, Andrew D.
AU - Halamka, John
AU - Soundararajan, Venky
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - The emergence of highly transmissible SARS-CoV-2 variants and vaccine breakthrough infections globally mandated the characterization of the immuno-evasive features of SARS-CoV-2. Here, we systematically analyzed 2.13 million SARS-CoV-2 genomes from 188 countries/territories (up to June 2021) and performed whole-genome viral sequencing from 102 COVID-19 patients, including 43 vaccine breakthrough infections. We identified 92 Spike protein mutations that increased in prevalence during at least one surge in SARS-CoV-2 test positivity in any country over a 3-month window. Deletions in the Spike protein N-terminal domain were highly enriched for these ‘surge-associated mutations’ (Odds Ratio = 14.19, 95% CI 6.15–32.75, p value = 3.41 × 10–10). Based on a longitudinal analysis of mutational prevalence globally, we found an expanding repertoire of Spike protein deletions proximal to an antigenic supersite in the N-terminal domain that may be one of the key contributors to the evolution of highly transmissible variants. Finally, we generated clinically annotated SARS-CoV-2 whole genome sequences from 102 patients and identified 107 unique mutations, including 78 substitutions and 29 deletions. In five patients, we identified distinct deletions between residues 85–90, which reside within a linear B cell epitope. Deletions in this region arose contemporaneously on a diverse background of variants across the globe since December 2020. Overall, our findings based on genomic-epidemiology and clinical surveillance suggest that the genomic deletion of dispensable antigenic regions in SARS-CoV-2 may contribute to the evasion of immune responses and the evolution of highly transmissible variants.
AB - The emergence of highly transmissible SARS-CoV-2 variants and vaccine breakthrough infections globally mandated the characterization of the immuno-evasive features of SARS-CoV-2. Here, we systematically analyzed 2.13 million SARS-CoV-2 genomes from 188 countries/territories (up to June 2021) and performed whole-genome viral sequencing from 102 COVID-19 patients, including 43 vaccine breakthrough infections. We identified 92 Spike protein mutations that increased in prevalence during at least one surge in SARS-CoV-2 test positivity in any country over a 3-month window. Deletions in the Spike protein N-terminal domain were highly enriched for these ‘surge-associated mutations’ (Odds Ratio = 14.19, 95% CI 6.15–32.75, p value = 3.41 × 10–10). Based on a longitudinal analysis of mutational prevalence globally, we found an expanding repertoire of Spike protein deletions proximal to an antigenic supersite in the N-terminal domain that may be one of the key contributors to the evolution of highly transmissible variants. Finally, we generated clinically annotated SARS-CoV-2 whole genome sequences from 102 patients and identified 107 unique mutations, including 78 substitutions and 29 deletions. In five patients, we identified distinct deletions between residues 85–90, which reside within a linear B cell epitope. Deletions in this region arose contemporaneously on a diverse background of variants across the globe since December 2020. Overall, our findings based on genomic-epidemiology and clinical surveillance suggest that the genomic deletion of dispensable antigenic regions in SARS-CoV-2 may contribute to the evasion of immune responses and the evolution of highly transmissible variants.
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U2 - 10.1038/s41598-022-26646-5
DO - 10.1038/s41598-022-26646-5
M3 - Article
AN - SCOPUS:85145720676
SN - 2045-2322
VL - 13
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 257
ER -