Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape

• Published in: Science (American Association for the Advancement of Science) Vol. 371; no. 6534; pp. 1139 - 1142
• Main Authors: McCarthy, Kevin R., Rennick, Linda J., Nambulli, Sham, Robinson-McCarthy, Lindsey R., Bain, William G., Haidar, Ghady, Duprex, W. Paul
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 12.03.2021; American Association for the Advancement of Science
• Subjects: Amino Acid Sequence; Amino Acid Substitution; Amino acids; Antibodies; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; Antigenicity; Antigens; Antigens, Viral - chemistry; Antigens, Viral - genetics; Coronaviridae; Coronaviruses; COVID-19; COVID-19 - virology; Deletion; Disease transmission; DNA-directed RNA polymerase; Editing; Epitopes; Evolution; Evolution & development; Evolution, Molecular; Genetic diversity; Genetic Drift; Glycoproteins; Human populations; Humans; Immune Evasion; Influenza; Pandemics; Proofreading; Protein Conformation; Recurrent infection; Respiratory diseases; Ribonucleic acid; RNA; RNA polymerase; RNA viruses; RNA-directed RNA polymerase; SARS-CoV-2 - genetics; Sequence Deletion; Severe acute respiratory syndrome coronavirus 2; Spike glycoprotein; Spike Glycoprotein, Coronavirus - chemistry; Spike Glycoprotein, Coronavirus - genetics; Spike protein; Viral diseases; Virology; Viruses
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.abf6950

Influenza viruses evade immunity initiated by previous infection, which explains recurrent influenza pandemics. Unlike the error-prone RNA-dependent RNA polymerase of influenza, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and related viruses contain polymerases with proofreading activity. However, proofreading cannot correct deletions, which during a long-term persistent infection could result in the generation of viruses showing alteration of entire stretches of amino acids and the structures they form. McCarthy et al. identified an evolutionary signature defined by prevalent and recurrent deletions in the spike protein of SARS-CoV-2 at four antigenic sites. Deletion variants show human-to-human transmission of viruses with altered antigenicity. Science , this issue p. 1139 SARS-CoV-2 genome deletions that arise independently in persistently infected individuals show recurrent and convergent evolution. Zoonotic pandemics, such as that caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can follow the spillover of animal viruses into highly susceptible human populations. The descendants of these viruses have adapted to the human host and evolved to evade immune pressure. Coronaviruses acquire substitutions more slowly than other RNA viruses. In the spike glycoprotein, we found that recurrent deletions overcome this slow substitution rate. Deletion variants arise in diverse genetic and geographic backgrounds, transmit efficiently, and are present in novel lineages, including those of current global concern. They frequently occupy recurrent deletion regions (RDRs), which map to defined antibody epitopes. Deletions in RDRs confer resistance to neutralizing antibodies. By altering stretches of amino acids, deletions appear to accelerate SARS-CoV-2 antigenic evolution and may, more generally, drive adaptive evolution.