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Mutations in SARS-CoV-2 variants of concern link to increased spike cleavage and virus transmission.

Cell host & microbe | 2022

SARS-CoV-2 lineages have diverged into highly prevalent variants termed "variants of concern" (VOCs). Here, we characterized emerging SARS-CoV-2 spike polymorphisms in vitro and in vivo to understand their impact on transmissibility and virus pathogenicity and fitness. We demonstrate that the substitution S:655Y, represented in the gamma and omicron VOCs, enhances viral replication and spike protein cleavage. The S:655Y substitution was transmitted more efficiently than its ancestor S:655H in the hamster infection model and was able to outcompete S:655H in the hamster model and in a human primary airway system. Finally, we analyzed a set of emerging SARS-CoV-2 variants to investigate how different sets of mutations may impact spike processing. All VOCs tested exhibited increased spike cleavage and fusogenic capacity. Taken together, our study demonstrates that the spike mutations present in VOCs that become epidemiologically prevalent in humans are linked to an increase in spike processing and virus transmission.

Pubmed ID: 35150638 RIS Download

Associated grants

  • Agency: NCI NIH HHS, United States
    Id: U54 CA260560
  • Agency: NIAID NIH HHS, United States
    Id: U19 AI142733
  • Agency: NIAID NIH HHS, United States
    Id: U19 AI135990
  • Agency: NIH HHS, United States
    Id: S10 OD026880
  • Agency: NIH HHS, United States
    Id: S10 OD030463
  • Agency: NIGMS NIH HHS, United States
    Id: P20 GM130448
  • Agency: NIAID NIH HHS, United States
    Id: HHSN272201400006C
  • Agency: NIAID NIH HHS, United States
    Id: U19 AI135972
  • Agency: NIAID NIH HHS, United States
    Id: 75N93021C00014

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