| First Author | Johnson BA | Year | 2021 |
| Journal | Nature | Volume | 591 |
| Issue | 7849 | Pages | 293-299 |
| PubMed ID | 33494095 | Mgi Jnum | J:307033 |
| Mgi Id | MGI:6710173 | Doi | 10.1038/s41586-021-03237-4 |
| Citation | Johnson BA, et al. (2021) Loss of furin cleavage site attenuates SARS-CoV-2 pathogenesis. Nature 591(7849):293-299 |
| abstractText | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-a new coronavirus that has led to a worldwide pandemic(1)-has a furin cleavage site (PRRAR) in its spike protein that is absent in other group-2B coronaviruses(2). To explore whether the furin cleavage site contributes to infection and pathogenesis in this virus, we generated a mutant SARS-CoV-2 that lacks the furin cleavage site (DeltaPRRA). Here we report that replicates of DeltaPRRA SARS-CoV-2 had faster kinetics, improved fitness in Vero E6 cells and reduced spike protein processing, as compared to parental SARS-CoV-2. However, the DeltaPRRA mutant had reduced replication in a human respiratory cell line and was attenuated in both hamster and K18-hACE2 transgenic mouse models of SARS-CoV-2 pathogenesis. Despite reduced disease, the DeltaPRRA mutant conferred protection against rechallenge with the parental SARS-CoV-2. Importantly, the neutralization values of sera from patients with coronavirus disease 2019 (COVID-19) and monoclonal antibodies against the receptor-binding domain of SARS-CoV-2 were lower against the DeltaPRRA mutant than against parental SARS-CoV-2, probably owing to an increased ratio of particles to plaque-forming units in infections with the former. Together, our results demonstrate a critical role for the furin cleavage site in infection with SARS-CoV-2 and highlight the importance of this site for evaluating the neutralization activities of antibodies. |
