Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...

Details

Autor(en) / Beteiligte
Titel
Loss of furin cleavage site attenuates SARS-CoV-2 pathogenesis
Ist Teil von
  • Nature (London), 2021-03, Vol.591 (7849), p.293-299
Ort / Verlag
England: Nature Publishing Group
Erscheinungsjahr
2021
Link zum Volltext
Beschreibungen/Notizen
  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-a new coronavirus that has led to a worldwide pandemic -has a furin cleavage site (PRRAR) in its spike protein that is absent in other group-2B coronaviruses . 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 (ΔPRRA). Here we report that replicates of ΔPRRA 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 ΔPRRA 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 ΔPRRA 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 ΔPRRA 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.
Sprache
Englisch
Identifikatoren
ISSN: 0028-0836, 1476-4687
eISSN: 1476-4687
DOI: 10.1038/s41586-021-03237-4
Titel-ID: cdi_pubmed_primary_33494095

Weiterführende Literatur

Empfehlungen zum selben Thema automatisch vorgeschlagen von bX