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《Nature，1月25日，Loss of furin cleavage site attenuates SARS-CoV-2 pathogenesis》

  • 来源专题：COVID-19科研动态监测
  • 编译者： zhangmin
  • 发布时间：2021-02-22

  • Loss of furin cleavage site attenuates SARS-CoV-2 pathogenesis

    Bryan A. Johnson, Xuping Xie, […]Vineet D. Menachery

    Nature (2021)

    Abstract

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—a new coronavirus that has led to a worldwide pandemic1—has a furin cleavage site (PRRAR) in its spike protein that is absent in other group-2B coronaviruses2. 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.

  • 原文来源：https://www.nature.com/articles/s41586-021-03237-4
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