Details

Autor(en) / Beteiligte

• Papa, Guido
• Mallery, Donna L
• Albecka, Anna
• Welch, Lawrence G
• Cattin-Ortolá, Jérôme
• Luptak, Jakub
• Paul, David
• McMahon, Harvey T
• Goodfellow, Ian G
• Carter, Andrew
• Munro, Sean
• James, Leo C
• Lee, Benhur

Titel

Furin cleavage of SARS-CoV-2 Spike promotes but is not essential for infection and cell-cell fusion

Ist Teil von

• PLoS pathogens, 2021-01, Vol.17 (1), p.e1009246-e1009246

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infects cells by binding to the host cell receptor ACE2 and undergoing virus-host membrane fusion. Fusion is triggered by the protease TMPRSS2, which processes the viral Spike (S) protein to reveal the fusion peptide. SARS-CoV-2 has evolved a multibasic site at the S1-S2 boundary, which is thought to be cleaved by furin in order to prime S protein for TMPRSS2 processing. Here we show that CRISPR-Cas9 knockout of furin reduces, but does not prevent, the production of infectious SARS-CoV-2 virus. Comparing S processing in furin knockout cells to multibasic site mutants reveals that while loss of furin substantially reduces S1-S2 cleavage it does not prevent it. SARS-CoV-2 S protein also mediates cell-cell fusion, potentially allowing virus to spread virion-independently. We show that loss of furin in either donor or acceptor cells reduces, but does not prevent, TMPRSS2-dependent cell-cell fusion, unlike mutation of the multibasic site that completely prevents syncytia formation. Our results show that while furin promotes both SARS-CoV-2 infectivity and cell-cell spread it is not essential, suggesting furin inhibitors may reduce but not abolish viral spread.