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


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Authors
Albecka, Anna 
Cattin-Ortolá, Jérôme  ORCID logo  https://orcid.org/0000-0002-8988-4265
Abstract

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.

Description
Keywords
Research Article, Biology and life sciences, Medicine and health sciences, Research and analysis methods
Journal Title
PLOS Pathogens
Conference Name
Journal ISSN
1553-7366
1553-7374
Volume Title
17
Publisher
Public Library of Science