| Autor: |
Mehdi Benlarbi, Geneviève Laroche, Corby Fink, Kathy Fu, Rory P. Mulloy, Alexandra Phan, Ardeshir Ariana, Corina M. Stewart, Jérémie Prévost, Guillaume Beaudoin-Bussières, Redaet Daniel, Yuxia Bo, Omar El Ferri, Julien Yockell-Lelièvre, William L. Stanford, Patrick M. Giguère, Samira Mubareka, Andrés Finzi, Gregory A. Dekaban, Jimmy D. Dikeakos, Marceline Côté |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
iScience, Vol 25, Iss 11, Pp 105316- (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2589-0042 |
| DOI: |
10.1016/j.isci.2022.105316 |
| Popis: |
Summary: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike glycoprotein (S) binds to angiotensin-converting enzyme 2 (ACE2) to mediate membrane fusion via two distinct pathways: 1) a surface, serine protease-dependent or 2) an endosomal, cysteine protease-dependent pathway. In this study, we found that SARS-CoV-2 S has a wider protease usage and can also be activated by TMPRSS13 and matrix metalloproteinases (MMPs). We found that MMP-2 and MMP-9 played roles in SARS-CoV-2 S cell-cell fusion and TMPRSS2- and cathepsin-independent viral entry in cells expressing high MMP levels. MMP-dependent viral entry required cleavage at the S1/S2 junction in viral producer cells, and differential processing of variants of concern S dictated its usage; the efficiently processed Delta S preferred metalloproteinase-dependent entry when available, and less processed Omicron S was unable to us metalloproteinases for entry. As MMP-2/9 are released during inflammation, they may play roles in S-mediated cytopathic effects, tropism, and disease outcome. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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