Identification and differential usage of a host metalloproteinase entry pathway by SARS-CoV-2 Delta and Omicron.

Autor:	Benlarbi M; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.; Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.; Centre for Infection, Immunity and Inflammation, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Laroche G; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.; Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.; Centre for Infection, Immunity and Inflammation, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Fink C; Department of Microbiology & Immunology, Schulich School of Medicine & Dentistry Western University, London, ON N6A 5C1, Canada.; Molecular Medicine Research Laboratories, Robarts Research Institute, University of Western Ontario, London, ON N6A 5C1, Canada., Fu K; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.; Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.; Centre for Infection, Immunity and Inflammation, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Mulloy RP; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.; Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.; Centre for Infection, Immunity and Inflammation, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Phan A; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.; Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.; Centre for Infection, Immunity and Inflammation, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Ariana A; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.; Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.; Centre for Infection, Immunity and Inflammation, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Stewart CM; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.; Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.; Centre for Infection, Immunity and Inflammation, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Prévost J; Centre de Recherche du CHUM, Montréal, QC H2X 0A9, Canada.; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC H3C 3J7, Canada., Beaudoin-Bussières G; Centre de Recherche du CHUM, Montréal, QC H2X 0A9, Canada.; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC H3C 3J7, Canada., Daniel R; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.; Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.; Centre for Infection, Immunity and Inflammation, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Bo Y; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.; Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.; Centre for Infection, Immunity and Inflammation, University of Ottawa, Ottawa, ON K1H 8M5, Canada., El Ferri O; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.; Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.; Centre for Infection, Immunity and Inflammation, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Yockell-Lelièvre J; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.; Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.; The Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Stanford WL; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.; Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.; The Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Giguère PM; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Mubareka S; Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada., Finzi A; Centre de Recherche du CHUM, Montréal, QC H2X 0A9, Canada.; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC H3C 3J7, Canada., Dekaban GA; Department of Microbiology & Immunology, Schulich School of Medicine & Dentistry Western University, London, ON N6A 5C1, Canada.; Molecular Medicine Research Laboratories, Robarts Research Institute, University of Western Ontario, London, ON N6A 5C1, Canada., Dikeakos JD; Department of Microbiology & Immunology, Schulich School of Medicine & Dentistry Western University, London, ON N6A 5C1, Canada.; Molecular Medicine Research Laboratories, Robarts Research Institute, University of Western Ontario, London, ON N6A 5C1, Canada., Côté M; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.; Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.; Centre for Infection, Immunity and Inflammation, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2022 Nov 18; Vol. 25 (11), pp. 105316. Date of Electronic Publication: 2022 Oct 10.
DOI:	10.1016/j.isci.2022.105316
Abstrakt:	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. Competing Interests: The authors declare that they have no conflict of interest. (© 2022 The Author(s).)
Databáze:	MEDLINE
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