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A SARS-CoV-2 – host proximity interactome

Payman Samavarchi-Tehrani, Hala Abdouni, James D.R. Knight, Audrey Astori, Reuben Samson, Zhen-Yuan Lin, Dae-Kyum Kim, Jennifer J. Knapp, Jonathan St-Germain, Christopher D. Go, Brett Larsen, Cassandra J. Wong, Patricia Cassonnet, Caroline Demeret, Yves Jacob, View ORCID ProfileFrederick P. Roth, Brian Raught, View ORCID ProfileAnne-Claude Gingras
doi: https://doi.org/10.1101/2020.09.03.282103
Payman Samavarchi-Tehrani
1Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
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Hala Abdouni
1Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
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James D.R. Knight
1Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
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Audrey Astori
2Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
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Reuben Samson
1Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
3Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada
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Zhen-Yuan Lin
1Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
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Dae-Kyum Kim
1Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
4Donnelly Centre, University of Toronto, Toronto, Ontario, Canada
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Jennifer J. Knapp
1Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
4Donnelly Centre, University of Toronto, Toronto, Ontario, Canada
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Jonathan St-Germain
2Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
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Christopher D. Go
1Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
3Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada
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Brett Larsen
1Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
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Cassandra J. Wong
1Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
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Patricia Cassonnet
5Département de Virologie, Unité de Génétique Moléculaire des Virus à ARN (GMVR), Institut Pasteur, UMR3569, Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot, Sorbonne Paris Cité, Paris, France
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Caroline Demeret
5Département de Virologie, Unité de Génétique Moléculaire des Virus à ARN (GMVR), Institut Pasteur, UMR3569, Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot, Sorbonne Paris Cité, Paris, France
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Yves Jacob
5Département de Virologie, Unité de Génétique Moléculaire des Virus à ARN (GMVR), Institut Pasteur, UMR3569, Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot, Sorbonne Paris Cité, Paris, France
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Frederick P. Roth
1Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
3Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada
4Donnelly Centre, University of Toronto, Toronto, Ontario, Canada
6Department of Computer Science, University of Toronto, Toronto, Ontario, Canada
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  • ORCID record for Frederick P. Roth
Brian Raught
2Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
7Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
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  • For correspondence: brian.raught@uhnres.utoronto.ca gingras@lunenfeld.ca
Anne-Claude Gingras
1Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
3Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada
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  • ORCID record for Anne-Claude Gingras
  • For correspondence: brian.raught@uhnres.utoronto.ca gingras@lunenfeld.ca
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Abstract

Viral replication is dependent on interactions between viral polypeptides and host proteins. Identifying virus-host protein interactions can thus uncover unique opportunities for interfering with the virus life cycle via novel drug compounds or drug repurposing. Importantly, many viral-host protein interactions take place at intracellular membranes and poorly soluble organelles, which are difficult to profile using classical biochemical purification approaches. Applying proximity-dependent biotinylation (BioID) with the fast-acting miniTurbo enzyme to 27 SARS-CoV-2 proteins in a lung adenocarcinoma cell line (A549), we detected 7810 proximity interactions (7382 of which are new for SARS-CoV-2) with 2242 host proteins (results available at covid19interactome.org). These results complement and dramatically expand upon recent affinity purification-based studies identifying stable host-virus protein complexes, and offer an unparalleled view of membrane-associated processes critical for viral production. Host cell organellar markers were also subjected to BioID in parallel, allowing us to propose modes of action for several viral proteins in the context of host proteome remodelling. In summary, our dataset identifies numerous high confidence proximity partners for SARS-CoV-2 viral proteins, and describes potential mechanisms for their effects on specific host cell functions.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://covid19interactome.org/

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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A SARS-CoV-2 – host proximity interactome
Payman Samavarchi-Tehrani, Hala Abdouni, James D.R. Knight, Audrey Astori, Reuben Samson, Zhen-Yuan Lin, Dae-Kyum Kim, Jennifer J. Knapp, Jonathan St-Germain, Christopher D. Go, Brett Larsen, Cassandra J. Wong, Patricia Cassonnet, Caroline Demeret, Yves Jacob, Frederick P. Roth, Brian Raught, Anne-Claude Gingras
bioRxiv 2020.09.03.282103; doi: https://doi.org/10.1101/2020.09.03.282103
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A SARS-CoV-2 – host proximity interactome
Payman Samavarchi-Tehrani, Hala Abdouni, James D.R. Knight, Audrey Astori, Reuben Samson, Zhen-Yuan Lin, Dae-Kyum Kim, Jennifer J. Knapp, Jonathan St-Germain, Christopher D. Go, Brett Larsen, Cassandra J. Wong, Patricia Cassonnet, Caroline Demeret, Yves Jacob, Frederick P. Roth, Brian Raught, Anne-Claude Gingras
bioRxiv 2020.09.03.282103; doi: https://doi.org/10.1101/2020.09.03.282103

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