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IL4I1 binds to TMPRSS13 and competes with SARS-Cov2 Spike

Jérôme Gatineau, Charlotte Nidercorne, Aurélie Dupont, Marie-Line Puiffe, José L Cohen, Valérie Molinier-Frenkel, Florence Niedergang, Flavia Castellano
doi: https://doi.org/10.1101/2021.12.23.473686
Jérôme Gatineau
1Univ Paris Est Creteil, INSERM, IMRB, F-94010 Creteil, France
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Charlotte Nidercorne
4Université de Paris, Institut Cochin, INSERM, CNRS, F-75014 Paris, France
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Aurélie Dupont
1Univ Paris Est Creteil, INSERM, IMRB, F-94010 Creteil, France
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Marie-Line Puiffe
1Univ Paris Est Creteil, INSERM, IMRB, F-94010 Creteil, France
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José L Cohen
1Univ Paris Est Creteil, INSERM, IMRB, F-94010 Creteil, France
2AP-HP, Hopital H Mondor, CIC Biotherapies, Créteil 94010, France
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Valérie Molinier-Frenkel
1Univ Paris Est Creteil, INSERM, IMRB, F-94010 Creteil, France
3AP-HP, Hopital Henri Mondor, Departement d’Hematologie-Immunologie, Créteil 94010, France
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  • For correspondence: flavia.castellano@inserm.fr florence.niedergang@inserm.fr valerie.frenkel@inserm.fr
Florence Niedergang
4Université de Paris, Institut Cochin, INSERM, CNRS, F-75014 Paris, France
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  • For correspondence: flavia.castellano@inserm.fr florence.niedergang@inserm.fr valerie.frenkel@inserm.fr
Flavia Castellano
1Univ Paris Est Creteil, INSERM, IMRB, F-94010 Creteil, France
5AP-HP, Hopital Henri Mondor, Plateforme des Ressources Biologiques, Créteil 94010, France
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  • For correspondence: flavia.castellano@inserm.fr florence.niedergang@inserm.fr valerie.frenkel@inserm.fr
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Abstract

The secreted enzyme interleukin four-induced gene 1 (IL4I1) is involved in the negative control of the adaptive immune response. IL4I1 expression in human cancer is frequent and correlates with poor survival and resistance to immunotherapy. Nevertheless, its mechanism of action remains partially unknown. Here, we identified transmembrane serine protease 13 (TMPRSS13) as an immune cell-expressed surface protein that binds IL4I1. TMPRSS13 is a paralog of TMPRSS2, whose protease activity participates in the cleavage of SARS-Cov2 Spike protein and facilitates virus induced-membrane fusion. We show that TMPRSS13 is expressed by human lymphocytes, monocytes and monocyte-derived macrophages, can cleave the Spike protein and allow Sars-Cov2 Spike pseudotyped virus entry into cells. We identify regions of homology between IL4I1 and Spike and demonstrate competition between the two proteins for TMPRSS13 binding. These findings may be relevant for both interfering with SARS-Cov2 infection and limiting IL4I1-dependent immunosuppressive activity in cancer.

One-Sentence Summary Through binding to its newly identified receptor TMPRSS13, the enzyme IL4I1 interferes with SARS-Cov2 Spike cleavage thereby blocking viral entry into host cells.

Competing Interest Statement

The authors have declared no competing interest.

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Posted December 25, 2021.
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IL4I1 binds to TMPRSS13 and competes with SARS-Cov2 Spike
Jérôme Gatineau, Charlotte Nidercorne, Aurélie Dupont, Marie-Line Puiffe, José L Cohen, Valérie Molinier-Frenkel, Florence Niedergang, Flavia Castellano
bioRxiv 2021.12.23.473686; doi: https://doi.org/10.1101/2021.12.23.473686
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IL4I1 binds to TMPRSS13 and competes with SARS-Cov2 Spike
Jérôme Gatineau, Charlotte Nidercorne, Aurélie Dupont, Marie-Line Puiffe, José L Cohen, Valérie Molinier-Frenkel, Florence Niedergang, Flavia Castellano
bioRxiv 2021.12.23.473686; doi: https://doi.org/10.1101/2021.12.23.473686

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