Identification of host cell surface proteins inhibiting furin dependent proteolytic processing of viral glycoproteins

Article Article scientifique Article Identification of host cell surface proteins inhibiting furin dependent proteolytic processing of viral glycoproteins eng 2025-07-15 2025-07-15 author Williams Nathalia 0000-0003-2279-5302 Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 942117 author Chabert-Ben Cherifa Mehdi Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 410694 Département de microbiologie et médecine moléculaire (MIMOL) author Besomi Alicia Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 873488 author Silva Filo Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 23504 Département de microbiologie et médecine moléculaire (MIMOL) author Sobiech Karolina Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 409200 Département de microbiologie et médecine moléculaire (MIMOL) author Schmolke Mirco 0000-0002-2491-3029 Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland. mirco.schmolke@unige.ch.,Geneva Center for Inflammation Research, University of Geneva, Geneva, Switzerland. mirco.schmolke@unige.ch. 821513 Département de microbiologie et médecine moléculaire (MIMOL) 25454 10.1038/s41598-025-11164-x 40659811 2045-2322 PMC12259872 https://www.nature.com/articles/s41598-025-11164-x Proteolytic cleavage by furin-like proteases is a crucial first step in the posttranslational modification of various glycoproteins found in enveloped emerging viruses, such as SARS-CoV-2 and highly pathogenic avian influenza A viruses (IAV). Here, we explored the capacity of host cell proteins identified by cell surface proximity ligation to limit the proteolytic cleavage of the SARS-CoV-2 spike and the IAV H5N1 hemagglutinin (HA). When co-expressed with recombinant SARS-CoV-2 spike protein, Prom1, Axl, and Ly75 suppress its proteolytic cleavage, whereas cleavage of HA was only reduced by Prom1. Co-immunoprecipitation assays suggest that Axl and Prom1 may form a complex with furin. Alteration of Prom1, Axl and Ly75 expression levels in Calu3 cells affected entry of SARS-CoV-2 S pseudotyped VLP and to a lesser extent, SARS-CoV-2 virions. In contrast, Prom1 levels did not affect entry of H5N1 VLPs or H5N1 virions. Our data highlight the differential capacity of SARS-CoV-2 and IAV H5N1 to cope with newly identified host restriction factors of furin activity. Furin / metabolism Humans Spike Glycoprotein, Coronavirus / metabolism Spike Glycoprotein, Coronavirus / genetics Proteolysis SARS-CoV-2 / metabolism SARS-CoV-2 / physiology Influenza A Virus, H5N1 Subtype / metabolism Hemagglutinin Glycoproteins, Influenza Virus / metabolism Membrane Proteins / metabolism Virus Internalization Cell Line COVID-19 / virology COVID-19 / metabolism Receptor Protein-Tyrosine Kinases / metabolism Receptor Protein-Tyrosine Kinases / genetics HEK293 Cells Animals Proto-Oncogene Proteins / metabolism Proto-Oncogene Proteins / genetics Dewey 616 Swiss National Science Foundation Directed search for host surface proteins as antiviral targets against SARS-CoV-2 196330 CH Programmes Swiss National Science Foundation Identification and characterization of host factors affecting Inter-and intra-species spreading of influenza A viruses 212216 CH Projects 54 Département de microbiologie et médecine moléculaire 21B false 912 Modulation de la flore microbienne dans un hôte infecté par un virus 947 Scientific reports 15 1 05d25158-2d1c-4fec-984e-94a3251a5014 Article (Published version) Public Article_scientifique_from_europePmc.pdf 4766610 application/pdf CC BY-4.0 1572f7ebfb444e1d7201617d66cd519ebe2aa8738bf556e6112b2c0eeb929b25 9a43d4b5-33a3-4346-9e2f-680a0a548484 Appendix Public 41598_2025_11164_MOESM1_ESM.pdf 2590295 application/pdf 3e144c04750939c1e7af3232f439cce8712b47fcb94bc0dcc4772602ae5f792d 11905de7-380a-4ba5-8797-e0727b2b0ee9 Appendix Public 41598_2025_11164_MOESM2_ESM.pdf 1878926 application/pdf 8d45f5a0192544685febb16cf79a32a55704fce9388937c59d0d1effaf0ce286 69ffdfbd-0820-4c63-9596-29af579a1962 Appendix Public 41598_2025_11164_MOESM3_ESM.pdf 190113 application/pdf 517b7019dd431896cc8fc5ff68075557badd085c4c9171ca0f1363398ca9ad15 587ada7f-5a69-4e84-bb9d-7fa4a18bf2fe Appendix Public 41598_2025_11164_MOESM4_ESM.pdf 32401 application/pdf cfdad9855e585e436bd898dabe6d095102c19a8e0cf96fef5afc71970516418f a8c3151c-191b-4e28-bc79-86b67aafaf85 Appendix Public 41598_2025_11164_MOESM5_ESM.pdf 54652 application/pdf 880d771d59414948ada26ee2c6dd8a62836328a869a80d78638fc6d25077bfa6 8c2356bb-5cdf-4304-b6da-a13706ad5b79 Appendix Public 41598_2025_11164_MOESM6_ESM.pdf 37459 application/pdf 8ce7edbb29206c6c2bce19e793220f7dd3a2592d166e879df89faa72cc6da195 5d38aa4c-8615-4412-945b-16badc8f2f6d Appendix Public 41598_2025_11164_MOESM7_ESM.pdf 105102 application/pdf 9a23d8e1469d1e1031a60d5c7aa8acafa82a340d8f8ff9993e6b06a2e5a464bb d29b7695-fcde-446e-afc2-f95fe377b2d7 Appendix Public 41598_2025_11164_MOESM8_ESM.pdf 7896595 application/pdf 1b209b2b03475b9a790260b2b5820621b2723c0f7fdffcae78d797f545580162 openAccess Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire

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Identification of host cell surface proteins inhibiting furin dependent proteolytic processing of viral glycoproteins	Scientific reports	2025	65	32
Characterization of new host cell surface protein affecting SARS-CoV-2 entry		2023	96	5

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