Identification of host cell surface proteins inhibiting furin dependent proteolytic processing of viral glycoproteins
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| Názov: | Identification of host cell surface proteins inhibiting furin dependent proteolytic processing of viral glycoproteins |
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| Autori: | Williams, Nathalia, Chabert-Ben Cherifa, Mehdi, Besomi, Alicia, Silva, Filo, Sobiech, Karolina, Schmolke, Mirco |
| Zdroj: | Sci Rep |
| Informácie o vydavateľovi: | Springer Science and Business Media LLC, 2025. |
| Rok vydania: | 2025 |
| Predmety: | COVID-19 / metabolism, COVID-19 / virology, Influenza A Virus, H5N1 Subtype / metabolism, Spike Glycoprotein, Coronavirus / genetics, Proto-Oncogene Proteins / metabolism, Receptor Protein-Tyrosine Kinases / metabolism, Virus Internalization, Membrane Proteins / metabolism, Article, SARS-CoV-2 / physiology, Cell Line, Furin / metabolism, Spike Glycoprotein, Coronavirus / metabolism, Receptor Protein-Tyrosine Kinases / genetics, HEK293 Cells, Hemagglutinin Glycoproteins, Influenza Virus / metabolism, Proteolysis, Humans, Animals, SARS-CoV-2 / metabolism, Proto-Oncogene Proteins / genetics |
| Popis: | 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. |
| Druh dokumentu: | Article Other literature type |
| Popis súboru: | application/pdf |
| Jazyk: | English |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-025-11164-x |
| Rights: | CC BY |
| Prístupové číslo: | edsair.doi.dedup.....435ed2b1f9e946eb5ad7885cf840bc97 |
| Databáza: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | 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. |
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| ISSN: | 20452322 |
| DOI: | 10.1038/s41598-025-11164-x |