Proximity labelling of internalizing influenza A viruses reveals a role for neogenin in virus uptake.
Influenza A virus (IAV) is a respiratory pathogen of global concern. Entry of most IAVs is mediated by binding of viral hemagglutinin to cellular sialic acid, facilitating virus attachment. A subsequent interaction with a surface receptor(s) triggers viral uptake. Although multiple host factors invo...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-07-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1013338 |
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| author | Milagros Sempere Borau Victor G Gisbert Josephine von Kempis Laura M Arroyo-Fernández Samira Schiefer David Alsteens Silke Stertz |
| author_facet | Milagros Sempere Borau Victor G Gisbert Josephine von Kempis Laura M Arroyo-Fernández Samira Schiefer David Alsteens Silke Stertz |
| author_sort | Milagros Sempere Borau |
| collection | DOAJ |
| description | Influenza A virus (IAV) is a respiratory pathogen of global concern. Entry of most IAVs is mediated by binding of viral hemagglutinin to cellular sialic acid, facilitating virus attachment. A subsequent interaction with a surface receptor(s) triggers viral uptake. Although multiple host factors involved in viral entry are known, the identity of these receptors remains unclear. Here, we utilized proximity labelling to acquire the interactome of epsin 1, an adaptor protein utilized by IAV for clathrin-mediated endocytosis, during virus internalization to identify them. We uncover neogenin (Neo1), a member of the immunoglobulin superfamily expressed in primary human airway cultures, as a potential epsin 1 interactor and virus receptor candidate. Knockdown of Neo1 led to a reduction in replication of H1N1, H2N2 and H5N1 IAVs in primary and immortalized lung cells. Moreover, human recombinant Neo1 was found to bind IAV with a KD of 21 ± 14 nM by atomic force microscopy and Neo1 could co-localize with incoming IAV at early times post-infection, as well as affect viral entry. As Neo1 can interact with IAV and its depletion impairs IAV entry, this study reveals its potential as an IAV internalization receptor. |
| format | Article |
| id | doaj-art-6516bcb95c2b474b9cf23af8202df940 |
| institution | DOAJ |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-6516bcb95c2b474b9cf23af8202df9402025-08-20T02:39:48ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742025-07-01217e101333810.1371/journal.ppat.1013338Proximity labelling of internalizing influenza A viruses reveals a role for neogenin in virus uptake.Milagros Sempere BorauVictor G GisbertJosephine von KempisLaura M Arroyo-FernándezSamira SchieferDavid AlsteensSilke StertzInfluenza A virus (IAV) is a respiratory pathogen of global concern. Entry of most IAVs is mediated by binding of viral hemagglutinin to cellular sialic acid, facilitating virus attachment. A subsequent interaction with a surface receptor(s) triggers viral uptake. Although multiple host factors involved in viral entry are known, the identity of these receptors remains unclear. Here, we utilized proximity labelling to acquire the interactome of epsin 1, an adaptor protein utilized by IAV for clathrin-mediated endocytosis, during virus internalization to identify them. We uncover neogenin (Neo1), a member of the immunoglobulin superfamily expressed in primary human airway cultures, as a potential epsin 1 interactor and virus receptor candidate. Knockdown of Neo1 led to a reduction in replication of H1N1, H2N2 and H5N1 IAVs in primary and immortalized lung cells. Moreover, human recombinant Neo1 was found to bind IAV with a KD of 21 ± 14 nM by atomic force microscopy and Neo1 could co-localize with incoming IAV at early times post-infection, as well as affect viral entry. As Neo1 can interact with IAV and its depletion impairs IAV entry, this study reveals its potential as an IAV internalization receptor.https://doi.org/10.1371/journal.ppat.1013338 |
| spellingShingle | Milagros Sempere Borau Victor G Gisbert Josephine von Kempis Laura M Arroyo-Fernández Samira Schiefer David Alsteens Silke Stertz Proximity labelling of internalizing influenza A viruses reveals a role for neogenin in virus uptake. PLoS Pathogens |
| title | Proximity labelling of internalizing influenza A viruses reveals a role for neogenin in virus uptake. |
| title_full | Proximity labelling of internalizing influenza A viruses reveals a role for neogenin in virus uptake. |
| title_fullStr | Proximity labelling of internalizing influenza A viruses reveals a role for neogenin in virus uptake. |
| title_full_unstemmed | Proximity labelling of internalizing influenza A viruses reveals a role for neogenin in virus uptake. |
| title_short | Proximity labelling of internalizing influenza A viruses reveals a role for neogenin in virus uptake. |
| title_sort | proximity labelling of internalizing influenza a viruses reveals a role for neogenin in virus uptake |
| url | https://doi.org/10.1371/journal.ppat.1013338 |
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