The bat influenza A virus subtype H18N11 induces nanoscale MHCII clustering upon host cell attachment
Abstract Prior to the discovery of bat influenza A virus (IAV) subtypes H17N10 and H18N11, all IAVs were thought to bind sialic acid residues via hemagglutinin (HA) to mediate attachment and subsequent viral entry. However, H17 and H18 engage a proteinaceous receptor: the major histocompatibility co...
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Nature Portfolio
2025-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-58834-y |
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| author | Maria Kaukab Osman Jonathan Robert Lukas Broich Dennis Frank Robert Grosse Martin Schwemmle Antoni G. Wrobel Kevin Ciminski Christian Sieben Peter Reuther |
| author_facet | Maria Kaukab Osman Jonathan Robert Lukas Broich Dennis Frank Robert Grosse Martin Schwemmle Antoni G. Wrobel Kevin Ciminski Christian Sieben Peter Reuther |
| author_sort | Maria Kaukab Osman |
| collection | DOAJ |
| description | Abstract Prior to the discovery of bat influenza A virus (IAV) subtypes H17N10 and H18N11, all IAVs were thought to bind sialic acid residues via hemagglutinin (HA) to mediate attachment and subsequent viral entry. However, H17 and H18 engage a proteinaceous receptor: the major histocompatibility complex class II (MHCII). The mechanistic details of this hitherto unknown protein-mediated entry are not understood. Given that conventional IAVs rely on multivalent binding to sialylated glycans, we hypothesized that bat HA similarly interacts with multiple MHCII molecules. Using photoactivated localization microscopy (PALM) on fixed and live cells, we demonstrate that bat IAV particles attach to pre-existing MHCII clusters and induce a further increase in cluster size upon binding. To measure the impact of viral attachment on the dynamics of MHCII, we employ an “inverse attachment” approach, immobilizing viral particles on coverslips before seeding live MHCII-expressing cells on top. Single-molecule tracking reveals that the mobility of MHCII is indeed slowed down in viral proximity leading to a local enrichment of MHCII molecules beneath the viral particle. These findings suggest that viral attachment induces MHCII clustering, a process similar to the MHCII dynamics observed during the formation of an immunological synapse. |
| format | Article |
| id | doaj-art-ca7c19e253ac414aabda2f5072e7cffe |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
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| series | Nature Communications |
| spelling | doaj-art-ca7c19e253ac414aabda2f5072e7cffe2025-08-20T03:15:12ZengNature PortfolioNature Communications2041-17232025-04-0116111110.1038/s41467-025-58834-yThe bat influenza A virus subtype H18N11 induces nanoscale MHCII clustering upon host cell attachmentMaria Kaukab Osman0Jonathan Robert1Lukas Broich2Dennis Frank3Robert Grosse4Martin Schwemmle5Antoni G. Wrobel6Kevin Ciminski7Christian Sieben8Peter Reuther9Institute of Virology, Medical Center—University of FreiburgInstitute of Virology, Medical Center—University of FreiburgNanoscale Infection Biology Group, Department of Cell Biology, Helmholtz Centre for Infection ResearchInstitute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty, University of FreiburgInstitute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty, University of FreiburgInstitute of Virology, Medical Center—University of FreiburgStructural Biology of Disease Processes Laboratory, The Francis Crick InstituteInstitute of Virology, Medical Center—University of FreiburgNanoscale Infection Biology Group, Department of Cell Biology, Helmholtz Centre for Infection ResearchInstitute of Virology, Medical Center—University of FreiburgAbstract Prior to the discovery of bat influenza A virus (IAV) subtypes H17N10 and H18N11, all IAVs were thought to bind sialic acid residues via hemagglutinin (HA) to mediate attachment and subsequent viral entry. However, H17 and H18 engage a proteinaceous receptor: the major histocompatibility complex class II (MHCII). The mechanistic details of this hitherto unknown protein-mediated entry are not understood. Given that conventional IAVs rely on multivalent binding to sialylated glycans, we hypothesized that bat HA similarly interacts with multiple MHCII molecules. Using photoactivated localization microscopy (PALM) on fixed and live cells, we demonstrate that bat IAV particles attach to pre-existing MHCII clusters and induce a further increase in cluster size upon binding. To measure the impact of viral attachment on the dynamics of MHCII, we employ an “inverse attachment” approach, immobilizing viral particles on coverslips before seeding live MHCII-expressing cells on top. Single-molecule tracking reveals that the mobility of MHCII is indeed slowed down in viral proximity leading to a local enrichment of MHCII molecules beneath the viral particle. These findings suggest that viral attachment induces MHCII clustering, a process similar to the MHCII dynamics observed during the formation of an immunological synapse.https://doi.org/10.1038/s41467-025-58834-y |
| spellingShingle | Maria Kaukab Osman Jonathan Robert Lukas Broich Dennis Frank Robert Grosse Martin Schwemmle Antoni G. Wrobel Kevin Ciminski Christian Sieben Peter Reuther The bat influenza A virus subtype H18N11 induces nanoscale MHCII clustering upon host cell attachment Nature Communications |
| title | The bat influenza A virus subtype H18N11 induces nanoscale MHCII clustering upon host cell attachment |
| title_full | The bat influenza A virus subtype H18N11 induces nanoscale MHCII clustering upon host cell attachment |
| title_fullStr | The bat influenza A virus subtype H18N11 induces nanoscale MHCII clustering upon host cell attachment |
| title_full_unstemmed | The bat influenza A virus subtype H18N11 induces nanoscale MHCII clustering upon host cell attachment |
| title_short | The bat influenza A virus subtype H18N11 induces nanoscale MHCII clustering upon host cell attachment |
| title_sort | bat influenza a virus subtype h18n11 induces nanoscale mhcii clustering upon host cell attachment |
| url | https://doi.org/10.1038/s41467-025-58834-y |
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