The Pillar of Fire, Tintoretto (1577 - 1578)

 

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Public Domain.

Source: 

Link: https://www.wikiart.org/en/tintoretto/the-pillar-of-fire-1578

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#MHC-II acts as a #fusion-triggering #receptor for #bat #influenza virus

 

Abstract

Influenza A virus hemagglutinin is a prototypical class I viral fusion protein that binds sialylated glycans and is activated by low pH in endosomes. In contrast, bat-derived IAV subtypes H17N10 and H18N11 use major histocompatibility complex class II (MHC-II) as an entry receptor, but how this receptor contributes to membrane fusion remains unknown. We find that MHC-II-dependent hemagglutinin subtypes H17, H18, and H19 possess an increased negative net charge relative to canonical HAs. Using cryo-electron tomography, we demonstrate that H18N11 morphology remains stable and H18 is in prefusion conformation at strongly acidic pH. Remarkably, H18 undergoes fusion-relevant conformational changes only when both MHC-II binding and low pH are present. By reconstitution of H18N11 fusion with liposomes and purified MHC-II, we show that receptor engagement is required to trigger the fusion activity of H18. These findings identify MHC-II as a receptor that directly triggers membrane fusion and reveal a previously unrecognized receptor-dependent mechanism of influenza virus entry.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Deutsche Forschungsgemeinschaft, https://ror.org/018mejw64, 240245660 – P19, 537227910

European Research Council, 882631—Bat Flu

Excellence Initiative of the German Research Foundation, GSC-4, Spemann Graduate School

Hans A. Krebs Medical Scientist Programme

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.07.08.737388v1

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Lactylation of #Influenza Virus #Polymerase Acidic Protein Promotes Viral #Replication and #Pathogenicity

 

Abstract

Influenza virus poses a potential risk of triggering the next global pandemic. In-depth investigation into the mechanisms underlying influenza virus replication and pathogenicity will provide robust support for controlling influenza virus infection. Although post-translational modifications are known to regulate viral infection, the role of lactylation in influenza virus replication remains elusive. In this study, influenza virus ribonucleoprotein complex subunits are found to be lactylated. Specifically, ATAT1 promotes viral polymerase acidic protein (PA) lactylation and enhances viral replication. In contrast, SIRT1 mediates de-lactylation of PA and exerts an inhibitory effect on viral replication. Further investigations reveal lactylation of PA at residues K605 and K609 is essential for viral replication and pathogenicity. Mechanistically, PA K605/609 residues are localized at the interaction interface of the ANP32-mediated polymerase asymmetric dimer; mutation at these residues inhibits polymerase asymmetric dimerization, thereby impairing RNA production during viral genome replication. Collectively, this study uncovers a novel mechanism by which influenza virus hijacks host enzymes to mediate PA lactylation, and expands the molecular regulatory network of influenza virus infection.

Competing Interest Statement

The authors have declared no competing interest.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.07.10.737663v1

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