Morphology-dependent entry kinetics and spread of influenza A virus
Influenza A viruses (IAV) display a broad variety of morphologies ranging from spherical to long filamentous virus particles. These diverse phenotypes are believed to allow the virus to overcome various immunological and pulmonary barriers during entry into the airway epithelium, and to influence the viral entry pathway. Notably, laboratory-adapted IAV strains predominantly adopt a spherical form, yet the factors driving this preference as well as the factors favoring filamentous morphology in physiological settings remain unclear. To address this, we generated fluorescent reporter viruses with identical surface glycoproteins but distinct morphologies and developed a correlative light and scanning electron microscopy workflow. This enabled us to investigate the impact of viral morphology on spread, and to identify conditions favoring either form. Our findings demonstrate that filamentous IAV spread significantly slower in various cell lines, consistent with delayed entry kinetics and in-cell cryo-electron tomography, explaining the predominance of spherical forms in laboratory-adapted strains. Cellular junction integrity, neuraminidase activity, and mucin do not inhibit IAV spread in a morphology-dependent manner. However, filamentous virions confer a selective advantage under neutralizing-antibody pressure against hemagglutinin.
Authors
- Sarah Peterl (ORCID: https://orcid.org/0000-0002-8082-3546)
- Petr Chlanda (ORCID: https://orcid.org/0000-0002-7782-2139)
- Maria Villiou (ORCID: https://orcid.org/0000-0001-8966-3852)
- Charlotta Funaya (ORCID: https://orcid.org/0000-0003-1375-1287)
- Christine Selhuber‐Unkel (ORCID: https://orcid.org/0000-0002-5051-4822)
- Frederik Graw (ORCID: https://orcid.org/0000-0002-1198-6632)
- Karl Rohr (ORCID: https://orcid.org/0000-0001-7673-0999)
- Steffen Klein (ORCID: https://orcid.org/0000-0002-8046-0474)
- Elisabetta Ada Cavalcanti‐Adam (ORCID: https://orcid.org/0000-0003-0243-1552)
- Carmen Maria Lahr (ORCID: https://orcid.org/0000-0001-9689-6232)
- Xenia Podlipensky
- Vera Lechner
- Larissa Eis
- Janis Meyer
- Carl Niklas Schneider
Institutions
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- University of Luxembourg (LU)
- Heidelberg University (DE)
- University Hospital Heidelberg (DE)
- Max Planck Institute for Medical Research (DE)
- Universitätsklinikum Erlangen (DE)
- Max Planck Institute for Polymer Research (DE)
- European Molecular Biology Laboratory (DE)
- European Molecular Biology Laboratory (DE)
- University of Bayreuth (DE)
Publication Details
- Journal
- The EMBO Journal
- Published
- 2025-06-09
- DOI
- https://doi.org/10.1038/s44318-025-00481-6
- Citations
- 2
- Primary Topic
- Influenza Virus Research Studies
- Type
- article
- Field-Weighted Citation Impact
- 2.71
Funders
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- Daimler und Benz Stiftung
- Chica and Heinz Schaller Foundation
- European Research Council