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Morphology-dependent entry kinetics and spread of influenza A virus

par Sarah Peterl, Carmen M. Lahr, Carl N. Schneider, Janis Meyer, Xenia Podlipensky, Vera Lechner, Maria Villiou, Larissa Eis, Steffen Klein, Charlotta Funaya, Elisabetta Ada Cavalcanti-Adam, Frederik Graw, Christine Selhuber-Unkel, Karl Rohr et Petr Chlanda

Publié: 1 août 2024
Serveur de preprints: bioRxiv
DOI: 10.1101/2024.08.01.605992

Résumé

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 influence the viral entry pathway. Remarkably, lab-adapted IAV strains lost this morphological variance and exhibit preferred spherical morphology. However, it remains unclear which factors lead to this lab-adapted preference and which pulmonary defense factors are responsible for the preferred filamentous morphology in physiological settings. In this study, we established fluorescent reporter viruses with spherical or filamentous morphology but with the same surface glycoproteins. We developed a correlative fluorescence and scanning electron microscopy workflow to analyze the impact of viral morphology on cell-to-cell spread and identify conditions under which IAV with either spherical or filamentous morphology confer an advantage. Our findings demonstrate that filamentous IAV cell-to-cell spread is significantly slower in various cell lines, which can explain the predominant spherical morphology in lab-adapted strains. This observation is consistent with delayed entry kinetics of filamentous viruses structurally analyzed by cellular cryo-electron tomography. We found that cellular junction integrity and mucin do not exert morphology-dependent inhibition of IAV cell-to-cell spread. On the other hand, filamentous virions confer an advantage under the pressure exerted by neutralizing antibodies against hemagglutinin.

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PREreview par Craig McCormick

Rédigé par Craig McCormick

We, the students of MICI5029/5049, a Graduate Level Molecular Pathogenesis Journal Club at Dalhousie University in Halifax, NS, Canada, hereby submit a review of the following BioRxiv preprint:

Morphology-dependent entry kinetics and spread of influenza A virus
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