Selective flexible packaging pathways of the segmented genome of influenza A virus

Ivan Haralampiev, Simon Prisner, Mor Nitzan, Matthias Schade, Fabian Jolmes, Max Schreiber, Maria Loidolt-Krüger, Kalle Jongen, Jasmine Chamiolo, Niklaas Nilson, Franziska Winter, Nir Friedman, Oliver Seitz, Thorsten Wolff () and Andreas Herrmann ()
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Ivan Haralampiev: IRI Life Sciences, Humboldt-Universität zu Berlin
Simon Prisner: IRI Life Sciences, Humboldt-Universität zu Berlin
Mor Nitzan: The Hebrew University of Jerusalem
Matthias Schade: IRI Life Sciences, Humboldt-Universität zu Berlin
Fabian Jolmes: IRI Life Sciences, Humboldt-Universität zu Berlin
Max Schreiber: Institute for Applied Informatics e.V. at Leipzig University
Maria Loidolt-Krüger: Max-Planck-Institute for Biophysical Chemistry
Kalle Jongen: IRI Life Sciences, Humboldt-Universität zu Berlin
Jasmine Chamiolo: Humboldt-Universität zu Berlin
Niklaas Nilson: IRI Life Sciences, Humboldt-Universität zu Berlin
Franziska Winter: Max-Planck-Institute for Biophysical Chemistry
Nir Friedman: The Hebrew University of Jerusalem
Oliver Seitz: Humboldt-Universität zu Berlin
Thorsten Wolff: Robert Koch Institut, Unit 17, Influenza and Other Respiratory Viruses
Andreas Herrmann: IRI Life Sciences, Humboldt-Universität zu Berlin

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract The genome of influenza A viruses (IAV) is encoded in eight distinct viral ribonucleoproteins (vRNPs) that consist of negative sense viral RNA (vRNA) covered by the IAV nucleoprotein. Previous studies strongly support a selective packaging model by which vRNP segments are bundling to an octameric complex, which is integrated into budding virions. However, the pathway(s) generating a complete genome bundle is not known. We here use a multiplexed FISH assay to monitor all eight vRNAs in parallel in human lung epithelial cells. Analysis of 3.9 × 105 spots of colocalizing vRNAs provides quantitative insights into segment composition of vRNP complexes and, thus, implications for bundling routes. The complexes rarely contain multiple copies of a specific segment. The data suggest a selective packaging mechanism with limited flexibility by which vRNPs assemble into a complete IAV genome. We surmise that this flexibility forms an essential basis for the development of reassortant viruses with pandemic potential.

Date: 2020
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DOI: 10.1038/s41467-020-18108-1

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