An ancient influenza genome from Switzerland allows deeper insights into host adaptation during the 1918 flu pandemic in Europe

Abstract Background From 1918 to 1920, the largest influenza A virus (IAV) pandemic known to date spread globally causing between 20 to 100 million deaths. Historical records have captured critical aspects of the disease dynamics, such as the occurrence and severity of the pandemic waves. Yet, other...

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Main Authors: Christian Urban, Bram Vrancken, Livia V. Patrono, Ariane Düx, Mathilde Le Vu, Katarina L. Matthes, Nina Maria Burkhard-Koren, Navena Widulin, Thomas Schnalke, Sabina Carraro, Frank Rühli, Philippe Lemey, Kaspar Staub, Sébastien Calvignac-Spencer, Verena J. Schuenemann
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Language:English
Published: BMC 2025-07-01
Series:BMC Biology
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Online Access:https://doi.org/10.1186/s12915-025-02282-z
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author Christian Urban
Bram Vrancken
Livia V. Patrono
Ariane Düx
Mathilde Le Vu
Katarina L. Matthes
Nina Maria Burkhard-Koren
Navena Widulin
Thomas Schnalke
Sabina Carraro
Frank Rühli
Philippe Lemey
Kaspar Staub
Sébastien Calvignac-Spencer
Verena J. Schuenemann
author_facet Christian Urban
Bram Vrancken
Livia V. Patrono
Ariane Düx
Mathilde Le Vu
Katarina L. Matthes
Nina Maria Burkhard-Koren
Navena Widulin
Thomas Schnalke
Sabina Carraro
Frank Rühli
Philippe Lemey
Kaspar Staub
Sébastien Calvignac-Spencer
Verena J. Schuenemann
author_sort Christian Urban
collection DOAJ
description Abstract Background From 1918 to 1920, the largest influenza A virus (IAV) pandemic known to date spread globally causing between 20 to 100 million deaths. Historical records have captured critical aspects of the disease dynamics, such as the occurrence and severity of the pandemic waves. Yet, other important pieces of information such as the mutations that allowed the virus to adapt to its new host can only be obtained from IAV genomes. The analysis of specimens collected during the pandemic and still preserved in historical pathology collections can significantly contribute to a better understanding of its course. However, efficient RNA processing protocols are required to work with such specimens. Results Here, we describe an alternative protocol for efficient ancient RNA sequencing and evaluate its performance on historical samples, including a published positive control. The phenol/chloroform-free protocol efficiently recovers ancient viral RNA, especially small fragments, and maintains information about RNA fragment directionality through incorporating fragments by a ligation-based approach. One of the assessed historical samples allowed for the recovery of the first 1918 IAV genome from Switzerland. This genome, derived from a patient deceased during the beginning of the first pandemic wave in Switzerland, already harbours mutations linked to human adaptation. Conclusion We introduce an alternative, efficient workflow for ancient RNA recovery from formalin-fixed wet specimens. We also present the first precisely dated and complete influenza genome from Europe, highlighting the early occurrence of mutations associated with adaptation to humans during the first European wave of the 1918 pandemic.
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spelling doaj-art-844882cd61fe4aa48cfbca2c961f5feb2025-08-20T03:04:15ZengBMCBMC Biology1741-70072025-07-0123112210.1186/s12915-025-02282-zAn ancient influenza genome from Switzerland allows deeper insights into host adaptation during the 1918 flu pandemic in EuropeChristian Urban0Bram Vrancken1Livia V. Patrono2Ariane Düx3Mathilde Le Vu4Katarina L. Matthes5Nina Maria Burkhard-Koren6Navena Widulin7Thomas Schnalke8Sabina Carraro9Frank Rühli10Philippe Lemey11Kaspar Staub12Sébastien Calvignac-Spencer13Verena J. Schuenemann14Institute of Evolutionary Medicine, University of ZurichSpatial Epidemiology Lab (SpELL), Université Libre de BruxellesHelmholtz Institute for One HealthHelmholtz Institute for One HealthInstitute of Evolutionary Medicine, University of ZurichInstitute of Evolutionary Medicine, University of ZurichHerzpraxis Rapperswil-JonaBerlin Museum of Medical History, Charité - Universitätsmedizin BerlinBerlin Museum of Medical History, Charité - Universitätsmedizin BerlinInstitute of Evolutionary Medicine, University of ZurichInstitute of Evolutionary Medicine, University of ZurichDepartment of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven – University of LeuvenInstitute of Evolutionary Medicine, University of ZurichHelmholtz Institute for One HealthInstitute of Evolutionary Medicine, University of ZurichAbstract Background From 1918 to 1920, the largest influenza A virus (IAV) pandemic known to date spread globally causing between 20 to 100 million deaths. Historical records have captured critical aspects of the disease dynamics, such as the occurrence and severity of the pandemic waves. Yet, other important pieces of information such as the mutations that allowed the virus to adapt to its new host can only be obtained from IAV genomes. The analysis of specimens collected during the pandemic and still preserved in historical pathology collections can significantly contribute to a better understanding of its course. However, efficient RNA processing protocols are required to work with such specimens. Results Here, we describe an alternative protocol for efficient ancient RNA sequencing and evaluate its performance on historical samples, including a published positive control. The phenol/chloroform-free protocol efficiently recovers ancient viral RNA, especially small fragments, and maintains information about RNA fragment directionality through incorporating fragments by a ligation-based approach. One of the assessed historical samples allowed for the recovery of the first 1918 IAV genome from Switzerland. This genome, derived from a patient deceased during the beginning of the first pandemic wave in Switzerland, already harbours mutations linked to human adaptation. Conclusion We introduce an alternative, efficient workflow for ancient RNA recovery from formalin-fixed wet specimens. We also present the first precisely dated and complete influenza genome from Europe, highlighting the early occurrence of mutations associated with adaptation to humans during the first European wave of the 1918 pandemic.https://doi.org/10.1186/s12915-025-02282-zAncient RNAInfluenza A virus1918 flu pandemicAncient RNA method comparison
spellingShingle Christian Urban
Bram Vrancken
Livia V. Patrono
Ariane Düx
Mathilde Le Vu
Katarina L. Matthes
Nina Maria Burkhard-Koren
Navena Widulin
Thomas Schnalke
Sabina Carraro
Frank Rühli
Philippe Lemey
Kaspar Staub
Sébastien Calvignac-Spencer
Verena J. Schuenemann
An ancient influenza genome from Switzerland allows deeper insights into host adaptation during the 1918 flu pandemic in Europe
BMC Biology
Ancient RNA
Influenza A virus
1918 flu pandemic
Ancient RNA method comparison
title An ancient influenza genome from Switzerland allows deeper insights into host adaptation during the 1918 flu pandemic in Europe
title_full An ancient influenza genome from Switzerland allows deeper insights into host adaptation during the 1918 flu pandemic in Europe
title_fullStr An ancient influenza genome from Switzerland allows deeper insights into host adaptation during the 1918 flu pandemic in Europe
title_full_unstemmed An ancient influenza genome from Switzerland allows deeper insights into host adaptation during the 1918 flu pandemic in Europe
title_short An ancient influenza genome from Switzerland allows deeper insights into host adaptation during the 1918 flu pandemic in Europe
title_sort ancient influenza genome from switzerland allows deeper insights into host adaptation during the 1918 flu pandemic in europe
topic Ancient RNA
Influenza A virus
1918 flu pandemic
Ancient RNA method comparison
url https://doi.org/10.1186/s12915-025-02282-z
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