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PreprintCC BY-NCbioRxiv

Host type governs influenza evolutionary strategy across reservoir and spillover hosts

  1. 1University of Pennsylvania

Abstract

Despite its high propensity for host switching, the evolutionary mechanisms underlying influenza host adaptation remain unclear. H3Nx influenza viruses are uniquely generalist, with long-term lineages that circulate in avian, human, swine, equine, and canine hosts. Using 13,295 H3Nx sequences, we quantified host-specific adaptive evolution and developed a pipeline to map reassortment events onto trees with measures of statistical uncertainty. We find that while H3Nx viruses in mammals undergo adaptive evolution in HA and NA, viruses in birds experience very little directional selection. Instead, avian lineages exhibit high rates of reassortment, frequently generating novel reassortant lineages that persist transiently and turn over rapidly. 29.8-47.4% of all avian reassortant lineages are purged within the first year of circulation, and reassortment shows no fitness benefit in birds. In contrast, reassorted lineages in swine are more likely to persist long-term, suggesting that reassortment in swine may be broadly beneficial. Segment-specific reassortment patterns were also distinct between avian and mammalian viruses, with NA reassorting more frequently than expected in birds, but less frequently than expected in swine. Reassortment events are enriched between mammalian, but not avian, host switches, suggesting that reassortment may be most beneficial for mediating host switches among mammalian species. Together, our data suggest that host differences drive fundamentally different evolutionary outcomes for influenza viruses, transitioning from reassortment-dominant evolution in their avian reservoir, to varying degrees of adaptation upon establishment in mammals.

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BibTeX
@misc{maltepes2026host,
  title = {{Host type governs influenza evolutionary strategy across reservoir and spillover hosts}},
  author = {M. A. Maltepes and A. Markin and T. K. Anderson and K. Kistler and G. Park and L. Damodaran and J. Ort and J. Sabre and S. Shank and L. H. Moncla},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.15.751820},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.15.751820v1},
  note = {CC BY-NC},
}
RIS
TY  - UNPB
TI  - Host type governs influenza evolutionary strategy across reservoir and spillover hosts
AU  - M. A. Maltepes
AU  - A. Markin
AU  - T. K. Anderson
AU  - K. Kistler
AU  - G. Park
AU  - L. Damodaran
AU  - J. Ort
AU  - J. Sabre
AU  - S. Shank
AU  - L. H. Moncla
PY  - 2026
DA  - 2026/09/15
PB  - bioRxiv
DO  - 10.64898/2026.09.15.751820
UR  - https://www.biorxiv.org/content/10.64898/2026.09.15.751820v1
AB  - Despite its high propensity for host switching, the evolutionary mechanisms underlying influenza host adaptation remain unclear. H3Nx influenza viruses are uniquely generalist, with long-term lineages that circulate in avian, human, swine, equine, and canine hosts. Using 13,295 H3Nx sequences, we quantified host-specific adaptive evolution and developed a pipeline to map reassortment events onto trees with measures of statistical uncertainty. We find that while H3Nx viruses in mammals undergo adaptive evolution in HA and NA, viruses in birds experience very little directional selection. Instead, avian lineages exhibit high rates of reassortment, frequently generating novel reassortant lineages that persist transiently and turn over rapidly. 29.8-47.4% of all avian reassortant lineages are purged within the first year of circulation, and reassortment shows no fitness benefit in birds. In contrast, reassorted lineages in swine are more likely to persist long-term, suggesting that reassortment in swine may be broadly beneficial. Segment-specific reassortment patterns were also distinct between avian and mammalian viruses, with NA reassorting more frequently than expected in birds, but less frequently than expected in swine. Reassortment events are enriched between mammalian, but not avian, host switches, suggesting that reassortment may be most beneficial for mediating host switches among mammalian species. Together, our data suggest that host differences drive fundamentally different evolutionary outcomes for influenza viruses, transitioning from reassortment-dominant evolution in their avian reservoir, to varying degrees of adaptation upon establishment in mammals.
ER  -