Fig 1.
A conceptual model describing the human-swine interface and zoonotic risk for the 2009 H1N1 pandemic lineage (pdm09).
There is a linear correlation between the burden of pdm09 in human populations and the number of reverse-zoonoses; a subset of these spillovers (indicated by smaller arrow width) persists for multiple years in pigs, evolve, and drift from the founding human-origin pdm09 strain; occasionally these persistent pdm09 cause zoonotic infections. These patterns were derived from pdm09 dynamics in the US. Created with BioRender.com.
Fig 2.
Time-scaled phylogeny of 13,935 swine and human hemagglutinin (HA) genes within the 2009 H1N1 pandemic lineage (pdm09) collected between 2009 and 2021.
Orange branches indicate evolution in swine and black branches in humans. Human H1N1pdm09 seasonal clade names are annotated and clade defining amino acid mutations and those associated with antigenic change are annotated across the trunk of the phylogeny.
Fig 3.
The spatial-temporal dynamics of swine H1pdm09 detections driven by human-to-swine spillovers.
A. Number of swine pdm09 sequences from 2010–11 to 2020–21 seasons with colors indicating the inferred season of spillover. B. The detection propotion of swine H1pdm09 detections relative to the other swine H1 clades in the USDA Influenza A Virus in swine surveillance system. C. Spatial distribution of human-to-swine pdm09 spillovers. The spatial distribution map was made with the Plotly graphing library for Python https://github.com/plotly/plotly.py.
Table 1.
The number of human-to-swine spillovers grouped by season.
Fig 4.
Association between human and swine H1pdm09 detection frequency.
A. H1N1pdm09 detections in humans and swine for each season between 2010–11 and 2019–20. The linear regression line was fitted with ordinary least squares and each blue dot is labeled by the corresponding influenza season. The 2020–21 season was omitted due to low detection of H1N1pdm09 in human populations. B. The number of interspecies transmission events grouped by influenza season and host origin, human-to-swine (hu-to-sw) in orange and swine-to-human (sw-to-hu) in black.
Fig 5.
Rule mining to determine the host origin of H1N1pdm09 in swine measured in similarity in the hemagglutinin (HA) gene.
A. Swine HA sequences collected between the 2013–14 and 2019–20 seasons (inclusively) were colored red (open circle) if it was collected in season S and was derived from a human-to-swine spillover that happened in same season S. These data were colored blue (solid circle) if they reflected onward transmission of endemic swine pdm09 clades. The x-axis indicates the maximum similarity to a human HA sequence collected in season S-1 and the y-axis reflects maximum similarity to a swine HA sequence from season S-1. All same-season human-to-swine transmission events (open red circles) are located below the diagonal. B. The 2020–21 season swine HA sequences plotted using the same genetic similarity thresholds with most data located above the diagonal reflecting onward transmission of endemic pdm09 in swine.
Fig 6.
Subtrees extracted from an H1N1pdm09 phylogeny of 13,935 hemagglutinin (HA) genes demonstrating evidence for zoonoses.
Swine HA genes are colored in orange and human HA genes are colored in black. Amino acid substitutions associated with phenotypic change are annotated on the tree edges. A. Human HA genes, A/North Carolina/01/2021 and A/Iowa/01/2021, nested within a clade of 2019–20 and 2020–21 swine pdm09 HAs. B. Human HA genes, A/Iowa/22/2020 and A/Iowa/23/2020, nested within a clade of 2019–20 swine pdm09 HAs. Edge lengths represent sequence divergence, and all displayed edges had 100% bootstrap support.
Fig 7.
Hemagglutinin inhibition of contemporary swine pdm09 strains by pdm09 seasonal vaccine ferret antisera.
The graph shows the antigenic distances as log2 of the ratio of homologous/heterologous geometric mean reciprocal titers. Three units of antigenic distance is equivalent to an 8-fold loss in HI cross-reactivity.