Major Shift of Influenza A Virus of Swine (IAV‐S) by Human‐to‐Swine Spillover of the 2009 Pandemic Virus in Korea

Figures

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  Figure 1. Maximum-likelihood (ML) phylogenetic trees and lineage classification of gene segments: HA-H1 (a), HA-H3 (b), NA-N1 (c), NA-N2 (d), and internal gene segments (e). Branches are colored by lineage of origin, and colored branch tips indicate strains isolated in this study, while reference strains are annotated with gray-colored tips. The tip shapes of triangles (human) and circles (swine) indicate the isolated host.

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  Figure 2. H1 and H3 swine influenza genotypes in Korea, 2004–2022. (a) Phylogenetic relationships of the H1Nx HAs. (b) Phylogenetic relationship of the H3Nx HAs. The MCC trees were reconstructed using the Bayesian evolutionary interference method. The phylogenetic branch tips with isolated hosts are color-labelled with light green (avian), dark blue (human), and dark red (swine). The branch tip labels with remarks are colored in pink (isolated in this study) and green (IAV-S vaccine used in Korea). The nodes correspond to the mean tMRCA, and the 95% HPD interval is represented with red boxes. Colored boxes show the lineage classification of each gene segment.

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  Figure 3. N1 and N2 swine influenza genotypes in Korea, 2004–2022. (a) Phylogenetic relationships of the HxN1 NAs. (b) Phylogenetic relationship of the HxN2 NAs. The MCC trees were reconstructed using the Bayesian evolutionary interference method. Branch tips, tip labels, and colored boxes are annotated in the same way as in Figure 2.

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  Figure 4. (a) Schematic representation of the genetic reassortment events that led to the development of the global A(H1N1)pdm09 pandemic and independent evolution of IAV-S in Korea. (b) Genotypes of IAV-S identified in Korea before (left) and after (right) introduction of Pdm09 into the swine population in 2009. (c) Proportional population shift of IAV-S genotypes in Korea within the periods 2004–2008 (before the 2009 pandemic), 2009–2014 (early post-2009 pandemic), and 2015–2022 (late post-2009 pandemic).

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  Figure 5. Amino acid mutations in Korean A(H1N1)pdm09 lineages. (a) Amino acid mutations in HA (H1). (b) Amino acid mutations in NA (N1). Known HA and NA antigenic sites are indicated in the tables. Dots denote positions with amino acid residues identical to the pdm09 vaccine strain A/California/07/2009. Green boxes denote positions with amino acid mutations identical to the World Health Organization (WHO)-recommended pdm09 vaccine strain A/Michigan/45/2015. Yellow boxes denote positions that are different from both vaccine strains.

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  Figure 6. Three-dimensional structure maps of the HA monomer of the A(H1N1)pdm09 strain A/California/04/2009 (protein data bank code: 3AL4) and recent Korean pdm09 clades showing antigenic sites and amino acid substitutions as well as predicted N-linked glycosylation patterns. Five antigenic sites at the globular head of the HA1 subunit, Sa (blue), Sb (red), Ca1 (cyan), Ca2 (yellow), and Cb (orange), are marked in the structure map of A/California/04/2009 in (a) lateral view and (b) top view. Amino acid mutations at antigenic sites of the pdm09 human clade, swine clade I and swine clade II HA1 subunits are marked with the colors mentioned above, and mutations at nonantigenic sites (wheat) are also colored. (c) Predicted N-linked glycosylation sites (purple) are marked in the structure map of A/California/04/2009. Additional predicted glycosylation sites of the pdm09 human clade, swine clade I and swine clade II HA1 subunits are marked (hot pink).

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  Figure 7. Sequence-based antigenic cartography of Korean and global swine or human H1 influenza A virus. (a) Viruses analyzed are represented as points colored according to their lineage or subclade. (b) Strains are represented as points colored and interconnected according to the assigned antigenic cluster. (c) Matrix of the mean between- and intercluster antigenic distances.