Genetic and antigenic characterization of an expanding H3 influenza A virus clade in US swine visualized by Nextstrain
Defining factors that influence spatial and temporal patterns of influenza A virus (IAV) is essential to inform vaccine strain selection and strategies to reduce the spread of potentially zoonotic swine-origin IAV. The relative frequency of detection of the H3 phylogenetic clade 1990.4.a (colloquially known as C-IVA) in US swine declined to 7% in 2017, but increased to 32% in 2019. We conducted phylogenetic and phenotypic analyses to determine putative mechanisms associated with increased detection. We created an implementation of Nextstrain to visualize the emergence, spatial spread, and genetic evolution of H3 IAV-S, identifying two C-IVA clades that emerged in 2017 and cocirculated in multiple US states. Phylodynamic analysis of the HA gene documented low relative genetic diversity from 2017 to 2019, suggesting clonal expansion. The major H3 C-IVA clade contained an N156H amino acid substitution, but HI assays demonstrated no significant antigenic drift. The minor HA clade was paired with the NA clade N2-2002B prior to 2016, but acquired and maintained N2-2002A in 2016, resulting in a loss in antigenic cross-reactivity between N2-2002B and -2002A containing H3N2 strains. The major C-IVA clade viruses acquired a nucleoprotein (NP) of the H1N1pdm09 lineage through reassortment in replacement of the North American swine lineage NP. Instead of genetic or antigenic diversity within the C-IVA HA, our data suggest that population immunity to H3 2010.1, along with antigenic diversity of the NA and acquisition of the H1N1pdm09 NP gene likely explain the re-emergence and transmission of C-IVA H3N2 in swine.