Genetic and antigenic characterization of an expanding H3 influenza A virus clade in US swine visualized by Nextstrain

Authors: NEVEAU, MEGAN - Iowa State University; ZELLER, MICHAEL - Iowa State University; KAPLAN, BRYAN - Orise Fellow; SOUZA, CARINE - Orise Fellow; GAUGER, PHILLIP - Iowa State University; Baker, Amy; Anderson, Tavis

Submitted to: bioRxiv
Publication Type: Pre-print Publication
Publication Acceptance Date: 11/19/2021
Publication Date: 11/19/2021
Citation: Neveau, M.N., Zeller, M.A., Kaplan, B.S., Souza, C.K., Gauger, P.C., Baker, A.L., Anderson, T.K. 2021. Genetic and antigenic characterization of an expanding H3 influenza A virus clade in US swine visualized by Nextstrain. bioRxiv. https://doi.org/10.1101/2021.11.17.469008.
DOI: https://doi.org/10.1101/2021.11.17.469008

Interpretive Summary: The existence of genetically distinct clades of influenza A virus in swine (IAV-S) undermines efforts to control the disease. Swine producers commonly use vaccines to control the virus, and their components are typically selected by identifying the most common clade in a farm or a region. In 2019, we identified an increase in detection frequency of an H3 subtype phylogenetic clade, C-IVA, in U.S. swine, which was previously circulating at low levels. Our study identified genetic and antigenic factors contributing to its resurgence by linking comprehensive phylodynamic analyses with empirical wet-lab experiments and visualized these evolutionary analyses in a Nextstain for IAV-S implementation. We demonstrated that the contemporary C-IVA viruses did not have a prior increase in genetic diversity nor significant HA or NA antigenic changes. Instead, many of the contemporary C-IVA viruses acquired a nucleoprotein (NP) gene segment via reassortment that might have contributed to the clade’s success.

Technical Abstract: Defining factors that influence spatial and temporal patterns in the diversity of influenza A virus in swine (IAV-S) 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 CIV-A in US swine declined to 7% in 2017, but increased to 32% in 2019. We conducted phylogenetic and phenotypic analyses of representative strains to determine putative mechanisms associated with increased detection. We created an IAV-S implementation of Nextstrain to visualize the emergence, spatial spread, and genetic evolution of H3 IAV-S. These analyses identified 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 clade was associated with an N156H amino acid substitution, although HI assays demonstrated no significant antigenic drift. The minor clade was paired with N2-02B.2 clade, acquired an N2-02A.2 in 2016, and we observed antigenic drift between the N2-02B.2 and -02A.2 clades. The major H3 clade paired with nucleoprotein (NP) of the H1N1pdm09 lineage rather than the North American swine lineage NP. Rather than genetic or antigenic diversity of the HA, our data suggest that antigenic diversity of the NA and acquisition of the H1N1pdm09 NP likely contributed to the emergence and transmission of new phylogenetic clades of C-IVA swine H3N2.