Location: Virus and Prion ResearchTitle: Genetic and antigenic characterization of the expanding H3 Cluster IV-A influenza A virus clade in US swine
|NEVEAU, MEGAN - Iowa State University
|ZELLER, MICHAEL - Iowa State University
|ZOUZA, CARINE - Orise Fellow
|GAUDER, PHILLIP - Iowa State University
Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 3/29/2021
Publication Date: 4/16/2021
Citation: Neveau, M.N., Zeller, M.A., Zouza, C.K., Gauder, P.C., Vincent, A.L., Anderson, T.K. 2021. Genetic and antigenic characterization of the expanding H3 Cluster IV-A influenza A virus clade in US swine [abstract]. Annual Bioinformatics and Computational Biology Symposium. P. none assigned.
Technical Abstract: The genetic and antigenic diversity of influenza A virus (IAV) in pigs is shaped by interspecies transmission and subsequent evolution of the virus within pig populations via drift and reassortment. In 2019, a group of genetically similar H3 IAVs (1990.4.a) that has circulated in pigs for 20 years was detected to be increasing in frequency in US swine. To determine putative mechanisms associated with this increase, we conducted a comprehensive phylogenetic analysis and paired these data with a phenotypic assessment of antigenicity in representative viruses from within the clade. Phylodynamic analysis of the HA gene documented low relative genetic diversity within the recent detections, suggesting clonal expansion of genetically similar viruses. We developed and deployed an interactive web tool to track the emergence, spatial spread, and genetic evolution of H3 IAV in swine (nextstrain for swine IAV: flu-crew.org). These data identified two clades that emerged concurrently and are cocirculating within multiple US states. The clade with the majority of detections was associated with a conserved amino acid substitution at position 156; this position is one of six that have previously been associated with having a disproportionate impact on antigenic phenotype. Using a series of empirical hemagglutination inhibition assays, we quantified the phenotype of viruses with and without mutation at position 156 and demonstrated that this mutation did not result in significant antigenic drift. We also quantified diversity outside of the HA gene, by analyzing whole genome sequences from 401 isolates and neuraminidase sequences from 1087 isolates within the genetic clade. These analyses documented reassortment in both cocirculating clades: the minor clade was paired with N2-2002B in ancestral strains, but more recently with N2-2002A; in the major clade, nucleoprotein (NP) from the TRIG lineage was replaced with NP of the pandemic lineage. Our data demonstrate that the expansion of this genetic clade is not associated with an increase in relative genetic or antigenic diversity of the HA gene. The reassortment and acquisition of novel genome constellations including a new NP gene may have impacted replication and transmission. Defining the genetic and antigenic factors contributing to the expansion of IAV in swine is essential to understanding and predicting mechanisms that viruses employ to evade current control measures and reduce the chance of a swine-origin IAV emerging that has zoonotic potential.