Characterizing a century of genetic and antigenic diversity of N1 neuraminidase in influenza A virus from North American swine

Authors: DAVID, HUFNAGEL - Oak Ridge Institute For Science And Education (ORISE); Young, Katharine; ARENDSEE, ZEBULUN - Oak Ridge Institute For Science And Education (ORISE); GAY, CLAIRE - University Of Georgia; CACERES, JOAQUIN - University Of Georgia; RAJAO, DANIELA - University Of Georgia; PEREZ, DANIEL - University Of Georgia; Baker, Amy; Anderson, Tavis

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 7/7/2022
Publication Date: 8/9/2022
Citation: David, H.E., Young, K.M., Arendsee, Z.W., Gay, C.L., Caceres, J.C., Rajao, D.S., Perez, D.R., Baker, A.L., Anderson, T.K. 2022. Characterizing a century of genetic and antigenic diversity of N1 neuraminidase in influenza A virus from North American swine (abstract). Centers of Excellence for Influenza Research and Response (CEIRR) annual meeting. p. 144.

Interpretive Summary:

Technical Abstract: H1N1 classical swine lineage influenza A viruses (IAV) became endemic in North American swine following the 1918 pandemic. Additional human-to-swine transmission events subsequent to 1918, and a spillover of H1 viruses from wild birds in Europe, potentiated a rapid increase in genomic diversity via reassortment between introductions and the endemic classical lineage swine H1N1. To determine mechanisms affecting reassortment and evolution, we conducted a phylogenetic analysis of N1 and paired HA swine IAV genes between 1930 and 2020. We described fourteen N1 clades within the N1 Eurasian avian lineage (N1.E, including the N1 pandemic clade, N1.P) and the N1 classical swine lineage (N1.C). Seven N1 genetic clades had evidence for contemporary circulation. Between 2010 and 2020, N1 clades and N1-HA pairings increased and decreased in detection frequency across North America, with the diversity patterns generally turning over within two years. This was associated with frequent N1-HA reassortment events (n = 36), rarely sustained (n = 6) and concomitant with the emergence of new N1 genetic clades (n = 3). To assess antigenic drift associated with N1 genetic diversity, we generated a panel of representative swine N1 antisera and quantified the antigenic distance between wild-type viruses using enzyme-linked lectin assays and antigenic cartography. Each of the swine N1 clades was antigenically distinct, and sustained circulation and evolution resulted in significant antigenic drift between the N1.P and N1.C lineages. Although within lineage antigenic diversity was observed, the magnitude of antigenic drift did not consistently correlate with the observed genetic clades. These data form a baseline from which we can identify N1 clades that may be expanding in range or genetic diversity, that may be associated with antigenically advanced phenotypes that could impact the health of North American swine, and help identify swine IAV that represent a zoonotic threat.