Skip to main content
ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Virus and Prion Research » Research » Publications at this Location » Publication #400059

Research Project: Intervention Strategies to Control Endemic and New and Emerging Influenza A Virus Infections in Swine

Location: Virus and Prion Research

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

item HUFNAGEL, DAVID - Oak Ridge Institute For Science And Education (ORISE)
item Young, Katherine
item ARENDSEE, ZEBULUN - Oak Ridge Institute For Science And Education (ORISE)
item GAY, L - University Of Georgia
item CACERES, C - University Of Georgia
item RAJAO, DANIELA - University Of Georgia
item PEREZ, DANIEL - University Of Georgia
item Baker, Amy
item Anderson, Tavis

Submitted to: Virus Evolution
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/22/2023
Publication Date: 2/28/2023
Citation: Hufnagel, D.E., Young, K.M., Arendsee, Z., Gay, L.C., Caceres, C.J., Rajao, D., Perez, D.R., Baker, A.L., Anderson, T.K. 2023. Characterizing a century of genetic diversity and contemporary antigenic diversity of N1 neuraminidase in influenza A virus from North American swine. Virus Evolution. 9(1). Article 10.1093.

Interpretive Summary: Influenza A virus (IAV) is a common pathogen in swine and leads to significant production losses every year. There is significant diversity within the H1N1 subtype and the N1 neuraminidase (NA) gene in swine is uncharacterized. Measuring genetic diversity within the N1 gene can help identify mechanisms driving IAV spread and evolution within and between hosts. Between 1930 and 2020, we described fourteen N1 groups across two evolutionary lineages, with seven groups having evidence for contemporary circulation. We tested representative swine N1 proteins and quantified differences in immune response to the different viruses. Each of the swine N1 clades was unique, and the size of the difference was linked to the genetic distance between the viruses. N1 groups and N1 pairings with the hemagglutinin (HA) surface protein gene increased and decreased in detection frequency across North America. In rare cases, when N1 genes acquired a new HA protein through reassortment, new N1 genetic groups would emerge. Our study described N1 IAV clades in swine and demonstrated how HA-NA reassortment affected the genetic and antigenic diversity of N1. These data allow us to identify emerging and dominant N1 groups and understand how genetic diversity drives the antigenic diversity of IAV in swine to improve vaccine control efforts.

Technical Abstract: Influenza A viruses (IAV) of the H1N1 classical swine lineage became endemic in North American swine following the 1918 pandemic. Additional human-to-swine transmission events after 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 swine lineage. To determine mechanisms affecting reassortment and evolution, we conducted a phylogenetic analysis of N1 and paired HA swine IAV genes in North America between 1930 and 2020. We described fourteen N1 clades within the N1 Eurasian avian lineage (including the N1 pandemic clade) and the N1 classical swine lineage. Seven N1 genetic clades had evidence for contemporary circulation. 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. Within the N1 lineage, antigenic similarity was variable and reflected shared evolutionary history. Sustained circulation and evolution of N1 genes in swine had resulted in significant antigenic distance between the N1 pandemic clade and classical swine lineage. We also observed a significant increase in the rate of evolution in the N1 pandemic clade relative to the classical lineage. Between 2010 and 2020, N1 clades and N1-HA pairings fluctuated in detection frequency across North America, with hotspots of diversity generally appearing and disappearing within two years. We also identified frequent N1-HA reassortment events (n = 36), which were rarely sustained (n = 6) and sometimes also concomitant with the emergence of new N1 genetic clades (n = 3). These data form a baseline from which we can identify N1 clades that expand in range or genetic diversity that may impact viral phenotypes or vaccine immunity and subsequently the health of North American swine.