Location: Virus and Prion ResearchTitle: N2 NA and HA coordinated evolution increases influenza A virus genetic diversity in swine
|ZELLER, MICHAEL - Iowa State University
|GAUGER, PHILLIP - Iowa State University
Submitted to: Research Workers in Animal Diseases Conference Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: 10/15/2018
Publication Date: 11/30/2018
Citation: Zeller, M.A., Anderson, T.K., Vincent, A.L., Gauger, P.C. 2018. N2 NA and HA coordinated evolution increases influenza A virus genetic diversity in swine [abstract]. Research Workers in Animal Diseases Conference Proceedings. p. none assigned.
Technical Abstract: Objectives The objective of this study was to 1) quantify the genetic diversity of N2 neuraminidase (NA) genes from swine influenza A viruses (IAV), and 2) determine if there is coordinated evolution between the NA and hemagglutinin (HA) surface proteins. Methods N2 genes were collated from all publicly available swine IAV NA sequences from 2009 to present. Each gene was assigned to one of two major lineages, N2.1998 or N2.2002, derived from separate human-to-swine introduction events in the late 1990s and early 2000s respectively. Demographic modeling with BEAST 1.8.4 was used to estimate the effective population size of the N2.2002 and N2.1998 clades. The pairing between HA and NA genes was statistically assessed (Pearson's chi-squared test), and reassortment was quantified using tanglegrams and entanglement metrics. Results From 2009 to present, there was a linear increase in the relative genetic diversity of the N2.2002 clade. The N2.1998 data demonstrated a rapid increase in diversity in 2014, followed by a sharp decline in 2017. There was non-random pairing between phylogenetic clades of HA and NA sequences (Chi-squared: p < 0.0001). Topologies of HA and NA gene trees indicated clade specific reassortment of the N2 occurred between different HA clades. The entanglement index for the HA-NA tanglegram was 0.29, suggesting non-random pairing of genes from specific phylogenetic clades. Conclusions Following the 2009 pandemic, reassortment and an increase in the NA N2 genetic diversity was observed. We demonstrate a correlation between reassortment of HA and NA and relative genetic diversity in the NA gene. In addition, we document non-random pairing between HA and NA genes. These data suggest that the observed diversification of swine IAV is the result of an interplay between genetic drift and clade-specific reassortment. The frequency of reassortment of N2 may be due to selective pressure to optimize function as well as co-evolution of HA and NA pairing. The increased reassortment and evolution of NA, and resultant evolution of the HA, likely affects viral phenotype and drives antigenic drift.