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Coordinated evolution between N2 neuraminidase and H1 and H3 hemagglutinin genes increased influenza A virus genetic diversity in swine

Michael A. Zeller, View ORCID ProfileJennifer Chang, View ORCID ProfileAmy L. Vincent, View ORCID ProfilePhillip C. Gauger, View ORCID ProfileTavis K. Anderson
doi: https://doi.org/10.1101/2020.05.29.123828
Michael A. Zeller
aDepartment of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA
bBioinformatics and Computational Biology Program, Iowa State University, Ames, Iowa, USA
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Jennifer Chang
cVirus and Prion Research Unit, National Animal Disease Center, USDA-ARS, Ames, Iowa, USA
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Amy L. Vincent
cVirus and Prion Research Unit, National Animal Disease Center, USDA-ARS, Ames, Iowa, USA
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Phillip C. Gauger
aDepartment of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA
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Tavis K. Anderson
cVirus and Prion Research Unit, National Animal Disease Center, USDA-ARS, Ames, Iowa, USA
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  • For correspondence: tavis.anderson@usda.gov
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Abstract

The neuraminidase (NA) and hemagglutinin (HA) of influenza A virus (IAV) are essential surface glycoproteins. In this study, the evolution of subtype N2 NA paired with H1 and H3 subtype HA in swine was evaluated to understand if genetic diversity of HA and NA were linked. Using time-scaled Bayesian phylodynamic analyses, the relationships of paired swine N2 with H1 or H3 from 2009 to 2018 were evaluated. These data demonstrated increased relative genetic diversity within the major N2 clades circulating in swine (N2.1998 between 2014-2017 and N2.2002 between 2010-2016). Relative genetic diversity of NA-HA pairs (e.g., N2.1998B/ H1.Delta1B) were correlated, suggesting intergene epistasis. Preferential pairing was observed among specific NA and HA genetic clades and this was associated with gene reassortment between cocirculating influenza A strains. Using the phylogenetic topology of inferred N2 trees, the expansion of genetic diversity in the NA gene was quantified and increases in diversity were observed subsequent to NA-HA reassortment events. The rate of evolution among NA-N2 clades and HA-H1 and HA-H3 clades were similar. The frequent regional movement of pigs and their influenza viruses is a possible explanation driving this pattern of drift, reassortment, and rapid evolution. Bayesian phylodynamic analyses demonstrated strong spatial patterns in N2 genetic diversity, and that frequent interstate movement of N2 clades homogenized diversity. The reassortment and evolution of NA and its influence on HA evolution may affect antigenic drift, impacting vaccine control programs and animal health.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://github.com/flu-crew/n2-diversity

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 31, 2020.
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Coordinated evolution between N2 neuraminidase and H1 and H3 hemagglutinin genes increased influenza A virus genetic diversity in swine
Michael A. Zeller, Jennifer Chang, Amy L. Vincent, Phillip C. Gauger, Tavis K. Anderson
bioRxiv 2020.05.29.123828; doi: https://doi.org/10.1101/2020.05.29.123828
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Coordinated evolution between N2 neuraminidase and H1 and H3 hemagglutinin genes increased influenza A virus genetic diversity in swine
Michael A. Zeller, Jennifer Chang, Amy L. Vincent, Phillip C. Gauger, Tavis K. Anderson
bioRxiv 2020.05.29.123828; doi: https://doi.org/10.1101/2020.05.29.123828

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