The genomic evolution of H1 influenza A viruses from swine detected in the United States between 2009 and 2016.

Transmission of influenza A virus (IAV) from humans to swine occurs with relative frequency and is a critical contributor to swine IAV diversity. Subsequent to the introduction of these human seasonal lineages, there is often reassortment with endemic viruses and antigenic drift. To address whether particular genome constellations contributed to viral persistence following the introduction of the 2009 H1N1 human pandemic virus to swine in the USA, we collated and analysed 616 whole genomes of swine H1 isolates. For each gene, sequences were aligned, the best-known maximum likelihood phylogeny was inferred, and each virus was assigned a clade based upon its evolutionary history. A time-scaled Bayesian approach was implemented for the haemagglutinin (HA) gene to determine the patterns of genetic diversity over time. From these analyses, we observed an increase in genome diversity across all H1 lineages and clades, with the H1-γ and H1-δ1 genetic clades containing the greatest number of unique genome patterns. We documented 74 genome patterns from 2009 to 2016, of which 3 genome patterns were consistently detected at a significantly higher level than others across the entire time period. Eight genome patterns increased significantly, while five genome patterns were shown to decline in detection over time. Viruses with genome patterns identified as persisting in the US swine population may possess a greater capacity to infect and transmit in swine. This study highlights the emerging genetic diversity of US swine IAV from 2009 to 2016, with implications for swine and public health and vaccine control efforts.

[1]  S. Detmer,et al.  Vaccination of influenza a virus decreases transmission rates in pigs , 2011, Veterinary research.

[2]  A. Vincent,et al.  Continual Reintroduction of Human Pandemic H1N1 Influenza A Viruses into Swine in the United States, 2009 to 2014 , 2015, Journal of Virology.

[3]  S. Ho,et al.  Relaxed Phylogenetics and Dating with Confidence , 2006, PLoS biology.

[4]  Tavis K. Anderson,et al.  Characterization of co-circulating swine influenza A viruses in North America and the identification of a novel H1 genetic clade with antigenic significance. , 2015, Virus research.

[5]  R. Kahn,et al.  The pig as a mixing vessel for influenza viruses: Human and veterinary implications , 2008, Journal of molecular and genetic medicine : an international journal of biomedical research.

[6]  A. Ishihama,et al.  Influenza virus PB1 protein is the minimal and essential subunit of RNA polymerase , 2005, Archives of Virology.

[7]  S. Detmer,et al.  The impact of maternally derived immunity on influenza A virus transmission in neonatal pig populations. , 2013, Vaccine.

[8]  T. Tatusova,et al.  The Influenza Virus Resource at the National Center for Biotechnology Information , 2007, Journal of Virology.

[9]  Mariette F. Ducatez,et al.  Multiple reassortment between pandemic (H1N1) 2009 and endemic influenza viruses in pigs, United States. , 2011, Emerging infectious diseases.

[10]  O. Pybus,et al.  Bayesian coalescent inference of past population dynamics from molecular sequences. , 2005, Molecular biology and evolution.

[11]  G. Serio,et al.  A new method for calculating evolutionary substitution rates , 2005, Journal of Molecular Evolution.

[12]  I. Wilson,et al.  Functional Balance of the Hemagglutinin and Neuraminidase Activities Accompanies the Emergence of the 2009 H1N1 Influenza Pandemic , 2012, Journal of Virology.

[13]  C. Viboud,et al.  Introductions and Evolution of Human-Origin Seasonal Influenza A Viruses in Multinational Swine Populations , 2014, Journal of Virology.

[14]  Sagar M. Goyal,et al.  Evolution of Swine H3N2 Influenza Viruses in the United States , 2000, Journal of Virology.

[15]  Gavin J. D. Smith,et al.  Reassortment of Pandemic H1N1/2009 Influenza A Virus in Swine , 2010, Science.

[16]  Alexandros Stamatakis,et al.  RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies , 2014, Bioinform..

[17]  A. Bowman,et al.  Exploration of risk factors contributing to the presence of influenza A virus in swine at agricultural fairs , 2014, Emerging Microbes & Infections.

[18]  R. Webby,et al.  Influenza Virus Surveillance in Coordinated Swine Production Systems, United States , 2015, Emerging infectious diseases.

[19]  Wolfgang Schramm,et al.  Team , 2018, Spaces of Intensity.

[20]  Martin Hartmann,et al.  Introducing mothur: Open-Source, Platform-Independent, Community-Supported Software for Describing and Comparing Microbial Communities , 2009, Applied and Environmental Microbiology.

[21]  T. Lam,et al.  Molecular Epidemiology and Evolution of Influenza Viruses Circulating within European Swine between 2009 and 2013 , 2015, Journal of Virology.

[22]  M. Nelson,et al.  Evolutionary Dynamics of Influenza A Viruses in US Exhibition Swine. , 2016, The Journal of infectious diseases.

[23]  Amy L. Vincent,et al.  Evolution of Novel Reassortant A/H3N2 Influenza Viruses in North American Swine and Humans, 2009–2011 , 2012, Journal of Virology.

[24]  A. Rambaut,et al.  BEAST: Bayesian evolutionary analysis by sampling trees , 2007, BMC Evolutionary Biology.

[25]  Tavis K. Anderson,et al.  Novel Reassortant Human-Like H3N2 and H3N1 Influenza A Viruses Detected in Pigs Are Virulent and Antigenically Distinct from Swine Viruses Endemic to the United States , 2015, Journal of Virology.

[26]  David K. Smith,et al.  Expansion of Genotypic Diversity and Establishment of 2009 H1N1 Pandemic-Origin Internal Genes in Pigs in China , 2014, Journal of Virology.

[27]  R. Webby,et al.  Active Surveillance for Influenza A Virus among Swine, Midwestern United States, 2009–2011 , 2013, Emerging infectious diseases.

[28]  Genotype patterns of contemporary reassorted H3N2 virus in US swine. , 2013 .

[29]  A. Bowman,et al.  Prevalence of Influenza A Virus in Exhibition Swine during Arrival at Agricultural Fairs , 2016, Zoonoses and public health.

[30]  Amy L. Vincent,et al.  Reassortment between Swine H3N2 and 2009 Pandemic H1N1 in the United States Resulted in Influenza A Viruses with Diverse Genetic Constellations with Variable Virulence in Pigs , 2016, Journal of Virology.

[31]  Cécile Viboud,et al.  Spatial Dynamics of Human-Origin H1 Influenza A Virus in North American Swine , 2011, PLoS pathogens.

[32]  Gavin J. D. Smith,et al.  Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic , 2009, Nature.

[33]  A. Vincent,et al.  Characterization of a newly emerged genetic cluster of H1N1 and H1N2 swine influenza virus in the United States , 2009, Virus Genes.

[34]  Gavin J. D. Smith,et al.  Long-term evolution and transmission dynamics of swine influenza A virus , 2011, Nature.

[35]  Tavis K. Anderson,et al.  A Phylogeny-Based Global Nomenclature System and Automated Annotation Tool for H1 Hemagglutinin Genes from Swine Influenza A Viruses , 2016, mSphere.

[36]  C. Scholtissek,et al.  Pigs as ‘Mixing Vessels’ for the Creation of New Pandemic Influenza A Viruses , 1990 .

[37]  S. Sreevatsan,et al.  Swine-to-Human Transmission of Influenza A(H3N2) Virus at Agricultural Fairs, Ohio, USA, 2012 , 2014, Emerging infectious diseases.

[38]  Tavis K. Anderson,et al.  Population dynamics of cocirculating swine influenza A viruses in the United States from 2009 to 2012 , 2013, Influenza and other respiratory viruses.

[39]  Ron A M Fouchier,et al.  Antigenic and Genetic Characteristics of Swine-Origin 2009 A(H1N1) Influenza Viruses Circulating in Humans , 2009, Science.

[40]  Mark A. Miller,et al.  Creating the CIPRES Science Gateway for inference of large phylogenetic trees , 2010, 2010 Gateway Computing Environments Workshop (GCE).

[41]  T. Stockwell,et al.  Genomic reassortment of influenza A virus in North American swine, 1998-2011. , 2012, The Journal of general virology.

[42]  H. Goto,et al.  Identification of a Novel Viral Protein Expressed from the PB2 Segment of Influenza A Virus , 2015, Journal of Virology.

[43]  G. Simon,et al.  Dynamics of influenza A virus infections in permanently infected pig farms: evidence of recurrent infections, circulation of several swine influenza viruses and reassortment events , 2013, Veterinary Research.

[44]  Robert C. Edgar,et al.  MUSCLE: multiple sequence alignment with high accuracy and high throughput. , 2004, Nucleic acids research.

[45]  S. Holm A Simple Sequentially Rejective Multiple Test Procedure , 1979 .

[46]  Alexandros Stamatakis,et al.  How Many Bootstrap Replicates Are Necessary? , 2009, RECOMB.

[47]  R. Webster,et al.  Genetic Reassortment of Avian, Swine, and Human Influenza A Viruses in American Pigs , 1999, Journal of Virology.

[48]  Tavis K. Anderson,et al.  Pathogenesis and vaccination of influenza A virus in swine. , 2014, Current topics in microbiology and immunology.

[49]  Daniel L. Ayres,et al.  BEAGLE: An Application Programming Interface and High-Performance Computing Library for Statistical Phylogenetics , 2011, Systematic biology.