Emergence and adaptation of H3N2 canine influenza virus from avian influenza virus: An overlooked role of dogs in interspecies transmission

H3N2 canine influenza virus (CIV) originated from avian species and emerged in dogs in Asia around 2005 where it became enzootic before reaching the USA in 2015. To investigate the key aspects of the evolution of H3N2 CIV regarding its emergence and adaptation in the canine host, we conducted an extensive analysis of all publicly available H3N2 CIV sequences spanning a 10-year period. We believe that H3N2 AIVs transferred to canines around 2002-2004. Furthermore, H3N2 CIVs could be divided into seven major clades with strong geographic clustering and some changed sites evidence of adaptive evolution. Most notably, the dN/dS of each H3N2 CIVs segment was higher than the correspondent of H3N2 AIVs and the U content of HA and NA was increasing over time, suggesting the idea that this avian-origin virus may be gradually adapting to the host. Our results provide a framework to elucidate a general mechanism for emergence of novel influenza viruses.

[1]  E. Holmes,et al.  Multiple Incursions and Recurrent Epidemic Fade-Out of H3N2 Canine Influenza A Virus in the United States , 2018, Journal of Virology.

[2]  Alexander Mehler,et al.  TreeAnnotator: Versatile Visual Annotation of Hierarchical Text Relations , 2018, LREC.

[3]  C. Macken,et al.  Characterization of a Feline Influenza A(H7N2) Virus , 2018, Emerging infectious diseases.

[4]  E. Holmes,et al.  Spread of Canine Influenza A(H3N2) Virus, United States , 2017, Emerging infectious diseases.

[5]  C. Davis,et al.  Avian Influenza A(H7N2) Virus in Human Exposed to Sick Cats, New York, USA, 2016 , 2017, Emerging infectious diseases.

[6]  G. Gao,et al.  Epidemiology, Evolution, and Pathogenesis of H7N9 Influenza Viruses in Five Epidemic Waves since 2013 in China. , 2017, Trends in microbiology.

[7]  Guohua Yang,et al.  Zoonotic Risk, Pathogenesis, and Transmission of Avian-Origin H3N2 Canine Influenza Virus , 2017, Journal of Virology.

[8]  T. Tumpey,et al.  A Novel A(H7N2) Influenza Virus Isolated from a Veterinarian Caring for Cats in a New York City Animal Shelter Causes Mild Disease and Transmits Poorly in the Ferret Model , 2017, Journal of Virology.

[9]  E. Holmes,et al.  Comparative analysis estimates the relative frequencies of co-divergence and cross-species transmission within viral families , 2017, PLoS pathogens.

[10]  K. Ikuta,et al.  Novel Polymerase Gene Mutations for Human Adaptation in Clinical Isolates of Avian H5N1 Influenza Viruses , 2016, PLoS pathogens.

[11]  Sudhir Kumar,et al.  MEGA7: Molecular Evolutionary Genetics Analysis Version 7.0 for Bigger Datasets. , 2016, Molecular biology and evolution.

[12]  Andrew Rambaut,et al.  Exploring the temporal structure of heterochronous sequences using TempEst (formerly Path-O-Gen) , 2016, Virus evolution.

[13]  J. Hughes,et al.  Origins and Evolutionary Dynamics of H3N2 Canine Influenza Virus , 2015, Journal of Virology.

[14]  Sergei L. Kosakovsky Pond,et al.  UC Office of the President Recent Work Title Less Is More : An Adaptive Branch-Site Random Effects Model for Efficient Detection of Episodic Diversifying Selection Permalink , 2015 .

[15]  R. Webster,et al.  H3N2 canine influenza virus with the matrix gene from the pandemic A/H1N1 virus: infection dynamics in dogs and ferrets , 2014, Epidemiology and Infection.

[16]  Michael Worobey,et al.  A synchronized global sweep of the internal genes of modern avian influenza virus , 2014, Nature.

[17]  A. Amonsin,et al.  Genetic characterization of canine influenza A virus (H3N2) in Thailand , 2014, Virus Genes.

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

[19]  A. Osterhaus,et al.  Genomewide Analysis of Reassortment and Evolution of Human Influenza A(H3N2) Viruses Circulating between 1968 and 2011 , 2013, Journal of Virology.

[20]  H. Moon,et al.  A novel canine influenza H3N2 virus isolated from cats in an animal shelter. , 2013, Veterinary microbiology.

[21]  K. Subbarao,et al.  Mammalian Adaptation in the PB2 Gene of Avian H5N1 Influenza Virus , 2013, Journal of Virology.

[22]  L. Brunotte,et al.  Adaptation of Avian Influenza A Virus Polymerase in Mammals To Overcome the Host Species Barrier , 2013, Journal of Virology.

[23]  H. Poo,et al.  Complete Genome Sequence of a Canine-Origin H3N2 Feline Influenza Virus Isolated from Domestic Cats in South Korea , 2013, Genome Announcements.

[24]  Sergei L. Kosakovsky Pond,et al.  FUBAR: a fast, unconstrained bayesian approximation for inferring selection. , 2013, Molecular biology and evolution.

[25]  Sergei L. Kosakovsky Pond,et al.  Detecting Individual Sites Subject to Episodic Diversifying Selection , 2012, PLoS genetics.

[26]  Theo M Bestebroer,et al.  Airborne Transmission of Influenza A/H5N1 Virus Between Ferrets , 2012, Science.

[27]  R. Webster,et al.  A novel reassortant canine H3N1 influenza virus between pandemic H1N1 and canine H3N2 influenza viruses in Korea. , 2012, The Journal of general virology.

[28]  E. Holmes,et al.  Genome-Scale Evolution and Phylodynamics of Equine H3N8 Influenza A Virus , 2011, Journal of Virology.

[29]  P. Jiao,et al.  Avian-origin H3N2 canine influenza A viruses in Southern China. , 2010, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[30]  Sergei L. Kosakovsky Pond,et al.  Datamonkey 2010: a suite of phylogenetic analysis tools for evolutionary biology , 2010, Bioinform..

[31]  Yi Guan,et al.  Full Factorial Analysis of Mammalian and Avian Influenza Polymerase Subunits Suggests a Role of an Efficient Polymerase for Virus Adaptation , 2009, PloS one.

[32]  S. Brody,et al.  Experimental Evolution of Human Influenza Virus H3 Hemagglutinin in the Mouse Lung Identifies Adaptive Regions in HA1 and HA2 , 2009, Journal of Virology.

[33]  S. Brody,et al.  Experimental Evolution of Human Influenza Virus H3 Hemagglutinin in the Mouse Lung Identifies Adaptive Regions in HA1 and HA2 , 2008, Journal of Virology.

[34]  R. Donis,et al.  Influenza A Virus (H3N8) in Dogs with Respiratory Disease, Florida , 2008, Emerging infectious diseases.

[35]  O. Pybus,et al.  Correlating viral phenotypes with phylogeny: accounting for phylogenetic uncertainty. , 2008, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[36]  Bongkyun Park,et al.  Transmission of Avian Influenza Virus (H3N2) to Dogs , 2008, Emerging infectious diseases.

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

[38]  Raul Rabadan,et al.  Comparison of Avian and Human Influenza A Viruses Reveals a Mutational Bias on the Viral Genomes , 2006, Journal of Virology.

[39]  J. Hancock,et al.  Ethylene-induced stomatal closure in Arabidopsis occurs via AtrbohF-mediated hydrogen peroxide synthesis. , 2006, The Plant journal : for cell and molecular biology.

[40]  Yoshihiro Kawaoka,et al.  Avian flu: Influenza virus receptors in the human airway , 2006, Nature.

[41]  Calvin M. Johnson,et al.  Transmission of Equine Influenza Virus to Dogs , 2005, Science.

[42]  Y. Guan,et al.  Are Ducks Contributing to the Endemicity of Highly Pathogenic H5N1 Influenza Virus in Asia? , 2005, Journal of Virology.

[43]  Ian A. Wilson,et al.  A Single Amino Acid Substitution in 1918 Influenza Virus Hemagglutinin Changes Receptor Binding Specificity , 2005, Journal of Virology.

[44]  Sergei L. Kosakovsky Pond,et al.  Not so different after all: a comparison of methods for detecting amino acid sites under selection. , 2005, Molecular biology and evolution.

[45]  Y. Guan,et al.  Reemerging H5N1 Influenza Viruses in Hong Kong in 2002 Are Highly Pathogenic to Ducks , 2004, Journal of Virology.

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

[47]  R. Nielsen.  Statistical tests of selective neutrality in the age of genomics , 2001, Heredity.

[48]  Yoshihiro Kawaoka,et al.  Early Alterations of the Receptor-Binding Properties of H1, H2, and H3 Avian Influenza Virus Hemagglutinins after Their Introduction into Mammals , 2000, Journal of Virology.

[49]  A. Osterhaus,et al.  Characterization of adaptation of an avian influenza A (H5N2) virus to a mammalian host. , 2000, Acta virologica.

[50]  R. Webster,et al.  Interspecies transmission of influenza viruses. , 1995, American journal of respiratory and critical care medicine.

[51]  R. Webster,et al.  Receptor specificity in human, avian, and equine H2 and H3 influenza virus isolates. , 1994, Virology.

[52]  R. Webster,et al.  Genetic reassortment between avian and human influenza A viruses in Italian pigs. , 1993, Virology.

[53]  R. Webster,et al.  Evolution and ecology of influenza A viruses. , 1992, Current topics in microbiology and immunology.

[54]  Bongkyun Park,et al.  Transmission of Avian Infl uenza Virus ( H 3 N 2 ) to Dogs , 2019 .

[55]  R. Webster,et al.  H 3 N 2 canine in fl uenza virus with the matrix gene from the pandemic A / H 1 N 1 virus : infection dynamics in dogs and ferrets , 2015 .

[56]  R. Webster,et al.  A novel reassortant canine H 3 N 1 influenza virus between pandemic H 1 N 1 and canine H 3 N 2 influenza viruses in Korea , 2012 .

[57]  Kathy Hancock.  Influenza A Virus , 2020, Definitions.

[58]  T. A. Hall,et al.  BIOEDIT: A USER-FRIENDLY BIOLOGICAL SEQUENCE ALIGNMENT EDITOR AND ANALYSIS PROGRAM FOR WINDOWS 95/98/ NT , 1999 .

[59]  J. Kehoe,et al.  Demonstration of antibodies to both hemagglutinin and neuraminidase antigens of H3N2 influenza A virus in domestic dogs. , 1975, Intervirology.