Emergence and Evolution of Novel Reassortant Influenza A Viruses in Canines in Southern China.

Ying Chen1,2,3 Nídia S Trovão2,3,4 Guojun Wang2,3 Weifeng Zhao1 Ping He1 Huabo Zhou1,5 Yanning Mo1 Zuzhang Wei1 Kang Ouyang1 Weijian Huang1 Adolfo García-Sastre3,6,7 Martha I Nelson4
Affiliations 7 institutions
  1. College of Animal Science and Technology, Guangxi University, Nanning, Guangxi, China.
  2. Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  3. Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  4. Division of International Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, Bethesda, Maryland, USA.
  5. Huabo Pet Hospital, Nanning, Guangxi, China.
  6. Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA [email protected].
  7. Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Abstract

The capacity of influenza A viruses (IAVs) to host jump from animal reservoir species to humans presents an ongoing pandemic threat. Birds and swine are considered major reservoirs of viral genetic diversity, whereas equines and canines have historically been restricted to one or two stable IAV lineages with no transmission to humans. Here, by sequencing the complete genomes of 16 IAVs obtained from canines in southern China (Guangxi Zhuang Autonomous Region [Guangxi]) in 2013 to 2015, we demonstrate that the evolution of canine influenza viruses (CIVs) in Asian dogs is increasingly complex, presenting a potential threat to humans. First, two reassortant H1N1 virus genotypes were introduced independently from swine into canines in Guangxi, including one genotype associated with a zoonotic infection. The genomes contain segments from three lineages that circulate in swine in China: North American triple reassortant H3N2, Eurasian avian-like H1N1, and pandemic H1N1. Furthermore, the swine-origin H1N1 viruses have transmitted onward in canines and reassorted with the CIV-H3N2 viruses that circulate endemically in Asian dogs, producing three novel reassortant CIV genotypes (H1N1r, H1N2r, and H3N2r [r stands for reassortant]). CIVs from this study were collected primarily from pet dogs presenting with respiratory symptoms at veterinary clinics, but dogs in Guangxi are also raised for meat, and street dogs roam freely, creating a more complex ecosystem for CIV transmission. Further surveillance is greatly needed to understand the full genetic diversity of CIV in southern China, the nature of viral emergence and persistence in the region's diverse canine populations, and the zoonotic risk as the viruses continue to evolve.IMPORTANCE Mammals have emerged as critically underrecognized sources of influenza virus diversity, including pigs that were the source of the 2009 pandemic and bats and bovines that harbor highly divergent viral lineages. Here, we identify two reassortant IAVs that recently host switched from swine to canines in southern China, including one virus with known zoonotic potential. Three additional genotypes were generated via reassortment events in canine hosts, demonstrating the capacity of dogs to serve as "mixing vessels." The continued expansion of IAV diversity in canines with high human contact rates requires enhanced surveillance and ongoing evaluation of emerging pandemic threats.

Supporting text Virus Host Location
canine 10 influenza 61 virus emergence 1 virus evolution 21 Evolution, Molecular 176 Animals 1948 Cattle 126 Cattle Diseases 47 China 229 Communicable Diseases, Emerging 33 Dog Diseases 65 Dogs 176 Genetic Variation 127 Humans 1440 Influenza A Virus, H1N1 Subtype 74 Influenza A Virus, H3N2 Subtype 48 Influenza, Human 286 Orthomyxoviridae Infections 228 Phylogeny 805 Reassortant Viruses 103 Swine 258 Swine Diseases 153 Zoonoses 397

Evidence records

4 total
Zoonotic Surveillance
1 records · 1 evidence types
Evidence type
1 records
OVE3008
Key finding

Influenza A viruses were detected and their complete genomes sequenced from 16 canines sampled in Guangxi, southern China between 2013 and 2015.

Virus
Host
Location
Supporting text

By sequencing the complete genomes of 16 IAVs obtained from canines in southern China (Guangxi Zhuang Autonomous Region [Guangxi]) in 2013 to 2015, we demonstrate that the evolution of canine influenza viruses (CIVs) in Asian dogs is increasingly complex.

Method
complete genome sequencing
Sample type
respiratory samples | canine specimens
Geographic raw
southern China | Guangxi Zhuang Autonomous Region
Country inferred
CHN
Genomic Evolution
3 records · 2 evidence types
Evidence type
2 records
OVE3010
Key finding

Swine-origin H1N1 viruses reassorted with endemic canine influenza virus H3N2 in Asian dogs, generating three novel reassortant genotypes H1N1r, H1N2r, and H3N2r.

Virus
Host
Not specified
Location
Not specified
Supporting text

The swine-origin H1N1 viruses have transmitted onward in canines and reassorted with the CIV-H3N2 viruses that circulate endemically in Asian dogs, producing three novel reassortant CIV genotypes (H1N1r, H1N2r, and H3N2r).

Event type
reassortment
OVE3009
Key finding

Two reassortant H1N1 virus genotypes were transmitted independently from swine to canines in Guangxi, indicating cross-species transmission between pigs and dogs.

Virus
Host
Location
Supporting text

Two reassortant H1N1 virus genotypes were introduced independently from swine into canines in Guangxi, including one genotype associated with a zoonotic infection.

Event type
reassortment
Evidence type
1 records
OVE3012
Key finding

Phylogenetic analysis showed that canine influenza virus genomes contained gene segments derived from three swine influenza lineages—North American triple reassortant H3N2, Eurasian avian-like H1N1, and pandemic H1N1—indicating a multi-lineage evolutionary origin of the canine strains.

Virus
Host
Location
Not specified
Supporting text

The genomes contain segments from three lineages that circulate in swine in China: North American triple reassortant H3N2, Eurasian avian-like H1N1, and pandemic H1N1.

Analysis methods
phylogenetic analysis | genomic comparison