Investigation of cross‐regional spread and evolution of equine influenza H3N8 at US and global scales using Bayesian phylogeography based on balanced subsampling

Abstract

Equine influenza virus (EIV) is a highly contagious pathogen of equids, and a wellknown burden in global equine health. EIV H3N8 variants seasonally emerged and resulted in EIV outbreaks in the United States and worldwide. The present study evaluated the pattern of cross-regional EIV H3N8 spread and evolutionary characteristics at US and global scales using Bayesian phylogeography with balanced subsampling based on regional horse population size. A total of 297 haemagglutinin (HA) sequences of global EIV H3N8 were collected from 1963 to 2019 and subsampled to global subset (n = 67), raw US sequences (n = 100) and US subset (n = 44) datasets. Discrete trait phylogeography analysis was used to estimate the transmission history of EIV using four global and US genome datasets. The North American lineage was the major source of globally dominant EIV variants and spread to other global regions. The US EIV strains generally spread from the southern and midwestern regions to other regions. The EIV H3N8 accumulated approximately three nucleotide substitutions per year in the HA gene under heterogeneous local positive selection. Our findings will guide better decision making of target intervention strategies of EIV H3N8 infection and provide the better scheme of genomic surveillance in the United States and global equine health.

Understanding the Divergent Evolution and Epidemiology of H3N8 Influenza Viruses in Dogs and Horses

“…The overall clade structure reveals an apparent US-based continuous circulation that seeds multiple international transfers and outbreaks in different regions of the world (Figure 4). Some of these historical transfers have been reported and analyzed previously and confirmed here (18,(67)(68)(69)(70)(71). Our Bayesian demographic analysis of the FC1 HA1 data set (Figure S8) also shows that the effective population size largely mirrors the full-length genome data set, yet with more points of transition and changes in diversity, some of which are likely revealed by the increased sampling resolution (Figure S2B).…”

“…Yet we see continued FC1 infections in the United States between 2020 and 2022, and a potential inter-relatedness between US and European samples in that time, suggesting a potential return to the norm. Overall, it appears that the FC1 lineage of EIV is maintained in the horse population of the United States, and that provides viruses causing outbreaks in other regions of the world (69).…”

“…Overall, it appears that the FC1 lineage of EIV is maintained in the horse population of the United States, and that provides viruses causing outbreaks in other regions of the world (69).…”

Understanding the divergent evolution and epidemiology of H3N8 influenza viruses in dogs and horses

“…Yet, we see continued FC1 infections in the USA between 2020 and 2022, and a potential inter-relatedness between US and European samples in that time, suggesting a potential return to the norm. Overall, it appears that the FC1 lineage of EIV is maintained in the horse population of the USA, and that provides viruses causing outbreaks in other regions of the world ( Lee et al. 2022a ).…”

Equine Influenza Virus: An Old Known Enemy in the Americas

“…A prevalence of 9.3% was reported in horses with acute respiratory clinical signs in a study conducted from 2010 to 2013 [ 50 ], and recently, a rt-qPCR frequency of 6,8% was reported in a voluntary sampling of 10,296 equids with acute onset of fever and/or respiratory signs for rostral nasal secretions in the country between 2008 and 2021 [ 83 ]. Phylogenetic analyses of EIV H3N8 strains from 2012 to 2017 based on the HA gene have shown that H3N8 strains from the US underwent antigenic drift and fixed multiple substitutions accumulated in the HA gene [ 84 ] and that the H3N8 FC1 North American lineage was the major source of globally dominant EIV variants and spread to other global regions [ 85 ].…”