Host Adaptive Evolution of Avian-Origin H3N2 Canine Influenza Virus.

Fucheng Guo,Zhipeng Zhang,Ruichen Wang,David M Irwin,Rui-Ai Chen,Ayan Roy,Yongyi Shen,Wen Luo,Jinjin Yang,Xuejuan Shen

doi:10.3389/fmicb.2021.655228

Abstract

Since its first isolation in around 2007, the avian-origin H3N2 canine influenza virus (CIV) has become established and continues to circulate in dog populations. This virus serves as a useful model for deciphering the complex evolutionary process of interspecies transmission of influenza A virus (IAV) from one species to its subsequent circulation in another mammalian host. The present investigation is a comprehensive effort to identify and characterize genetic changes that accumulated in the avian-origin H3N2 CIV during its circulation in the dog. We revealed that H3N2 CIV experiences greater selection pressure with extremely high global non-synonymous to synonymous substitution ratios per codon (dN/dS ratio) for each gene compared to the avian reservoir viruses. A total of 54 amino acid substitutions were observed to have accumulated and become fixed in the H3N2 CIV population based on our comprehensive codon-based frequency diagram analysis. Of these substitutions, 11 sites also display high prevalence in H3N8 CIV, indicating that convergent evolution has occurred on different lineages of CIV. Notably, six substitutions, including HA-G146S, M1-V15I, NS1-E227K, PA-C241Y, PB2-K251R, and PB2-G590S, have been reported to play imperative roles in facilitating the transmission and spillover of IAVs across species barriers. Most of these substitutions were found to have become fixed in around 2015, which might have been a favorable factor that facilitating the spread of these CIV lineages from South Asia to North America and subsequent further circulation in these areas. We also detected 12 sites in six viral genes with evidence for positive selection by comparing the rates of non-synonymous and synonymous substitutions at each site. Besides, our study reports trends of enhanced ongoing adaptation of H3N2 CIV to their respective host cellular systems, based on the codon adaptation index analysis, which points toward increasing fitness for efficient viral replication. In addition, a reduction in the abundance of the CpG motif, as evident from an analysis of relative dinucleotide abundance, may contribute to the successful evasion of host immune recognition. The present study provides key insights into the adaptive changes that have accumulated in the avian-origin H3N2 viral genomes during its establishment and circulation into dog populations.

Highlights

Influenza A virus (IAV) belongs to the family Orthomyxoviridae
This study explores and characterizes the host evolution process of H3N2 canine influenza virus (CIV) over its epidemiological time, after its interspecific transmission event from an avian IAV source and aims to unravel the riddles of the emergence and subsequent adaptation of an IAV in a new host environment
Supported by previous reports (Voorhees et al, 2018; He et al, 2019), our analysis revealed that with its establishment in canine populations, H3N2 CIV experiences greater levels of selection pressure than H3N2 avian-origin H3N2 influenza virus (AIV) or H3N8 CIV, as evident from the significantly higher dN/dS substitution ratios seen for each gene (Figure 1)

Summary

Introduction

Influenza A virus (IAV) belongs to the family Orthomyxoviridae. According to the antigenicity of surface glycoproteins, namely, hemagglutinin (HA) and neuraminidase (NA), IAVs can be subtyped into multiple HxNy subtypes, including 18 HA (H1– H18) and 11 NA (N1–N11) (Mostafa et al, 2018). H3N8 CIV circulated continuously among dogs in the United States until 2016 (Borland et al, 2020) and caused sporadic outbreaks in the dogs in the United Kingdom and Australia (Daly et al, 2008; Kirkland et al, 2010). Another CIV in canine, H3N2 CIV, was isolated from dogs around 2007 and rapidly spread into several areas of Southeast Asia (Li et al, 2010; Bunpapong et al, 2014). H3N2 CIV has successfully colonized to become an enzootic virus throughout South-East Asia and North America and occasionally causes epizootics in pet and sheltered dogs (He et al, 2019; Supplementary Figure 1)

Methods

Results

Conclusion