Equine Influenza Virus in Asia: Phylogeographic Pattern and Molecular Features Reveal Circulation of an Autochthonous Lineage

Abstract

Equine influenza virus (EIV) causes severe acute respiratory disease in horses. Currently, the strains belonging to the H3N8 subtype are divided into two clades, Florida clade 1 (FC1) and Florida clade 2 (FC2), which emerged in 2002. Both FC1 and FC2 clades were reported in Asian and Middle East countries in the last decade. In this study, we described the evolution, epidemiology, and molecular characteristic of the EIV lineages, with focus on those detected in Asia from 2007 to 2017. The full genome phylogeny showed that FC1 and FC2 constituted separate and divergent lineages, without evidence of reassortment between the clades. While FC1 evolved as a single lineage, FC2 showed a divergent event around 2004 giving rise to two well-supported and coexisting sublineages, European and Asian. Furthermore, two different spread patterns of EIV in Asian countries were identified. The FC1 outbreaks were caused by independent introductions of EIV from the Americas, with the Asian isolates genetically similar to the contemporary American lineages. On the other hand, the FC2 strains detected in Asian mainland countries conformed to an autochthonous monophyletic group with a common ancestor dated in 2006 and showed evidence of an endemic circulation in a local host. Characteristic aminoacidic signature patterns were detected in all viral proteins in both Asian-FC1 and FC2 populations. Several changes were located at the top of the HA1 protein, inside or near antigenic sites. Further studies are needed to assess the potential impact of these antigenic changes in vaccination programs. IMPORTANCE The complex and continuous antigenic evolution of equine influenza viruses (EIVs) remains a major hurdle for vaccine development and the design of effective immunization programs. The present study provides a comprehensive analysis showing the EIV evolutionary dynamics, including the spread and circulation within the Asian continent and its relationship to global EIV populations over a 10-year period. Moreover, we provide a better understanding of EIV molecular evolution in Asian countries and its consequences on the antigenicity. The study underscores the association between the global horse movement and the circulation of EIV in this region. Understanding EIV evolution is imperative in order to mitigate the risk of outbreaks affecting the horse industry and to help with the selection of the viral strains to be included in the formulation of future vaccines.

Long-term adaptation following influenza A virus host shifts results in increased within-host viral fitness due to higher replication rates, broader dissemination within the respiratory epithelium and reduced tissue damage

“…This is illustrated by the large number of amino acid changes observed in the main trunk of the phylogenies of each viral genomic segment [ 27 ]. Further, some of those mutations showed evidence of positive selection as well as adaptive evolution [ 18 , 27 ], consistent with the notion that virus adaptation is polygenic. Experimental approaches identified the effect of individual mutations on H3N8 EIV antigenicity: mutations in the haemagglutinin (HA) gene led to immune escape from vaccine strains via antigenic drift [ 28 ], which in turn increased the probability of EIV transmission [ 29 ].…”

“…H3N8 equine influenza virus (EIV) is the only subtype currently circulating amongst equine populations, as other avian-origin EIVs such as the H7N7 subtype became extinct. H3N8 EIV was first reported in USA in 1963 [15] during an outbreak of highly transmissible respiratory disease that led to a panzootic and the establishment of EIV as an endemic lineage in several countries [18][19][20][21]. Equine influenza is characterised by lesions predominantly in the upper and middle respiratory tract, such as rhinitis and tracheitis, where virus antigen is often detected [22].…”

Immunogenicity of Calvenza-03 EIV/EHV® Vaccine in Horses: Comparative In Vivo Study

“…EI is extremely contagious and causes up to 100% morbidity; however, it is fatal in very young animals and immunocompromised old horses. Recently, continuous EI outbreaks have been reported in several countries, including USA, Europe, Asia, and African countries [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. EI is caused by an orthomyxovirus of the genus influenza A virus that can undergo antigenic drift and shift to escape host immune defenses.…”

Global Spread of the B5 Subgenotype EV-A71 and the Phylogeographical Analysis of Chinese Migration Events

“…Phylogeographic analysis is used to track migration and make predictions. Previously, it has been widely used for diseases like rabies, influenza, and yellow fever (Beck et al, 2013 ; Dellicour et al, 2019 ; Mino et al, 2019 ). The current study attempted to illustrate the state of spread of the B5 subgenotype of EV-A71.…”