High pathogenic avian influenza A(H5) viruses of clade 2.3.4.4b in Europe—Why trends of virus evolution are more difficult to predict

Abstract

Since 2016, A(H5Nx) high pathogenic avian influenza (HPAI) virus of clade 2.3.4.4b has become one of the most serious global threats not only to wild and domestic birds, but also to public health. In recent years, important changes in the ecology, epidemiology and evolution of this virus have been reported, with an unprecedented global diffusion and variety of affected birds and mammalian species. After the two consecutive and devastating epidemic waves in Europe in 2020-2021 and 2021-2022, with the second one recognized as one of the largest epidemics recorded so far, this clade has begun to circulate endemically in European wild bird populations. This study used the complete genomes of 1,956 European HPAI A(H5Nx) viruses to investigate the virus evolution during this varying epidemiological outline. We investigated the spatiotemporal patterns of A(H5Nx) virus diffusion to/from and within Europe during the 2020-2021 and 2021-2022 epidemic waves, providing evidence of ongoing changes in transmission dynamics and disease epidemiology. We demonstrated the high genetic diversity of the circulating viruses, which have undergone frequent reassortment events, providing for the first time a complete overview and a proposed nomenclature of the multiple genotypes circulating in Europe in 2020-2022. We described the emergence of a new genotype with gull adapted genes, which offered the virus the opportunity to occupy new ecological niches, driving the disease endemicity in the European wild bird population. The high propensity of the virus for reassortment, its jumps to a progressively wider number of host species, including mammals, and the rapid acquisition of adaptive mutations make the trend of virus evolution and spread difficult to predict in this unfailing evolving scenario.

Highly pathogenic avian influenza A(H5N1) virus infections on fur farms connected to mass mortalities of black-headed gulls, Finland, July to October 2023

“…The causative agent in the wild birds and the fur animals was confirmed as clade 2.3.4.4b. Phylogenetic analyses of the eight gene segments revealed that the viruses identified from all the fur animal samples and from 45 wild bird samples belonged to genotype EA-2022-BB, A/Herring_gull/France/22P015977/2022-like [ 13 ] and clustered together with A(H5N1) viruses of the same genotype that had circulated in Europe 2022–2023. The A(H5N1) viruses collected from wild birds of the EA-2022-BB genotype form three well-supported clusters (Finland-I, Finland-II and Finland-III), presented in Supplementary File 1 .…”

“…Maximum likelihood (ML) phylogenetic trees were obtained for each gene using IQTREE v1.6.6, performing ultrafast bootstrap resampling analysis (1,000 replications) and using the bestfitted nucleotide (nt) substitution model selected by ModelFinder [10][11][12]. Genotype assignment was based on the phylogenetic tree topology [13].…”

“…Evolutionary and discrete phylogeographic analyses of the concatenated genome of the HPAI A(H5N1) viruses, based on the date of sampling, were performed using BEAST v1.10.4 in combination with the BEAGLE library [15]. The dataset consists of 156 non-reassortant viruses of the EA-2022-BB (H5N1-A/Herring_gull/ France/22P015977/2022-like) [13] genotype: 19 viruses from Europe, highly related to the viruses collected in Finland, 41 viruses collected from wild birds and 96 viruses collected from 24 fur farms in Finland. The dataset was analysed using the uncorrelated lognormal relaxed molecular clock, the SRD06 substitution model [16] and a coalescent constant population size model as tree prior [17][18][19].…”

“…3.4.4b. Phylogenetic analyses of the eight gene segments revealed that the viruses identified from all the fur animal samples and from 45 wild bird samples belonged to genotype EA-2022-BB, A/Herring_gull/France/22P015977/2022like[13] and clustered together with A(H5N1) viruses of the same genotype that had circulated in Europe 2022-2023. The A(H5N1) viruses collected from wild…”

Avian influenza overview March–June 2024

“…Details on the nomenclature of the HPAI A(H5) viruses used in this section are reported in Appendix B. Genotypes are assigned using the criteria described in Fusaro et al (2024). Mutation analyses of the A(H5N1) viruses have been performed using FluMut (Github izsvenezie-virology, online-a, b) with FluMutDB v5.0 mutation database.…”