Investigating the Genetic Diversity of H5 Avian Influenza Viruses in the United Kingdom from 2020-2022

Abstract

Since 2020, the United Kingdom and Europe have experienced annual epizootics of high-pathogenicity avian influenza virus (HPAIV). The first epizootic, during the autumn/winter of 2020-2021, involved six H5Nx subtypes, although H5N8 HPAIV dominated in the United Kingdom. While genetic assessments of the H5N8 HPAIVs within the United Kingdom demonstrated relative homogeneity, there was a background of other genotypes circulating at a lower degree with different neuraminidase and internal genes. Following a small number of detections of H5N1 in wild birds over the summer of 2021, the autumn/winter of 2021-2022 saw another European H5 HPAIV epizootic that dwarfed the prior epizootic. This second epizootic was dominated almost exclusively by H5N1 HPAIV, although six distinct genotypes were defined. We have used genetic analysis to evaluate the emergence of different genotypes and proposed reassortment events that have been observed. The existing data suggest that the H5N1 viruses circulating in Europe during late 2020 continued to circulate in wild birds throughout 2021, with minimal adaptation, but then went on to reassort with AIVs in the wild bird population. We have undertaken an in-depth genetic assessment of H5 HPAIVs detected in the United Kingdom over two winter seasons and demonstrate the utility of in-depth genetic analyses in defining the diversity of H5 HPAIVs circulating in avian species, the potential for zoonotic risk, and whether incidents of lateral spread can be defined over independent incursions of infections from wild birds. This provides key supporting data for mitigation activities. IMPORTANCE High-pathogenicity avian influenza virus (HPAIV) outbreaks devastate avian species across all sectors, having both economic and ecological impacts through mortalities in poultry and wild birds, respectively. These viruses can also represent a significant zoonotic risk. Since 2020, the United Kingdom has experienced two successive outbreaks of H5 HPAIV. While H5N8 HPAIV was predominant during the 2020-2021 outbreak, other H5 subtypes were also detected. The following year, there was a shift in the subtype dominance to H5N1 HPAIV, but multiple H5N1 genotypes were detected. Through the thorough utilization of whole-genome sequencing, it was possible to track and characterize the genetic evolution of these H5 HPAIVs in United Kingdom poultry and wild birds. This enabled us to assess the risk posed by these viruses at the poultry-wild bird and the avian-human interfaces and to investigate the potential lateral spread between infected premises, a key factor in understanding the threat to the commercial sector.

Keywords: WGS; avian influenza; genomics; high-pathogenicity.

FIG 1

Geographic distribution of H5Nx AIVs that were sequenced during 2020 to 2022. Shown are the geographic distributions of H5Nx AIVs that were sequenced from wild birds (A and C) and poultry (B and D) during the 2020–2021 (A and B) and 2021–2022 (C and D) epizootics in the United Kingdom. Locations are colored according to the AIV subtype and pathotype.

FIG 2

The HA of the H5Nx HPAIVs from 2020–2022 were derived from a common ancestor. Shown is a time-resolved maximum likelihood phylogenetic tree of the HA gene from H5Nx AIVs collected from the United Kingdom between 2020 and 2022, with relevant global reference sequences. The tips are colored according to AIV subtype, and the sequences obtained from either the 2020–2021 or the 2021–2022 H5 HPAIV epizootics are indicated. For the H5N1 HPAIV sequences, the B1 and B2 sublineages are also shown.

FIG 3

H5Nx AIVs from the United Kingdom collected between 2020 and 2022 demonstrate wide genotypic diversity. (A) Phylogenetic incongruence analysis of H5Nx sequences from the United Kingdom for AIVs collected between 2020 and 2022. Maximum likelihood phylogenetic trees for all gene segments from each strain are connected across the trees, with tips and connecting lines colored according to genotype. (B) Schematic representation of the different H5Nx genotypes from the United Kingdom between 2020 and 2022. Note that while the HA gene of the H5N1 HPAIV B2 sublineage is colored differently for the purposes of this diagram, it is still derived evolutionarily from the A/chicken/Iraq/1/2020 H5N8 HPAIV HA gene. (C and D) Numbers of sequences for each UK H5Nx genotype generated during the 2020–2021 (C) and 2021–2022 (D) epizootics.

FIG 4

Analysis of H5Nx sequences suggests limited lateral transmission between geographically related HPAIV detections. Shown are outputs of the BSSVS analysis for the seven geographic clusters of H5Nx HPAIV detections investigated for the potential of lateral transmission to have occurred. Each geographic cluster is represented by a separate network diagram using the relative location of each infected premises (IP) or wild bird (WB) detection. Arrows are colored according to the relative strength, inferred using a Bayes factor (BF), by which the transmission rates are supported. Scale bars are provided for each cluster, representing 1 km.