Genomic epidemiology of West Nile virus in Europe

Abstract

West Nile virus is one of the most widespread mosquito-borne zoonotic viruses, with unique transmission dynamics in various parts of the world. Genomic surveillance has provided important insights in the global patterns of West Nile virus emergence and spread. In Europe, multiple West Nile virus lineages have been isolated, with lineage 1a and 2 being the main lineages responsible for human infections. In contrast to North America, where a single introduction of lineage 1a resulted in the virus establishing itself in a new continent, at least 13 introductions of lineages 1a and 2 have occurred into Europe, which is likely a vast underestimation of the true number of introductions. Historically, lineage 1a was the main lineage circulating in Europe, but since the emergence of lineage 2 in the early 2000s, the latter has become the predominant lineage. This shift in West Nile virus lineage prevalence has been broadly linked to the expansion of the virus into northerly temperate regions, where autochthonous cases in animals and humans have been reported in Germany and The Netherlands. Here, we discuss how genomic analysis has increased our understanding of the epidemiology of West Nile virus in Europe, and we present a global Nextstrain build consisting of publicly available West Nile virus genomes (https://nextstrain.org/community/grubaughlab/WNV-Global). Our results elucidate recent insights in West Nile virus lineage dynamics in Europe, and discuss how expanded programs can fill current genomic surveillance gaps.

Keywords: Epidemiology; Europe; Genomic surveillance; West Nile virus.

Fig. 1

Global phylogeny of West Nile virus lineages. A) Phylogenetic tree of all available whole genome sequences available on GenBank (USA downsampled). B) Geographic map of all sequences included in the phylogenetic tree. Missing metadata was supplemented from various sources please see GitHub repository for more details: https://github.com/grubaughlab/WNV-global.

Fig. 2

Temporal trends in reported human cases of West Nile virus in Europe. Yearly West Nile cases in Europe as reported by the European Centre for Disease Prevention and Control (ECDC) [40]. Only confirmed human cases based on laboratory tests for case confirmation are shown.

Fig. 3

Global sequencing of West Nile virus over time. We used GenBank to download all partial (e.g. Envelope and NS5 <7700 base pairs) and near-complete genomes (>7700 base pairs (i.e. >70% genome completeness)) from Africa, Asia, the Americas, and Europe from 1937 to 2022. The Americas includes South and North America and Asia includes Australia. Russia is counted in Europe as most cases occur in the Volgograd region near the Ukrainian border. The Genome Detective West Nile virus typing tool was used to assign lineages. “Other” samples include lineage 3 (Rabensburg), lineage 4, lineage 7 (Koutango), and lineage 8.

Fig. 4

West Nile virus intercontinental introductions into Europe. A) Time series of West Nile virus introductions into Europe. Introductions were identified in the Nexstrain build and verified with previous research. Lineages were assigned using the Genome Detective West Nile virus typing tool, with lineage 1a in blue and lineage 2 in pink. Square shaped points indicate the inferred introduction year, diamond shaped points indicate the first sample sequenced in the clade, and circle indicates the last sequenced sample from that clade. Y-axis labels indicate the country of introduction, and the size of the circles and number within the circles indicates the number of whole genome sequences identified within each clade. B) Lineages 1 and 2 phylogenetic trees with corresponding introductions labeled from A. Virus clades can be visualized on Nextstrain https://nextstrain.org/community/grubaughlab/WNV-Global. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 5

Intracontinental West Nile virus lineage dynamics. A) Time series of European partial and whole genomes available on NCBI GenBank that included collection date and location. B) Map of European partial and whole genomes available on NCBI GenBank that included collection date and location. Lineages were assigned using the Genome Detective West Nile virus typing tool [17].