Molecular Epidemiology and Evolutionary Trajectory of Emerging Echovirus 30, Europe

Abstract

In 2018, an upsurge in echovirus 30 (E30) infections was reported in Europe. We conducted a large-scale epidemiologic and evolutionary study of 1,329 E30 strains collected in 22 countries in Europe during 2016-2018. Most E30 cases affected persons 0-4 years of age (29%) and 25-34 years of age (27%). Sequences were divided into 6 genetic clades (G1-G6). Most (53%) sequences belonged to G1, followed by G6 (23%), G2 (17%), G4 (4%), G3 (0.3%), and G5 (0.2%). Each clade encompassed unique individual recombinant forms; G1 and G4 displayed >2 unique recombinant forms. Rapid turnover of new clades and recombinant forms occurred over time. Clades G1 and G6 dominated in 2018, suggesting the E30 upsurge was caused by emergence of 2 distinct clades circulating in Europe. Investigation into the mechanisms behind the rapid turnover of E30 is crucial for clarifying the epidemiology and evolution of these enterovirus infections.

Keywords: Europe; European Non-Polio Enterovirus Network; Molecular epidemiology; Nextstrain; echovirus 30; enterovirus; epidemiological monitoring; evolutionary trajectory; genetic recombination; meningitis/encephalitis; neurological manifestations; viruses; whole-genome sequencing.

Figure 1

Geographic distribution of echovirus 30 (EV30) clades, Europe, 2016–2018. Clades G1–G6 were detected among 1,329 EV30 cases from 22 countries. A) 2016; B) 2017; C) 2018.

Figure 2

Monthly distribution of echovirus 30 (EV30) clades G1–G6 detected among 1,329 sequences submitted from 22 countries in Europe during 2016–2018.

Figure 3

Phylodynamic analysis of region 1 in a curated study of echovirus 30 (E30) viral protein 1 (VP1) sequences from 22 countries in Europe, 2010–2018. We constructed the bootstrapped maximum likelihood neighbor-joining trees using 47 full length sequences and 277 VP1 sequences extracted from GenBank. E30 groups 1–8 are labeled. A) Maximum likelihood trees constructed by using MEGA version 7.0 (https://www.megasoftware.net). Prototype E30 strain Bastianni, (GenBank accession no. AF311938) was used as a reference. Scale bar indicates nucleotide substitutions per site. B) Maximum likelihood trees constructed by using Nextstrain (https://nextstrain.org) from which we dropped several problematic sequences, including group 5.

Figure 4

Neighbor-joining tree of 3D polymerase (3Dpol) sequences of echovirus 30 (E30) study samples and sequences from previously described E30 strains. The tree was constructed from Jukes-Cantor corrected nucleotide sequence distances in MEGA version 7.0 (https://www.megasoftware.net). Colored circles represent clades G1–G6 from this study; black circles represent 581 previously described E30 strains; and unlabeled branches represent all other species B types (n = 1,566) available in GenBank as of October 18, 2019. Scale bar indicates nucleotide substitutions per site.

Figure 5

Tanglegram of echovirus 30 (E30) phylogenetic virus protein 1 (VP1) (right) and 3D polymerase (3Dpol) (left) by year of sample collection. We used 110 sequences and rendered the tanglegram by using Nextstrain (https://www.nextstrain.org). Clades G1–G6 are labeled.