Molecular Epidemiology of Echovirus 30: Temporal Circulation and Prevalence of Single Lineages

Abstract

Echovirus 30 (EV30) is one of the most frequently isolated EVs, causing extensive outbreaks of EV30 aseptic meningitis in temperate climates. EV30 is antigenically heterogeneous, and three major antigenic groups have been defined, although the basis for the antigenic differences is unknown. A reverse transcription-nested PCR which amplifies the 3-terminal region of the VP1 gene directly from clinical samples was selected for studying EV30 molecular epidemiology, since the major antigenic sites in this region reflect the serotypic pattern of this virus. The different previous approaches to the genetic classification of EV30 were analyzed. A complete study of the EV30 strains was performed by analyzing the sequences from the 112 EV30 strains amplified in this work and the complete set of EV30 strains previously published. A total of 318 strains of EV30 were divided into two broad genotypes (I and II). This classification was supported by the phylogenetic trees obtained from amino acid sequences, and it correlated with the antigenic heterogeneity of the reference strains described in earlier studies. The genotypes could be further divided into subgroups, and these subgroups could be divided into lineages based on their nucleotide distances and levels of bootstrapping. On the other hand, the subgroups and lineages did not result in the same correlation between amino acid and nucleotide differentiation. The molecular epidemiology of EV30 can be compared to influenza virus epidemiology, where prevailing lineages displace the less established lineages on the basis of immune escape. This pattern of evolution is clearly different from that of other enteroviruses. A single lineage at a time appears to be circulating worldwide. This behavior may be related to the epidemic activity of EV30.Human enteroviruses (HEVs) are small RNA viruses of the Picornaviridae family. Genetic and phylogenetic analysis of the capsid-encoding region VP1 showed four clusters: (i) HEV-A, including 11 coxsackie A viruses (CAVs) and enterovirus 71; (ii) HEV-B, including all coxsackie B viruses (CBVs), all echoviruses (EVs), enterovirus 69, and CAV9; (iii) HEV-C, including all polioviruses and 11 other CAVs; and (iv) HEV-D, including enteroviruses 68 and 70. The common transmission routes may be direct, by fecal-oral and respiratory spread, and indirect, by fomites and contaminated water. Enterovirus infections generally go unnoticed, complicating their differential diagnosis. Infection occasionally leads to severe disorders such as meningitis, encephalitis, pleurodynia, myocarditis, conjunctivitis, or severe systemic infections in neonates (7).Echovirus 30 (EV30) is one of the most frequently isolated EVs, causing extensive outbreaks of EV30 aseptic meningitis in temperate climates in several countries (10, 16). Additionally, this serotype is one of several enteroviruses associated with sporadic cases of aseptic meningitis (5). EV30 is antigenically heterogeneous, and three major antigenic groups have been defined (6, 17), although the basis for t...

Transmission Networks and Population Turnover of Echovirus 30

“…Comparison of VP1 sequences from previous studies allowed the main clades to be matched to previously assigned genotypes or lineages. The majority (318/325) of variants analyzed in the study fell into previously assigned E30 genotype II cluster of VP1 sequences, with most falling into the H lineage and smaller numbers in the E, F, and G VP1 subgroups designated in previous studies (8,42). These correspond to VP1 lineages classified as C0 to C4 (32) or 3a to 3d (49 VP1 sequences from the main E30 group in the sequenced region of VP1 showed approximately 9% nucleotide sequence divergence (mean pairwise P distance), with variability almost entirely restricted to synonymous sites (nonsynonymous to synonymous substitution [dN/dS] ratio based on uncorrected synonymous and nonsynonymous distances of 0.04).…”

“…Further from Europe, in Southeast Asia, E30 variants in Malaysia (this study), Taiwan (11), and China (60) Because of the number of sequences (Ͼ300), only those showing greater than 1.0% or 1.5% divergence, respectively, from each other are shown. Dot colors indicate the 3Dpol clade of the displayed sequences (see text), not the H, E, F, and G VP1 subgroups assigned in previous analyses (8,42). 3Dpol region sequences of study subjects were interspersed with sequences from other species B serotypes and have been included in panel B, labeled with the following abbreviations: E, echoviruses; CVA, coxsackie virus type A; CVB, coxsackie virus type B; EV, new enteroviruses.…”

Molecular Analysis of Enteroviruses

“…Since its characterization in 1958, E30 has been increasingly associated with meningitis outbreaks worldwide [88]. Several studies have shown different clustering of E30 variants based on VP1 and/or 5' UTR sequences [18, [89][90][91].…”

Circulation of two Enterovirus C105 (EV-C105) lineages in Europe and Africa

“…Following principles previously applied in Echovirus 30 analysis (Palacios et al, 2002), EV-C105 strains were divided into lineages based on pairwise distances: (1) lineage A consisting of Pavia/8376, Pavia/9095 and ROM31 strains and (2) lineage B including BU77 and BU5 strains. The distribution of pairwise distances along the entire genome was similar for the three European EV-C105 strains (group A), while the degree of nucleotide identity between the African strains (group B) and the reference strain (34S) for the P2 and P3 regions (81.8-83.2 %) was lower than that for the P1 region (83.9-84.0 %).…”