Molecular evolution of the major capsid protein VP1 of enterovirus 70

Abstract

Nucleotide sequences of the genome RNA encoding capsid protein VP1 (918 nucleotides) of 18 enterovirus 70 (EV70) isolates collected from various parts of the world in 1971 to 1981 were determined, and nucleotide substitutions among them were studied. The genetic distances between isolates were calculated by the pairwise comparison of nucleotide difference. Regression analysis of the genetic distances against time of isolation of the strains showed that the synonymous substitution rate was very high at 21.53 X 10-3 substitution per nucleotide per year, while the nonsynonymous rate was extremely low at 0.32 X 10-3 substitution per nucleotide per year. The rate estimated by the average value of synonymous and nonsynonymous substitutions (W.-H. Li, C.-C. Wu, and C.-C. Luo, Mol. Biol. Evol. 2:150-174, 1985) was 5.00 X 10-3 substitution per nucleotide per year. Taking the average value of synonymous and nonsynonymous substitutions as genetic distances between isolates, the phylogenetic tree was inferred by the unweighted pairwise grouping method of arithmetic average and by the neighbor-joining method. The tree indicated that the virus had evolved from one focal place, and the time of emergence was estimated to be August 1967 ± 15 months, 2 years before first recognition of the pandemic of acute hemorrhagic conjunctivitis. By superimposing every nucleotide substitution on the branches of the phylogenetic tree, we analyzed nucleotide substitution patterns of EV70 genome RNA. In synonymous substitutions, the proportion of transitions, i.e., C<->U and G*->A, was found to be extremely frequent in comparison with that reported on other viruses or pseudogenes. In addition, parallel substitutions (independent substitutions at the same nucleotide position on different branches, i.e., different isolates, of the tree) were frequently found in both synonymous and nonsynonymous substitutions. These frequent parallel substitutions and the low nonsynonymous substitution rate despite the very high synonymous substitution rate described above imply a strong restriction on nonsynonymous substitution sites of VP1, probably due to the requirement for maintaining the rigid icosahedral conformation of the virus.

Echovirus 30, Jiangsu Province, China

“…This finding strongly suggests that echovirus 30 was the etiologic agent in this outbreak. The distinct lineage of echovirus 30 reported in this outbreak is not surprising, given that genomes of enteroviruses are known to evolve by ≈1%-2% per year (28)(29)(30), and interserotypic recombination contributes to evolution of these viruses (31)(32)(33). The FDJS03 isolates may represent possible recombinants between echovirus 30 and other serotypic enteroviruses.…”

Molecular characterization of coxsackievirus B5 isolates

“…Several studies showed that genomic sequencing in the VP1 gene correlates with the enterovirus serotype; these studies included prototype strains as well as clinical isolates [Oberste et al, 1998[Oberste et al, , 1999aBrown et al, 1999;Bailly et al, 2000;Caro et al, 2001;Norder et al, 2001]. Molecular characterization and phylogenetic studies were conducted on Coxsackievirus A9 and 24, Coxsackievirus B4, Echovirus 30, and enterovirus type 70 and 71 [Ishiko et al, 1992;Hughes et al, 1993;Takeda et al, 1994;Brown et al, 1999;Santti et al, 2000;Wang et al, 2002] while published studies on the molecular epidemiology of Coxsackievirus B5 remain few and were carried out on field isolates from a restricted geographical origin [Kopecka et al, 1995]. In the present study, Coxsackievirus B5 isolated from North Africa and Romania were analyzed by partial sequencing in the VP1 region of the genome, and the sequences were compared to other published sequences from the same serotype, the major aim being the characterization of the molecular epidemiology and the evolution of Coxsackievirus B5, which is one of the most commonly isolated enterovirus serotypes in humans.…”

Prisoners of war — host adaptation and its constraints on virus evolution

“…As an early example of this phenomenon, the distance from the tree root of sequences of enterovirus 70 isolates collected through the 1970s and 1980s showed a linear relationship with collection date; the calculated nucleotide substitution rate of 5 × 10 −3 substitutions per site per year (SSY) allowed the start of the outbreak to be dated to 1967 (ref. 8 ). The availability of virus samples collected over relatively wide date ranges, often stretching back to the 1950s or 1960s, has enabled more sophisticated Bayesian methods (for example, Bayesian evolutionary analysis by sampling trees (BEAST) 9,10 ) to estimate dates of origins and substitution rates for a wide range of viruses associated with recent outbreaks.…”