What is the clinical evidence from this study?

Study design: Observational. Population: Human enterovirus 71 (EV-A71) (n=3346). Intervention: Phylogenetic and evolutionary analysis of VP1 sequences. Primary outcome: Classification of EV-A71 isolates into genogroups based on VP1 nucleotide sequence divergence.

March 5, 2014PLoS ONE132 citationsOpen Access

Molecular Comparison and Evolutionary Analyses of VP1 Nucleotide Sequences of New African Human Enterovirus 71 Isolates Reveal a Wide Genetic Diversity

MBMaël BessaudCentre National de la Recherche Scientifique RRRichter RazafindratsimandresyInstitut Pasteur de Madagascar ANAntoine NougaırèdeInserm

Key Result

Phylogenetic analysis of 3,346 EV-A71 VP1 sequences revealed three new genogroups (D, E, and F) in addition to the known genogroups A-C, indicating a wider genetic diversity than previously recognized.

Study Design

Type

Observational (n=3,346)

Structured PICO

Population

3,346 complete VP1 nucleotide sequences of Human enterovirus 71 isolates collected globally, including new isolates from Madagascar and India, analyzed to determine genetic diversity and evolutionary history.

Outcome

Genetic diversity and phylogenetic classification of EV-A71 isolates

The study reveals a wider genetic diversity among EV-A71 isolates than previously recognized, identifying new genogroups particularly in developing countries.

Limitations

Redundant sequences were not discarded, so the dataset may contain identical sequences from a single isolate.
The time origin of the virus remains uncertain due to large credibility intervals of the TMRCA.
Genotyping based solely on the VP1 gene does not account for recombination events in the non-structural part of the genome.
Putative additional genogroups in India were based on partial VP1 sequences and require confirmation with longer sequences.

Abstract

Most circulating strains of Human enterovirus 71 (EV-A71) have been classified primarily into three genogroups (A to C) on the basis of genetic divergence between the 1D gene, which encodes the VP1 capsid protein. The aim of the present study was to provide further insights into the diversity of the EV-A71 genogroups following the recent description of highly divergent isolates, in particular those from African countries, including Madagascar. We classified recent EV-A71 isolates by a large comparison of 3,346 VP1 nucleotidic sequences collected from GenBank. Analysis of genetic distances and phylogenetic investigations indicated that some recently-reported isolates did not fall into the genogroups A-C and clustered into three additional genogroups, including one Indian genogroup (genogroup D) and 2 African ones (E and F). Our Bayesian phylogenetic analysis provided consistent data showing that the genogroup D isolates share a recent common ancestor with the members of genogroup E, while the isolates of genogroup F evolved from a recent common ancestor shared with the members of the genogroup B. Our results reveal the wide diversity that exists among EV-A71 isolates and suggest that the number of circulating genogroups is probably underestimated, particularly in developing countries where EV-A71 epidemiology has been poorly studied.

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