Abstract

Neurovirulent enterovirus 71 (EV-A71) caused a massive epidemic in China in 2008–2011. While subgenotype C4 was the major causative agent, a few isolates were almost identical to the prototype EV-A71 strain and belonged to genotype A. This variant was allegedly extinct since 1970, and its identification in this epidemic suggests reintroduction of the archive virus. Regression analysis of genetic distances (TempEst software) was of moderate utility due to the low resolution of classical phylogenetic methods. Bayesian phylogenetic analysis (BEAST software) suggested artificial introduction event based on highly aberrant phylogenetic tree branch rates that differed by over three standard deviations from the mean substitution rate for EV71. Manual nucleotide-level analysis was used to further explore the virus spread pattern after introduction into circulation. Upon reintroduction, the virus accumulated up to seven substitutions in VP1, most of them non-synonymous and located within the capsid’s canyon or at its rims, compatible with readaptation of a lab strain to natural circulation.

Highlights

  • Enterovirus 71 (EV-A71) belongs to the Enterovirus A species

  • We created an alignment that comprised all EV-A71 sequences downloaded from GenBank that shared less than

  • In of Venezuelan equine encephalitis introduction, it was suggested to use the regression line slope to the investigation of Venezuelan equine encephalitis introduction, it was suggested to use the infer nucleotide sequence change rates and non-natural evolutionary events in certain sequence regression line slope to infer nucleotide sequence change rates and non-natural evolutionary groups [39]; this parameter may be dependent upon the dataset and is difficult to evaluate events in certain sequence groups [39]; this parameter may be dependent upon the dataset statistically, and requires that there is a group of “artificial” sequences, which may not be and is difficult to evaluate statistically, and requires that there is a group of “artificial”

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Summary

Introduction

Enterovirus 71 (EV-A71) belongs to the Enterovirus A species. This species, which includes a number of Coxsackie A viruses and enteroviruses, is a member of the genus Enterovirus of the familyPicornaviridae. Enterovirus 71 (EV-A71) belongs to the Enterovirus A species. This species, which includes a number of Coxsackie A viruses and enteroviruses, is a member of the genus Enterovirus of the family. EV-A71 is one of the main causative agents of hand, foot, and mouth disease (HFMD). May cause severe neurological complications such as brainstem encephalitis and acute flaccid paralysis [1,2]. In 2008–2011, regular EV-A71 epidemics that involved over a million cases occurred in. EV-A71 is the most represented enterovirus type in GenBank, with over 11,000 partial genomic sequences out of approximately 70,000 enterovirus sequences [4]. According to the genetic distance and phylogenetic relations in the genome region that encodes the major capsid protein

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