Population Dynamics and Genetic Diversity of C4 Strains of Human Enterovirus 71 in Mainland China, 1998–2010

Dawei Guan,Zheng Liu,Sabine Van Der Sanden,Wei Li,Changwen Ke,Hanri Zeng,Huanying Zheng,Marion Koopmans,Cong Ma,Xue Guo,Xin Zhang,Leng Liu,Juan Su,Yury E Khudyakov

doi:10.1371/journal.pone.0044386

Abstract

BackgroundSince 1997, several countries within the Asian Pacific region have been affected by one or more massive outbreaks of Hand Foot and Mouth Disease (HFMD). Virus typing experiments revealed that these outbreaks were caused by strains of human enterovirus 71 (EV71) belonging to several different, recently emerged subgenogroups. In mainland China, a different situation was observed. The first outbreak, localized in Shangdong Province, was reported in 2007, and was followed by a wide-spread outbreak in mainland China in 2008. Since then, numbers of reported HFMD cases have been persistently high.Methodology/Principal FindingsTo gain insight in the epidemiological behavior of EV71 in China, we studied genetic diversity and EV71 population dynamics to address whether the increase in number of reported EV71 infections reflects a real increase in viral spread or is just the result of increased awareness and surveillance. We used systematically collected VP1 gene sequences of 257 EV71 strains collected in Guangdong province from 2008 to 2010 as part of HFMD surveillance activities, and supplemented them with 305 GenBank EV71 reference stains collected in China from 1998 to 2010. All isolates from Guangdong Province belonged to subgenogroup C4. Viral population dynamics indicated that the increased reporting of HFMD in China since 2007 reflects a real increase in viral spread and continued replacement of viral lineages through time. Amino acid sequence comparisons revealed substitution of amino acid in residues 22, 145 and 289 through time regularly with the VP1 gene of EV71 strains isolated in mainland China from 1998 to 2010.ConclusionsEV71 strains isolated in mainland China mainly belonged to subgenogroup C4. There was exponential growth of the EV71 virus population in 2007 and 2008. There was amino acid substitution through time regularly with the VP1 gene which possibly increased viral spread and/or ability of the virus to circulate persistently among the Chinese population.

Highlights

Human enterovirus 71, belonging to the Human enterovirus A species of the genus Enterovirus of the family Picornaviridae, is a major causative agent of hand, foot and mouth disease (HFMD) [1,2]
enterovirus 71 (EV71) strains isolated in mainland China mainly belonged to subgenogroup C4
Different from other enteroviruses causing Hand Foot and Mouth Disease (HFMD), like Coxsackievirus A16, infections with EV71 can progress to severe neurological disease, including brainstem encephalitis and poliomyelitis-like paralysis [3,4,5,6,7,8,9,10]

Summary

Introduction

Human enterovirus 71, belonging to the Human enterovirus A species of the genus Enterovirus of the family Picornaviridae, is a major causative agent of hand, foot and mouth disease (HFMD) (usually in children aged ,5 years) [1,2]. Human enterovirus 71 was identified for the first time in the USA in 1969, and since EV71-associated neurological disease has been observed in outbreaks throughout the world [1,2,4,8,11,12,13,14,15,16,17]. Virus typing experiments revealed that these outbreaks were caused by strains of human enterovirus 71 (EV71) belonging to several different, recently emerged subgenogroups. Numbers of reported HFMD cases have been persistently high

Methods

Results

Conclusion