Molecular epidemiology analysis of enterovirus 71 strains isolated in Dak Lak, Vietnam, 2011‐2016

Abstract

Human enterovirus 71 (EV71) is the major etiologic agent of hand, foot, and mouth disease (HFMD). EV71 outbreaks have been reported in Dak Lak in recent years, however, the genotypes/subgenotypes information and phylogeny of circulating EV71 strains are limited. The objectives of this study were to determine the genotypes/subgenotypes and investigate the phylogeny of EV71 isolates in Dak Lak over a 6-year period. Viruses were isolated from clinical samples from patients with HFMD. In total, 43 EV71 isolates circulated in Dak Lak during 2011-2016 were used for the phylogenetic analysis using complete VP1 gene. The phylogenetic analysis of the VP1 gene revealed that two major genotypes, B and C, were found. Among the 43 EV71 strains, 29 belonged to subgenotype C4, 2 belonged to subgenotype C5, and 12 belonged to subgenotype B5. Of these, the subgenotype C4 was predominant in 2011-2013 and this was later replaced by the subgenotype B5 in 2014. The subgenotype B5 was dominant between 2014 and 2015, and then C4 recirculated in 2016. Our study also indicated that the subgenotypes C4 and B5 emerged into Dak Lak were closely related to variants causing epidemics of HFMD in the southern and central region of Vietnam and Thailand. Sequence analysis showed that nine amino acid mutations were detected in the VP1 region. Our results identified two significant amino acid substitutions (D31N and E145G/Q) associated with enhancing EV71 virulence.

Genetic Variation of Multiple Serotypes of Enteroviruses Associated with Hand, Foot and Mouth Disease in Southern China

“…Among these VPs, the VP1 region of EVs is most often used for genotyping (Harvala et al 2018 ). EV-A71, the most common pathogen of severe HFMD, is divided into seven genogroups, A through G; eleven subgenogroups, B0 through B5 and C1 through C5; and two sublineages, C4a and C4b, based on the VP1 region (Iwai et al 2009 ; Zhu et al 2013 ; Le et al 2019 ). The prototype strain for EV-A71 is BrCr.…”

Molecular characteristics of VP1 region of enterovirus 71 strains in China

“…It has been reported that the E98K mutation may increase the hydrophobicity of VP1, making it easy for large compounds to enter and interfere with VP1 receptor binding, suggesting that E98K mutant viruses are sensitive to larger compounds [40]. Other studies have shown that E145G and N31D mutations are associated with increased virulence of EV71 and may increase the risk of neurological complications, while I262V mutations reduce the risk of neurological complications [41][42][43]. In this study, the mutation rates of E98K, E145G, N31D and I262V were 6.65%, 3.13%, 7.25% and 2.77%, respectively.…”

Enterovirus infection in the Socialist Republic of Vietnam

“…В настоящее время в международных базах данных опубликовано более тысячи (1004) нуклеотидных последовательностей области VP1 генома, кодирующего этот полипротеин, или полного генома штаммов вируса EV-A71, циркулировавшего во Вьетнаме в 2003-2016 гг. В этот период была зафиксирована циркуляция энтеровируса EV-A71 генотипов С1, С4, С5 и В5 [12,13,16,17,23,28,31,33]. В 2003-2010 гг.…”

“…Рост заболеваемости HFMD во Вьетнаме с увеличением числа случаев с летальным исходом наблюдался в 2011-2012 гг. -на пике активности циркуляции вируса EV-A71 генотипа С4 [12,13,15,16,17,23,25]. В 2011 г. на территории Вьетнама было зафиксировано начало циркуляции вируса EV-A71 генотипа В5, который в 2013 г. стал доминирующим [12,23].…”