Complete Genome Sequence of a Human Enterovirus 71 Strain Isolated in Wuhan, China, in 2010

Zhu, Yan; Lu, Songya; Xian, Jianchun; Ye, Jun; Xiao, Li; Luo, Jun; Zen, Ke; Liu, Fenyong

doi:10.1128/genomea.01112-13

Cited by 8 publications

(6 citation statements)

References 16 publications

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“…Presence of a very rare N282D substitution in all 116Y sequences supports the aforementioned sequence of events and thus a single contamination event rather than introduction of two distinct virus variants, one with 116H and another with 116Y polymorphisms. The major N282D lineage included two hypothetical intermediate strains (Figure 3, N1 and N2), which further diverged into lineages found in Luan (Anhui province) in 2008 (sequences 2–4), the Yunnan province 2009 lineage (N3 ancestor and sequences 13 and 14), the Beijing 2009 lineage (Figure 3, sequences 5–8) [13], and the Hubei province 2009–2010 lineage (Figure 3, sequence 15) [11]. These lineages carried unique characteristic mutations and gained additional substitutions during circulation.…”

Section: Resultsmentioning

confidence: 99%

“…Apparently, the scale of virus circulation was extensive. All 15 isolates analyzed here came from hand, foot, and mouth disease (HFMD) patients, none of whom had neurological disease [11,12,13]. This small number of isolates does not allow ruling out neuropathogenicity of the Chinese GtA viruses.…”

Section: Discussionmentioning

confidence: 99%

“…Genotype A has been represented by a sole prototype strain (BrCr), which was identified in California, USA, during 1969–1972 [10]. Although the most recent cases in China were associated with subgenotype C4, several isolates belonged to genotype A, which had not been detected since 1972 [11,12,13]. The high degree of identity between the Chinese EV-A71 GtA and the prototype strain BrCr was suggestive of non-natural introduction [5].…”

Section: Introductionmentioning

confidence: 99%

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Using Statistical Phylogenetics for Investigation of Enterovirus 71 Genotype A Reintroduction into Circulation

Vakulenko

Deviatkin

Lukashev

2019

Viruses

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Using Statistical Phylogenetics for Investigation of Enterovirus 71 Genotype A Reintroduction into Circulation

Vakulenko

Deviatkin

Lukashev

2019

Viruses

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“…Another feature of enteroviruses is that the transmission of the prototype viruses is difficult to detect. In fact, we are unaware of any recent detections of the CV-A6 prototype Gdula or the CV-A16 prototype G-10; only a few cases of the EV-A71 prototype BrCr have been reported (39). The most plausible explanation for losing track of prototypic enteroviruses is that recombination is very beneficial for viral infection and replication, enabling viruses to outcompete their prototypes, whose infectivity is inferior.…”

Section: Discussionmentioning

confidence: 99%

Divergent Pathogenic Properties of Circulating Coxsackievirus A6 Associated with Emerging Hand, Foot, and Mouth Disease

Wang

et al. 2018

J Virol

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Coxsackievirus A6 (CV-A6) is an emerging pathogen associated with hand, foot, and mouth disease (HFMD). Its genetic characterization and pathogenic properties are largely unknown. Here, we report 39 circulating CV-A6 strains isolated in 2013 from HFMD patients in northeast China. Three major clusters of CV-A6 were identified and related to CV-A6, mostly from Shanghai, indicating that domestic CV-A6 strains were responsible for HFMD emerging in northeast China. Four full-length CV-A6 genomes representing each cluster were sequenced and analyzed further. Bootscanning tests indicated that all four CV-A6-Changchun strains were most likely recombinants between the CV-A6 prototype Gdula and prototype CV-A4 or CV-A4-related viruses, while the recombination pattern was related to, yet distinct from, the strains isolated from other regions of China. Furthermore, different CV-A6 strains showed different capabilities of viral replication, release, and pathogenesis in a mouse model. Further analyses indicated that viral protein 2C contributed to the diverse pathogenic abilities of CV-A6 by causing autophagy and inducing cell death. To our knowledge, this study is the first to report lethal and nonlethal strains of CV-A6 associated with HFMD. The 2C protein region may play a key role in the pathogenicity of CV-A6 strains. Hand, foot, and mouth disease (HFMD) is a major and persistent threat to infants and children. Besides the most common pathogens, such as enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16), other enteroviruses are increasingly contributing to HFMD. The present study focused on the recently emerged CV-A6 strain. We found that CV-A6 strains isolated in Changchun City in northeast China were associated with domestic origins. These Changchun viruses were novel recombinants of the CV-A6 prototype Gdula and CV-A4. Our results imply that measures to control CV-A6 transmission are urgently needed. Further analyses revealed differing pathogenicities in strains isolated in a neonatal mouse model. One of the possible causes has been narrowed down to the viral protein 2C, using phylogenetic studies, viral sequences, and direct tests on cultured human cells. Thus, the viral 2C protein is a promising target for antiviral drugs to prevent CV-A6-induced tissue damage.

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“…Although most of the patients recover on their own within 1–2 weeks, complications like viral encephalitis, brain stem encephalitis, pulmonary edema, and acute flaccid paralysis or even death have been reported in minor infants and children [ 5 , 6 ]. Since the isolation and identification of the first strain of EV71 in 1969 from the Americas [ 7 ], numerous outbreaks of the virus have been reported worldwide [ 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. The virus has become highly prevalent in the Western Pacific region after the outbreak in Taiwan in 1997, persistently causing seasonal outbreaks with enhanced severity and mortality [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Cross-Antigenicity between EV71 Sub-Genotypes: Implications for Vaccine Efficacy

Liu

Yuan

Cui

et al. 2021

Viruses

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Enterovirus A-71 (EV71) is a global, highly contagkkious pathogen responsible for severe cases of hand-food-mouth-disease (HFMD). The use of vaccines eliciting cross neutralizing antibodies (NTAbs) against the different circulating EV71 sub-genotypes is important for preventing HFMD outbreaks. Here, we tested the cross-neutralizing activities induced by EV71 genotype/sub-genotype A, B0-B4, C1, C2, C4, and C5 viruses using rats. Differences were noted in the cross-neutralization of the 10 sub-genotypes tested but there were generally good levels of cross-neutralization except against genotype A virus, against which neutralization antibody titres (NTAb) where the lowest with NTAbs being the highest against sub-genotype B4. Moreover, NTAb responses induced by C4, B4, C1, and C2 viruses were homogenous, with values of maximum/minimum NTAb ratios (MAX/MIN) against all B and C viruses ranging between 4.0 and 6.0, whereas MAX/MIN values against B3 and A viruses were highly variable, 48.0 and 256.0, respectively. We then dissected the cross-neutralizing ability of sera from infants and children and rats immunized with C4 EV71 vaccines. Cross-neutralizing titers against the 10 sub-genotypes were good in both vaccinated infants and children and rats with the MAX/MIN ranging from 1.8–3.4 and 5.1–7.1, respectively, which were similar to those found in naturally infected patients (2.8). Therefore, we conclude that C4 EV71 vaccines can provide global protection to infants and children against HFMD caused by different sub-genotypes.

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Complete Genome Sequence of a Human Enterovirus 71 Strain Isolated in Wuhan, China, in 2010

Cited by 8 publications

References 16 publications

Using Statistical Phylogenetics for Investigation of Enterovirus 71 Genotype A Reintroduction into Circulation

Using Statistical Phylogenetics for Investigation of Enterovirus 71 Genotype A Reintroduction into Circulation

Divergent Pathogenic Properties of Circulating Coxsackievirus A6 Associated with Emerging Hand, Foot, and Mouth Disease

Cross-Antigenicity between EV71 Sub-Genotypes: Implications for Vaccine Efficacy

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