Fourteen types of co-circulating recombinant enterovirus were associated with hand, foot, and mouth disease in children from Wenzhou, China

Guo, Wen‐Ping; Lin, Xian-Dan; Chen, Yiping; Liu, Qi; Wang, Wen; Wang, Cai-Qiao; Li, Minghui; Sun, Xiaoyu; Shī, Mǎng; Holmes, Edward C.; Zhāng, Yǒng-Zhèn

doi:10.1016/j.jcv.2015.06.093

Cited by 45 publications

(38 citation statements)

References 44 publications

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“…In contrast, our analysis of Ͼ100 complete EV-D68 genomes provided compelling evidence for recombination between outbreak subclade B1 and endemic subclade B2 strains, with a breakpoint in VP2. In recombination events in other enteroviruses, most breakpoints have been documented between the structural and nonstructural regions, or within the nonstructural region (44,67). Interestingly, the previous report of phylogenetic incongruence between the 5= UTR and VP1 in EV-D68 suggests the possibility of a recombination event within the structural region (22), although this clearly needs to be confirmed.…”

Section: Discussionmentioning

confidence: 97%

Molecular Evolution and Intraclade Recombination of Enterovirus D68 during the 2014 Outbreak in the United States

Tan

Hassan

Schuster

et al. 2016

J Virol

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In August 2014, an outbreak of enterovirus D68 (EV-D68) occurred in North America, causing severe respiratory disease in children. Due to a lack of complete genome sequence data, there is only a limited understanding of the molecular evolution and epidemiology of EV-D68 during this outbreak, and it is uncertain whether the differing clinical manifestations of EV-D68 infection are associated with specific viral lineages. We developed a high-throughput complete genome sequencing pipeline for EV-D68 that produced a total of 59 complete genomes from respiratory samples with a 95% success rate, including 57 genomes from Kansas City, MO, collected during the 2014 outbreak. With these data in hand, we performed phylogenetic analyses of complete genome and VP1 capsid protein sequences. Notably, we observed considerable genetic diversity among EV-D68 isolates in Kansas City, manifest as phylogenetically distinct lineages, indicative of multiple introductions of this virus into the city. In addition, we identified an intersubclade recombination event within EV-D68, the first recombinant in this virus reported to date. Finally, we found no significant association between EV-D68 genetic variation, either lineages or individual mutations, and a variety of demographic and clinical variables, suggesting that host factors likely play a major role in determining disease severity. Overall, our study revealed the complex pattern of viral evolution within a single geographic locality during a single outbreak, which has implications for the design of effective intervention and prevention strategies. IMPORTANCEUntil recently, EV-D68 was considered to be an uncommon human pathogen, associated with mild respiratory illness. However, in 2014 EV-D68 was responsible for more than 1,000 disease cases in North America, including severe respiratory illness in children and acute flaccid myelitis, raising concerns about its potential impact on public health. Despite the emergence of EV-D68, a lack of full-length genome sequences means that little is known about the molecular evolution of this virus within a single geographic locality during a single outbreak. Here, we doubled the number of publicly available complete genome sequences of EV-D68 by performing high-throughput next-generation sequencing, characterized the evolutionary history of this outbreak in detail, identified a recombination event, and investigated whether there was any correlation between the demographic and clinical characteristics of the patients and the viral variant that infected them. Overall, these results will help inform the design of intervention strategies for EV-D68.

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Section: Discussionmentioning

confidence: 97%

Molecular Evolution and Intraclade Recombination of Enterovirus D68 during the 2014 Outbreak in the United States

Tan

Hassan

Schuster

et al. 2016

J Virol

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“…Although the results were different from those found in previous studies conducted in China [18], a common feature was that the HEV-B species accounted for a large proportion (75–87%) of the population in Yunnan. Among them, nine serotypes (55.6%, 73/131) were related to HFMD [26–29], and no EV-A71 and CV-A16 were detected in healthy persons. The other two serotypes (CV-A4 and E-25) were detected at a low frequency in both healthy persons and patients with HFMD.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, a large number of EV-A71 (51.81%) and CV-A16 (32.53%) isolates, which were the major pathogens of HFMD in the study area, were found in patients with HFMD. In addition, CV-A10 and CV-A6, which were the secondary causes of HFMD, did not appear in healthy subjects [4, 26–31]. …”

Section: Discussionmentioning

confidence: 99%

Prevalence of enteroviruses in healthy populations and excretion of pathogens in patients with hand, foot, and mouth disease in a highly endemic area of southwest China

Jiang

et al. 2017

PLoS ONE

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Etiological carriers and the excretion of the pathogens causing hand, foot, and mouth disease (HFMD) in healthy persons, patients, and asymptomatic persons infected with HFMD as ongoing infection sources may play an important role in perpetuating and spreading epidemics of HFMD. The aims of this study were to determine the carrier status of EV-A71 and CV-A16 in healthy populations, as well as the duration of EV-A71 and CV-A16 shedding in the stools of HFMD patients in an epidemic area of southwest China. A cross-sectional study and a follow-up study were conducted in three HFMD endemic counties of Yunnan Province. Six hundred sixty-seven healthy subjects were recruited to participate in the cross-sectional study, and two stool specimens were collected from each subject. Among the healthy subjects, 90 (13.5%) tested positive for viral isolation, but neither EV-A71 nor CV-A16 was detected in healthy individuals. Of the 150 patients with probable HFMD, 55.3% (83/150) tested positive for viral isolation with presented serotypes such as EV-A71 (51.81%, 43/83), CV-A16 (32.53%, 27/83), other EVs (13.25%, 11/83), and mixed EV-A71 and CV-A16 (2.41%, 2/83). The longest duration of EV-A71 and CV-A16 shedding in stool specimens from patients with HFMD was >46 days after onset. The positive rate of EV-A71 in the stool specimens of confirmed patients dropped to 50% by the end of the third week, and the same occurred with CV-A16 by the end of approximately the seventh week after onset. Although carriers of major causative agents of HFMD in healthy populations are fewer in number, the prolonged shedding of pathogens in patients with HFMD may serve as an important factor in perpetuating and spreading HFMD epidemics.

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“…Most HFMD outbreaks have been associated with EV-A and EV-B viruses, such as CV-A6, CV-A10, CV-A4, CV-A2, CV-B4, and ECHO30 [20]. Few studies have reported CV-A2 as the main pathogen responsible for HFMD outbreaks, compared with CV-A6, CV-A10, and CV-A4 [21]. …”

Section: Discussionmentioning

confidence: 99%

Two Genotypes of Coxsackievirus A2 Associated with Hand, Foot, and Mouth Disease Circulating in China since 2008

Yang¹,

Zhang²,

Yan³

et al. 2016

PLoS ONE

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Coxsackievirus A2 (CV-A2) has been frequently detected and commonly associated with hand, foot, and mouth disease (HFMD) in China since 2008. However, limited sequences of CV-A2 are currently available. As a result, we have been focusing on the genetic characteristics of CV-A2 in the mainland of China during 2008–2015 based on national HFMD surveillance. In this study, 20 CV-A2 strains were isolated and phylogenetic analyses of the VP1 sequences were performed. Full-length genome sequences of two representative CV-A2 isolates were acquired and similarity plot and bootscanning analyses were performed. The phylogenetic dendrogram indicated that all CV-A2 strains could be divided into four genotypes (Genotypes A–D). The CV-A2 prototype strain (Fleetwood) was the sole member of genotype A. From 2008 to 2015, the CV-A2 strains isolated in China dispersed into two different genotypes (B and D). And the genotype D became the dominant circulating strains in China. Strains isolated in Russia and India from 2005 to 2011 converged into genotype C. Intertypic recombination occurred between the Chinese CV-A2 strains and other enterovirus-A donor sequences. This result reconfirmed that recombination is a common phenomenon among enteroviruses. This study helps expand the numbers of whole virus genome sequence and entire VP1 sequence of CV-A2 in the GenBank database for further researcher.

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Fourteen types of co-circulating recombinant enterovirus were associated with hand, foot, and mouth disease in children from Wenzhou, China

Cited by 45 publications

References 44 publications

Molecular Evolution and Intraclade Recombination of Enterovirus D68 during the 2014 Outbreak in the United States

Molecular Evolution and Intraclade Recombination of Enterovirus D68 during the 2014 Outbreak in the United States

Prevalence of enteroviruses in healthy populations and excretion of pathogens in patients with hand, foot, and mouth disease in a highly endemic area of southwest China

Two Genotypes of Coxsackievirus A2 Associated with Hand, Foot, and Mouth Disease Circulating in China since 2008

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