Molecular characterization of Coxsackievirus A16 strains isolated from children with severe hand, foot, and mouth disease in Yunnan, Southwest China, during 2009‐2015

Zhang, Ming; Zhao, Yilin; Zhang, Haihao; Lin, Keqin; Liu, Hongbo; Zhang, Jie; Ding, Lisha; Huang, Xintian; Yang, Zhaoqing; Ma, Shaohui

doi:10.1002/jmv.25297

Cited by 9 publications

(5 citation statements)

References 24 publications

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“…Zhao et al used worldwide data (sampled during 1951-2013) for analysis and found the mean evolutionary rate of CVA16 was 6.656 × 10 -3 substitutions/site/year [41]. In this study, the mean evolutionary rate of CVA16 circulating in Beijing from 2010 to 2019 was 4.49 × 10 -3 substitutions/site/year, which is similar to that in Yunnan Province, China from 2009 to 2015 (4.545 × 10 -3 substitutions/site/year) and France from 2010 to (4.5 × 10 -3 substitutions/site/year) [13,39].…”

Section: Discussionsupporting

confidence: 70%

“…B1b, the complex recombinant of CVA16 with CVA4 and EV-A71, co-circulated with B1a in China during 1999-2008 [37,38]. After 2010, B1b became the predominant strain in China [12,39,40]. Clade B1c strain was first emerged in Malaysia (2005Malaysia ( -2007, then detected in several countries, such as Russia, France, Indian and Japan, and induced an outbreak of HFMD in Indian in 2013 [34,41,42].…”

Section: Discussionmentioning

confidence: 99%

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Molecular epidemiology of coxsackievirus A16 circulating in children in Beijing, China from 2010 to 2019

Jia

et al. 2021

World J Pediatr

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Background Coxsackievirus A16 (CVA16) is one of the major etiological agents of hand, foot and mouth disease (HFMD). This study aimed to investigate the molecular epidemiology and evolutionary characteristics of CVA16. Methods Throat swabs were collected from children with HFMD and suspected HFMD during 2010–2019. Enteroviruses (EVs) were detected and typed by real-time reverse transcription-polymerase chain reaction (RT-PCR) and RT-PCR. The genotype, evolutionary rate, the most recent common ancestor, population dynamics and selection pressure of CVA16 were analyzed based on viral protein gene (VP1) by bioinformatics software. Results A total of 4709 throat swabs were screened. EVs were detected in 3180 samples and 814 were CVA16 positive. More than 81% of CVA16-positive children were under 5 years old. The prevalence of CVA16 showed obvious periodic fluctuations with a high level during 2010–2012 followed by an apparent decline during 2013–2017. However, the activities of CVA16 increased gradually during 2018–2019. All the Beijing CVA16 strains belonged to sub-genotype B1, and B1b was the dominant strain. One B1c strain was detected in Beijing for the first time in 2016. The estimated mean evolutionary rate of VP1 gene was 4.49 × 10–3 substitution/site/year. Methionine gradually fixed at site-23 of VP1 since 2012. Two sites were detected under episodic positive selection, one of which (site-223) located in neutralizing linear epitope PEP71. Conclusions The dominant strains of CVA16 belonged to clade B1b and evolved in a fast evolutionary rate during 2010–2019 in Beijing. To provide more favorable data for HFMD prevention and control, it is necessary to keep attention on molecular epidemiological and evolutionary characteristics of CVA16.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Molecular epidemiology of coxsackievirus A16 circulating in children in Beijing, China from 2010 to 2019

Jia

et al. 2021

World J Pediatr

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“…The information for CVA6, CVA16 and CVA10 strains with known disease background was obtained from previous reports [4,5,7,27,30,[34][35][36][37][38][39][40] and from the GenBank database. The following nearly complete genome sequences were obtained from GenBank: five CVA6 strains associated with severe HFMD and 28 CVA6 strains associated with mild HFMD; 23 CVA16 strains associated with severe HFMD and 20 CVA16 strains associated with mild HFMD; five CVA10 strains associated with severe HFMD and 26 CVA10 strains associated with mild HFMD.…”

Section: Comparative Genomic Analysis Of Strains Associated With Severe and Mild Hfmdmentioning

confidence: 99%

Molecular epidemiology of enteroviruses associated with severe hand, foot and mouth disease in Shenzhen, China, 2014-2018

Chen

Yang

et al. 2020

Arch Virol

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In this study, we investigated the epidemiology and molecular characteristics of enteroviruses associated with severe hand, foot and mouth disease (HFMD) in Shenzhen, China, during 2014-2018. A total of 137 fecal specimens from patients with severe HFMD were collected. Enterovirus (EV) types were determined using real-time reverse transcription polymerase chain reaction (RT-PCR), RT nested PCR, and sequencing. Sequences were analyzed using bioinformatics programs. Of 137 specimens tested, 97 (70.8%), 12 (8.8%), and 10 (7.3%) were positive for EV-A71, coxsackievirus A6 (CVA6), and CVA16, respectively. Other pathogens detected included CVA2 (2.9%, 4/137), CVA10 (2.9%, 4/137), CVA5 (0.7%, 1/137), echovirus 6 (E6) (0.7%, 1/137) and E18 (0.7%, 1/137). The most frequent complication in patients with proven EV infections was myoclonic jerk, followed by aseptic encephalitis, tachypnea, and vomiting. The frequencies of vomiting and abnormal eye movements were higher in EV-A71-infected patients than that in CVA6-infected or CVA16-infected patients. Molecular phylogeny based on the complete VP1 gene revealed no association between the subgenotype of the virus and disease severity. Nevertheless, 12 significant mutations that were likely to be associated with virulence or the clinical phenotype were observed in the 5’UTR, 2A pro , 2C, 3A, 3D pol and 3’UTR of CVA6. Eight significant mutations were observed in the 5’UTR, 2B, 3A, 3D pol and 3’UTR of CVA16, and 10 significant mutations were observed in the 5’UTR, VP1, 3A and 3C pro of CVA10. In conclusion, EV-A71 is still the main pathogen causing severe HFMD, although other EV types can also cause severe complications. Potential virulence or phenotype-associated sites were identified in the genomes of CVA6, CVA16, and CVA10. Electronic supplementary material The online version of this article (10.1007/s00705-020-04734-z) contains supplementary material, which is available to authorized users.

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“…BEAST analysis showed that E33 had an average nucleotide substitution rate of 1.11 × 10 −2 in VP1 region, which was faster than EV-A71 (4-7 × 10 −3 ) [35], CVA16 (4.545 × 10 −3 ) [36], CVA6 (4.10 × 10 −3 ) [37], CVA10 (5.5-14.1×10 −3 ) [38], and CVA9 (3.27 × 10 −3 ) [39]. This result is consistent with the study by Lukashev et al on the nucleotide replacement rate of non-poliovirus [40].…”

Section: Discussionmentioning

confidence: 96%

Molecular Characteristics and Genetic Evolution of Echovirus 33 in Mainland of China

et al. 2022

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Echovirus, a member of the Enterovirus B (EV-B) family, has led to numerous outbreaks and pandemics, causing a broad spectrum of diseases. Based on the national hand, foot, and mouth disease (HFMD) surveillance system, seven strains of echovirus 33 (E33) were isolated from Mainland of China between 2010 and 2018. The whole genomes of these strains were isolated and sequenced, and phylogenetic trees were constructed based on the gene sequences in different regions of the EV-B prototype strains. It was found that E33 may be recombined in the P2 and P3 regions. Five genotypes (A–E) were defined based on the entire VP1 region of E33, of which the C gene subtype was the dominant gene subtype at present. Recombinant analysis showed that genotype C strains likely recombined with EV-B80, EV-B85, E13, and CVA9 in the P2 and P3 regions, while genotype E had the possibility of recombination with CVB3, E3, E6, and E4. Results of Bayesian analysis indicated that E33 may have appeared around 1955 (95% confidence interval: 1945–1959), with a high evolutionary rate of 1.11 × 10−2 substitution/site/year (95% highest posterior density (HPD): 8.17 × 10−3 to 1.4 × 10−2 substitution/site/year). According to spatial transmission route analysis, two significant transmission routes were identified: from Australia to India and from Oman to Thailand, which the E33 strain in Mainland of China likely introduced from Mexico and India. In conclusion, our study fills the gaps in the evolutionary analysis of E33 and can provide important data for enterovirus surveillance.

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Molecular characterization of Coxsackievirus A16 strains isolated from children with severe hand, foot, and mouth disease in Yunnan, Southwest China, during 2009‐2015

Cited by 9 publications

References 24 publications

Molecular epidemiology of coxsackievirus A16 circulating in children in Beijing, China from 2010 to 2019

Molecular epidemiology of coxsackievirus A16 circulating in children in Beijing, China from 2010 to 2019

Molecular epidemiology of enteroviruses associated with severe hand, foot and mouth disease in Shenzhen, China, 2014-2018

Molecular Characteristics and Genetic Evolution of Echovirus 33 in Mainland of China

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