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Molecular surveillance of coxsackievirus A16 reveals the emergence of a new clade in mainland China

  • Long ChenEmail author
  • Xiang-Jie Yao
  • Shao-Jian Xu
  • Hong Yang
  • Chun-Li Wu
  • Jing Lu
  • Wen-Bo Xu
  • Hai-Long Zhang
  • Jun Meng
  • Yong Zhang
  • Ya-Qing HeEmail author
  • Ren-Li ZhangEmail author
Annotated Sequence Record
  • 55 Downloads

Abstract

Coxsackievirus A16 (CV-A16) of the genotypes B1a and B1b have co-circulated in mainland China in the past decades. From 2013 to 2017, a total of 3,008 specimens from 3,008 patients with mild hand, foot, and mouth disease were collected in the present study. Viral RNA was tested for CV-A16 by a real-time RT-PCR method, and complete VP1 sequences and full-length genome sequences of CV-A16 strains from this study were determined by RT-PCR and sequencing. Sequences were analyzed using a series of bioinformatics programs. The detection rate for CV-A16 was 4.1%, 25.9%, 10.6%, 28.1% and 12.9% in 2013, 2014, 2015, 2016 and 2017, respectively. Overall, the detection rate for CV-A16 was 16.5% (497/3008) in this 5-year period in Shenzhen, China. One hundred forty-two (142/155, 91.6%) of the 155 genotype B1 strains in the study belonged to subgenotype B1b, and 13 (13/155, 8.4%) strains belonged to subgenotype B1a. Two strains (CVA16/Shenzhen174/CHN/2017 and CVA16/Shenzhen189/CHN/2017) could not be assigned to a known genotype. Phylogenetic analysis of these two strains and other Chinese CV-A16 strains indicated that these two CV-A16 strains clustered independently in a novel clade whose members differed by 8.4%-11.8%, 8.4%-12.1%, and 14.6%-14.8% in their nucleotide sequences from those of Chinese B1a, B1b, and genotype D strains, respectively. Phylogenetic analysis of global CV-A16 strains further indicated that the two novel CV-A16 strains from this study grouped in a previously uncharacterized clade, which was designated as the subgenogroup B3 in present study. Meanwhile, phylogenetic reconstruction revealed two other new genotypes, B1d and B4, which included a Malaysian strain and two American strains, respectively. The complete genome sequences of the two novel CV-A16 strains showed the highest nucleotide sequence identity of 92.3% to the Malaysian strain PM-15765-00 from 2000. Comparative analysis of amino acid sequences of the two novel CV-A16 strains and their relatives suggested that variations in the nonstructural proteins may play an important role in the evolution of modern CV-A16.

Notes

Acknowledgements

This work was supported by the Sanming Project of Medicine in Shenzhen (No. SZSM201611064), the Shenzhen Science and Technology Research Project (JCYJ20170306160217433), and special funds for the surveillance of HFMD from Shenzhen CDC. We are grateful to the pediatricians from the sentinel surveillance system for HFMD in Shenzhen, China.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Animal and human rights statement

This article does not contain any studies with human or animal subjects performed by any of the authors.

Supplementary material

705_2018_4112_MOESM1_ESM.docx (43 kb)
Supplementary material 1 (DOCX 43 kb)

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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Major Infectious Disease Control Key Laboratory and Shenzhen Public Service Platform of Pathogenic Microorganisms RepositoryInstitute of Pathogen Biology, Shenzhen Center for Disease Control and PreventionShenzhenChina
  2. 2.District Key Laboratory for Infectious Disease Prevention and ControlLonghua Center for Disease Control and PreventionShenzhenChina
  3. 3.Guangdong Provincial Institution of Public Health, Guangdong Provincial Center for Disease Control and PreventionGuangzhouChina
  4. 4.National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and PreventionBeijingChina

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