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Clinical and molecular epidemiologic features of enterovirus D68 infection in children with acute lower respiratory tract infection in China

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Abstract

Acute flaccid paralysis (AFP) associated with enterovirus D68 (EV-D68) infection has attracted much attention since an outbreak in the USA in 2014. Notably, EV-D68 was detected in a child with AFP for the first time in China in 2018. In a multicentre study from May 2017 to December 2019, we monitored EV-D68 infections in hospitalized children with acute lower respiratory tract infection (ALRTI) in China. Out of 3,071 samples collected from patients with ALRTI, ten were positive for EV-D68. All patients presented with mild diseases with no neurological symptoms or signs. Phylogenetic analysis based on the VP1 gene showed that all EV-D68 sequences obtained in this study belonged to subclade B3 and were close to sequences of EV-D68 strains obtained from patients with AFP in the USA. Four EV-D68 strains were isolated, and their complete genome sequences were determined. These sequences did not show any evidence of recombination events. To assess their neurotropism, the isolates were used to infect the “neuronal-like” cell line SH-SY5Y, and resulted in a cytopathic effect. We further analysed the structure and sites that may be associated with neurovirulence, including the stem-loop structure in the untranslated region (3’UTR) and identified amino acid substitutions (M291T, V341A, T860N, D927N, S1108G, and R2005K) in the coding region and specific nucleotides (127T, 262C, and 339T) in the 5' UTR. In conclusion, EV-D68 infection was detected in a small number of children with ALRTI in China from 2017 to 2019. Disease symptoms in these children were relatively mild with no neurological complications, and all EV-D68 sequences belonged to subclade B3.

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Data availability

All sequences are available on the NCBI website (MZ824215–MZ824224).

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Acknowledgements

We thank all the contributors.

Funding

This work was supported by the National Natural Science Foundation of China (Grant number 81971922), the Beijing Natural Science Foundation (Grant number L192014), National Science and Technology Major Projects (Grant number 2017ZX10104001-005-010, 2017ZX10103004-004), and the CAMS Innovation Fund for Medical Sciences (CIFMS) (Grant number 2019–I2M–5–026).

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Author notes

  1. Qi Li and Xiangpeng Chen contributed equally to this work.

Authors and Affiliations

  1. Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, Research Unit of Critical Infection in Children, Chinese Academy of Medical Sciences, 2019RU016, Laboratory of Infection and Virology, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, China

    Qi Li, Xiangpeng Chen, Junhong Ai, Yun Zhu, Ran Wang, Yali Duan, Meng Zhang & Zhengde Xie

  2. Yinchuan Maternal and Child Health Care Hospital, Yinchuan, 750001, China

    Lei Li

  3. The 2nd Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, 325027, China

    Changchong Li

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Contributions

QL, XC, and ZX proposed and designed this research. QL, JA, YZ, RW, YD, and MZ performed the detection experiments. QL and XC organized and analysed the data. QL wrote the manuscript and made the figures and tables. ZX and XC checked and finalized the manuscript. LL and CL provided clinical sample resources. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Zhengde Xie.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study was approved by the Medical Ethics Committee of Beijing Children’s Hospital, Capital Medical University (No. 2017-k-15).

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Handling Editor: Diego G. Diel.

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Supplementary Information

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705_2023_5823_MOESM1_ESM.pdf

Supplementary file1 Supplementary Fig. S1 The phylogenetic trees of (A)VP4, (B)VP2, (C)VP3, (D)2A, (E)2B, (F)2C, (G)3A, (H)3B, (I)3C and (J)3D constructed using 13 sequences from various clades or subclades of EV-D68, one from EV-D70, one from EV-D111, one from EV-D120, and one from EV-D210. Only VP4 and VP1 sequences were available for EV-D120. The phylogenetic trees were generated using the neighbor-joining method based on the Tajima–Nei model with 1000 replicates. The red dots indicate the strains obtained in this study. The black triangle indicates the EV-D68 prototype strain (accession number NC038308) (PDF 7782 KB)

Supplementary file2 (DOCX 25 KB)

Supplementary file3 (DOCX 30 KB)

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Li, Q., Chen, X., Ai, J. et al. Clinical and molecular epidemiologic features of enterovirus D68 infection in children with acute lower respiratory tract infection in China. Arch Virol 168, 206 (2023). https://doi.org/10.1007/s00705-023-05823-5

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