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Genome analysis of enterovirus 71 strains differing in mouse pathogenicity

Abstract

Enterovirus 71 (EV71) is a major causative agent of hand, foot, and mouth disease (HFMD) and is occasionally associated with severe neurological diseases. The investigation of virulence determinants of EV71 is rudimentary. Therefore, it is important to understand the relationship between EV71 virulence and genomic information. In this study, a series of analyses about full-length genomic sequence were performed on six EV71 strains isolated from HFMD patients with either severe or mild clinical symptoms. A one-day-old BALB/c mouse model was used to study the infection characteristics. Results showed all six strains were of the subgenogroup C4a. Viral full-length genomic sequence analysis showed that a total of 40 nucleotide differences between strains of highly and low virulence were revealed. Among all mutations, three nucleotide mutations were found in the untranslated region. A mutation, nt115, at internal ribozyme entry site (IRES) caused RNA secondary structural change. The other 37 mutations were all located in the open reading frame resulting in 8 amino acid mutations. Importantly, we discovered that a mutation of amino acid (Asn1617 → Asp1617) in the 3C proteinase (3Cpro) of highly and low pathogenic strains could lead to conformational change at the active center, suggesting that this site may be a virulence determinant of EV71.

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Acknowledgments

We thank Prof. Zhongtao Gai and Dr. Ying Zhang (Jinan Infectious Diseases Hospital, China) for providing fecal samples of HFMD patients. This work was supported by the Intramural Institutional of Basic Medicine Grant (2014-2), Shandong Academy of Medical Sciences Grant (2014-11), the Department of Health and Family-plan Bureau (2014WS0068), Shandong Provincial College of traditional Chinese medicine antiviral Collaborative Innovation Center (XTCX2014), the national science and technology major special project of China (2014ZX09509-001001008), the Natural Science Foundation of Shandong Province (ZR2011HQ030 and ZR2013HQ039), and the National Natural Science Foundation of China (NSFC31500050).

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Correspondence to Liguo An or Lizeng Qin.

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The authors declare no conflict of interest.

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Edited by Zhen F. Fu.

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Li, P., Yue, Y., Song, N. et al. Genome analysis of enterovirus 71 strains differing in mouse pathogenicity. Virus Genes 52, 161–171 (2016). https://doi.org/10.1007/s11262-015-1271-0

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Keywords

  • Genome
  • Enterovirus 71 (EV71)
  • Mutation
  • Virulence
  • 3C proteinase (3Cpro)