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In vitro and in vivo protection against enterovirus 71 by an antisense phosphorothioate oligonucleotide

Archives of Virology volume 159, pages 2339–2347 (2014)Cite this article

Abstract

Enterovirus 71 (EV71) is a highly infectious virus that is a major cause of hand, foot, and mouth disease (HFMD), which can lead to severe neurological complications. Currently, there is no effective therapy against EV71. Five antisense oligodeoxynucleotides targeting the 5′-terminal conserved domain of the viral genome were designed using a method based on multiple predicted target mRNA structures. They were then screened for anti-EV71 activity in vitro based on their ability to inhibit an EV71-induced cytopathic effect (CPE). A novel antisense oligonucleotide (EV5) was tested both in rhabdomyosarcoma (RD) cells and in vivo using a mouse model, with a random oligonucleotide (EV5R) of EV5 as a control. EV5 was identified as having significant anti-EV71 activity in vitro and in vivo without significant cytotoxicity. Treatment of RD and Vero cells with antisense oligodeoxynucleotide EV5 significantly and specifically alleviated the cytopathic effect of EV71 in vitro. The inhibitory effect was dose dependent and specific, with a corresponding decrease in viral RNA and viral protein levels. In vivo, EV5 was specifically effective against EV71 virus in preventing death, decreasing weight reduction and reducing the viral RNA copy number and the level of viral proteins in the lungs, intestines and muscles. These results demonstrate the potential and feasibility of using antisense oligodeoxynucleotides specific for the 5′-terminal conserved domain of the viral genome as an antiviral therapy for EV71 disease.

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Acknowledgements

This work was supported by a grant from the National Natural Science Foundation of China (no. 31270197) and two grants from the National Science and Technology Major Projects (no. 2013ZX09-304-102 and 2014ZX09-304-313).

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Affiliations

  1. Beijing Institute of Radiation Medicine, Beijing Key Laboratory of New Molecular Diagnosis Technologies for Infectious Diseases, 27 Taiping Road, Haidian District, Beijing, 100850, People’s Republic of China

    Juan Liu, Zhe Zhou, Kang Li, Mingming Han, Jing Yang & Shengqi Wang

  2. Henan University of Traditional Chinese Medicine, Zhengzhou, 450008, People’s Republic of China

    Shengqi Wang

  3. Beijing University of Technology, Beijing, 100124, People’s Republic of China

    Juan Liu & Kang Li

Authors
  1. Juan Liu
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  2. Zhe Zhou
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  3. Kang Li
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  4. Mingming Han
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  5. Jing Yang
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  6. Shengqi Wang
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Correspondence to Jing Yang or Shengqi Wang.

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J. Liu and Z. Zhou contributed equally to the work.

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Liu, J., Zhou, Z., Li, K. et al. In vitro and in vivo protection against enterovirus 71 by an antisense phosphorothioate oligonucleotide. Arch Virol 159, 2339–2347 (2014). https://doi.org/10.1007/s00705-014-2054-y

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  • DOI: https://doi.org/10.1007/s00705-014-2054-y

Keywords

  • Antiviral Activity
  • West Nile Virus
  • Vero Cell
  • EV71 Infection
  • Mipomersen