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Expression of porcine Mx1 with FMDV IRES enhances the antiviral activity against foot-and-mouth disease virus in PK-15 cells

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Abstract

Foot-and-mouth disease virus (FMDV) is the most contagious pathogen in cloven-hoofed (two-toed) animals. Due to the rapid replication and spread of FMDV, novel therapeutic strategies are greatly needed to reduce or block FMDV shedding in cases of disease outbreak. Here, we generated an IRES-Mx1 construct in which the internal ribosome entry site (IRES) of FMDV was inserted between the promoter and open reading frame (ORF) of porcine myxovirus resistance protein 1 (poMx1). This construct provides more powerful protection against FMDV infection than the IRES-IFN construct that was previously generated by our group. The results indicate that this IRES-Mx1 construct was able to express poMx1 12 h after transfection and induce a robust immune response. In contrast to the control, the proliferation of virus in transfected cells was significantly inhibited, as evaluated by morphology monitoring, real-time RT-PCR, virus titration and Western blot. In addition, we also found that the antiviral activity in cells transfected with pc-IRES-Mx1 was abolished when the JAK/STAT pathway was repressed, which indicates that the antiviral mechanism of poMx1 is JAK/STAT pathway dependent. Taken together, our data suggest that the antiviral activity of poMx1 is possibly produced by affecting the host cells themselves, instead of interacting with the virus directly. The new construct reported here could be used as a novel effective therapy against FMDV infection.

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Acknowledgements

We gratefully acknowledge Prof. Qingzhen Liu (College of Life Science, Wuhan University, China) for critical review of the manuscript. We also thank Dr. Maoqing Wu (Research fellow at Harvard Medical School) of Sander International Translation LLC for manuscript polishing service. This study was supported by a grant from the National Natural Science Foundation of China (No. 31370185) and National Infrastructure of Natural Resources for Science and Technology Program (No. 2011-572).

Author contributions

YB and SC conceived and designed the experiments. YB and FH performed the experiments. YB, SC and ZCY wrote the paper. All authors have read and agreed to the final version of the manuscript.

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Authors and Affiliations

  1. State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, 430072, Hubei, China

    Bing Yuan, Hui Fang, Chao Shen & Congyi Zheng

  2. China Center for Type Culture Collection, Wuhan University, Wuhan, 430072, Hubei, China

    Chao Shen & Congyi Zheng

Authors
  1. Bing Yuan
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  2. Hui Fang
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  3. Chao Shen
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  4. Congyi Zheng
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Correspondence to Chao Shen or Congyi Zheng.

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Yuan, B., Fang, H., Shen, C. et al. Expression of porcine Mx1 with FMDV IRES enhances the antiviral activity against foot-and-mouth disease virus in PK-15 cells. Arch Virol 160, 1989–1999 (2015). https://doi.org/10.1007/s00705-015-2473-4

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  • DOI: https://doi.org/10.1007/s00705-015-2473-4

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