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Transcriptomic analysis of cells in response to EV71 infection and 2Apro as a trigger for apoptosis via TXNIP gene

  • Chenguang Yao
  • Kanghong Hu
  • Caili Xi
  • Ni Li
  • Yanhong WeiEmail author
Research Article

Abstract

Background

Enterovirus 71 (EV71) is the main pathogen of hand-foot-mouth disease (HFMD) and sometimes causes several neurological complications. However, the underlying mechanism of the host response to the virus infection remains unclear.

Objective

To reveal the cell-specific transcriptional response of cultured RD cells following infection with EV71, and better understand the molecular mechanisms of virus-host interactions.

Methods

The RD cells were infected with or without EV71 for 24 h, and then transcriptome sequencing and qRT-PCR were performed to analyze the transcriptome difference of functional genes.

Results

More than 15000 genes were identified in transcriptome sequencing. In comparison with uninfected RD cells, 329 DEGs were identified in cells infected with EV71. GO and KEGG pathway enrichment analysis showed that most of the DEGs were related to DNA binding, transcriptional regulation, immune response and inflammatory response, apoptosis inducing factors and enriched in JAK-STAT and MAPK signaling pathways. TXNIP (thioredoxin-interacting protein) gene was further demonstrated to play an important role participating in cellular apoptosis induced by EV71, and the apoptosis and death mediated by TXNIP during EV71 infection was triggered by viral 2A protease (2Apro), not 3C protease (3Cpro).

Conclusion

Our study demonstrated that RD cells have a significant response to EV71 infection, including immune response and apoptosis. 2Apro might be a key inducer relative to the cellular apoptosis and death mediated by TXNIP during EV71 infection. These data would contribute to preferably understand the process at the molecular level and provide theoretical foundation for diagnosis and treatment of EV71-related diseases.

Keywords

Enterovirus 71 (EV71) RNA-Seq analysis Apoptosis TXNIP (thioredoxin-interacting protein) 2A protease (2Apro

Notes

Acknowledgements

This work received financial support from the National Natural Science Foundation of China (31400153, to WYH), the Collaborative Grant-in-Aid of the HBUT National “111” Center for Cellular Regulation and Molecular Pharmaceutics (XBTK-2018005, to WYH), and the Doctoral Scientific Research Foundation of Hubei University of Technology (BSQD2015004, to WYH).

Author contributions

Conceived the idea and initiated the work: WYH, YCG, & HKH. Contributed to design of experiments: WYH, HKH, YCG, & XCL. Performed the experiments: YCG, HKH, XCL & LN. Contributed reagents/materials/analysis tools: WYH, XCL, & LN. Analysis of experiments and results: WYH, YCG, & HKH. Contribution in generating graphics: YCG, & HKH. Writing of the manuscript: YCG & WYH. All the authors read and approved the manuscript.

Compliance with ethical standards

Conflict of interest

All authors Chenguang Yao, Kanghong Hu, Caili Xi, Ni Li and Yanhong Wei declare that they have no conflict of interest.

Research involving human participants and/or animals

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

Supplementary material

13258_2018_760_MOESM1_ESM.xls (204 kb)
Table S1. GO enrichment and KEGG pathway analysis for 329 DEGs. All the DEGs were differentially expressed, with p < 0.05, fold change (log2ratio) > 1. The fold change for each gene was expressed as the ratio of expression between the two populations, infected RD cells with EV71 and uninfected RD cells. GO enrichment and KEGG pathway analysis were performed by DAVID online tool. (Excel) (XLS 204 KB)
13258_2018_760_MOESM2_ESM.xls (28 kb)
Table S2. GO enrichment and KEGG pathway analysis for up-regulated genes (p < 0.05). (Excel) (XLS 27 KB)
13258_2018_760_MOESM3_ESM.xls (28 kb)
Table S3. GO enrichment and KEGG pathway analysis for down-regulated genes (p < 0.05). (Excel) (XLS 28 KB)

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Copyright information

© The Genetics Society of Korea and Springer Nature B.V. 2018

Authors and Affiliations

  • Chenguang Yao
    • 1
  • Kanghong Hu
    • 1
  • Caili Xi
    • 1
  • Ni Li
    • 1
  • Yanhong Wei
    • 1
    Email author
  1. 1.National “111” Center for Cellular Regulation and Molecular Pharmaceutics, Hubei Key Laboratory of Industrial Microbiology, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, Sino-German Biomedical CenterHubei University of TechnologyWuhanChina

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