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Transcriptomic analysis reveals that coxsackievirus B3 Woodruff and GD strains use similar key genes to induce FoxO signaling pathway activation in HeLa cells

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Abstract

Coxsackievirus B3 (CVB3) is a major cause of viral myocarditis in humans. Although there have been studies on CVB3 infection and pathogenesis, the precise disease mechanism is still not clear. In this study, we used RNA-seq technology to compare the transcriptomic profile of virus-infected HeLa cells to that of uninfected cells to identify key genes involved in host-virus interaction. For this, two CVB3 strains, CVB3 Woodruff, an experimental strain, and GD16-69/GD/CHN/2016, a clinical strain, were selected to examine the common mechanisms underlying their infection. Transcriptomic profiles revealed increased expression of the cell cycle genes CCNG2, GADD45B, PIM1, RBM15, KLF10, and RIOK3 and decreased expression of CYBA. The autophagy-related genes ATG12 and YOD1 were found to be upregulated, while the expression of SOD2 and XPO1 increased slightly in infected cells, and only a minor change was observed in GABARAP expression. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed the FoxO signaling pathway to be enriched and showed a close interaction with differentially expressed genes (DEGs) in the protein-protein interaction network. DEGs associated with related pathways such as cell cycle, autophagy, and oxidative stress resistance were also confirmed by qRT-PCR. In summary, the FoxO signaling pathway was activated during infection with both CVB3 strains and was found to have a regulatory role in downstream pathways such as cell cycle, autophagy, oxidative stress resistance, and the antiviral immune response.

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Acknowledgements

We appreciate the kind support from Wenbo Xu, Director of the National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, for the resources and information on CVB3 epidemic viral strains.

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This article was not supported by any particular grant.

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Authors and Affiliations

  1. State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Rd, Beijing, 102206, China

    Mi Liu & Jun Han

  2. WHO WPRO Regional Polio Reference Laboratory, National Health Commission Key Laboratory for Medical Virology, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Road, Beijing, 102206, China

    Qian Yang

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  1. Mi Liu
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Contributions

M.L. and J.H. conceived and designed the experiments and revised the manuscript. M.L. performed the experiments, analyzed the data, and wrote the manuscript. Q.Y. contributed reagents and materials. As the corresponding author of this study, J.H. has access to all of the data from the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Correspondence to Jun Han.

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Liu, M., Yang, Q. & Han, J. Transcriptomic analysis reveals that coxsackievirus B3 Woodruff and GD strains use similar key genes to induce FoxO signaling pathway activation in HeLa cells. Arch Virol 167, 131–140 (2022). https://doi.org/10.1007/s00705-021-05292-8

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  • DOI: https://doi.org/10.1007/s00705-021-05292-8

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