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Expression Profile and Function Analysis of Long Non-coding RNAs in the Infection of Coxsackievirus B3

Virologica Sinica volume 34, pages 618–630 (2019)Cite this article

Abstract

The roles of lncRNAs in the infection of enteroviruses have been barely demonstrated. In this study, we used coxsackievirus B3 (CVB3), a typical enterovirus, as a model to investigate the expression profiles and functional roles of lncRNAs in enterovirus infection. We profiled lncRNAs and mRNA expression in CVB3-infected HeLa cells by lncRNA-mRNA integrated microarrays. As a result, 700 differentially expressed lncRNAs (431 up-regulated and 269 down-regulated) and 665 differentially expressed mRNAs (299 up-regulated and 366 down-regulated) were identified in CVB3 infection. Then we performed lncRNA-mRNA integrated pathway analysis to identify potential functional impacts of the differentially expressed mRNAs, in which lncRNA-mRNA correlation network was built. According to lncRNA-mRNA correlation, we found that XLOC-001188, an lncRNA down-regulated in CVB3 infection, was negatively correlated with NFAT5 mRNA, an anti-CVB3 gene reported previously. This interaction was supported by qPCR detection following siRNA-mediated knockdown of XLOC-001188, which showed an increase of NFAT5 mRNA and a reduction of CVB3 genomic RNA. In addition, we observed that four most significantly altered lncRNAs, SNHG11, RP11-145F16.2, RP11-1023L17.1 and RP11-1021N1.2 share several common correlated genes critical for CVB3 infection, such as BRE and IRF2BP1. In all, our studies reveal the alteration of lncRNA expression in CVB3 infection and its potential influence on CVB3 replication, providing useful information for future studies of enterovirus infection.

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Abbreviations

ARRDC3:

Arrestin domain containing 3

BRE:

Brain and reproductive organ-expressed

CCRN4L:

Carbon catabolite repression 4-like

CDCA3:

Cell division cycle associated 3

CVB3:

Coxsackievirus B3

FIBP:

FGF1 intracellular binding protein

HLA-DQA1:

Major histocompatibility complex, class II, DQ alpha 1

hnRNPH3:

Heterogeneous nuclear ribonucleoprotein H3

IRF2BP1:

Insulin-like growth factor 2 mRNA-binding protein 1

KEGG:

Kyoto Encyclopedia of Genes and Genomes

LncRNA:

Long non-coding RNA

MDA5:

Melanoma differentiation associated gene 5

MTX1:

Metaxin 1

NEMF:

Nuclear export mediator factor

NFAT5:

Nuclear factor of activated T cells 5

SNHG11:

Small nucleolar RNA host gene 11

TIMP1:

TIMP metallopeptidase inhibitor 1

TMED9:

Transmembrane p24 trafficking protein 9

ZNF295:

Zinc finger protein 295

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81101234 to Lei Tong; 81571999, 81871652 to Zhaohua Zhong; 31470260 to Xingyi Ge; 81672007 to Wenran Zhao; 81772188 to Yan Wang), the Foundation of Heilongjiang Provincial Postdoctor of China (LBH-Z11076 to Lei Tong), the China Postdoctoral Science Foundation (2015M580269 to Lexun Lin), the Research Foundation of Education Bureau of Heilongjiang Province (12511176 to Lei Tong), the Hu-Xiang Youth Talents Scholar Program of Hunan Province (2017RS3017 to Xingyi Ge), Health and Family Planning Commission of Heilongjiang Province (2016-165 to Lexun Lin), the Provincial Natural Science Foundation of Hunan Province (Grant Number 2019JJ50035 to Ye Qiu) and the Fundamental Research Funds for the Central Universities of China (Grant Number 531107051162 to Ye Qiu). We are grateful to the technical support from Heilongjiang Provincial Key Laboratory of Pathogens and Immunity and Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity of Harbin Medical University. We thank Jing Li (Cnkingbio Company Ltd, Beijing, China) for technical support.

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  1. Lei Tong and Ye Qiu these authors contributed equally to this work.

Authors and Affiliations

  1. Department of Microbiology, Harbin Medical University, Harbin, 150081, China

    Lei Tong, Hui Wang, Yunyue Qu, Lexun Lin, Weizhen Xu & Zhaohua Zhong

  2. College of Biology, Hunan University, Changsha, 410012, China

    Ye Qiu, Yuanbo Zhao, Hongyan He & Xingyi Ge

  3. Department of Cell Biology, Harbin Medical University, Harbin, 150081, China

    Yan Wang & Wenran Zhao

  4. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, V6Z 1Y6, Canada

    Guangze Zhao, Mary H. Zhang & Decheng Yang

Authors
  1. Lei Tong
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  2. Ye Qiu
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  3. Hui Wang
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  4. Yunyue Qu
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  5. Yuanbo Zhao
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  6. Lexun Lin
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  7. Yan Wang
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  8. Weizhen Xu
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  9. Wenran Zhao
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  11. Guangze Zhao
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  13. Decheng Yang
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  14. Xingyi Ge
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  15. Zhaohua Zhong
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Contributions

LT, YQ, XG and ZZ designed the experiments. HW, YQ, LL, YW, WX, WZ and HH carried out the experiments. LT, YQ, YZ, GZ, MHZ and DY analyzed the data. YQ wrote the paper. LT, YQ, DY, XG and ZZ checked and finalized the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Xingyi Ge or Zhaohua Zhong.

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The authors declare that they have no conflict of interest.

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

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Tong, L., Qiu, Y., Wang, H. et al. Expression Profile and Function Analysis of Long Non-coding RNAs in the Infection of Coxsackievirus B3. Virol. Sin. 34, 618–630 (2019). https://doi.org/10.1007/s12250-019-00152-x

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  • DOI: https://doi.org/10.1007/s12250-019-00152-x

Keywords

  • Coxsackievirus B3 (CVB3)
  • lncRNA-mRNA correlation network
  • Long non-coding RNA (lncRNA)
  • XLOC-001188
  • NFAT5