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Transcriptome analysis reveals dynamic changes in coxsackievirus A16 infected HEK 293T cells

BACKGROUND: Coxsackievirus A16 (CVA16) and enterovirus 71 (EV71) are two of the major causes of hand, foot and mouth disease (HFMD) world-wide. Although many studies have focused on infection and pathogenic mechanisms, the transcriptome profile of the host cell upon CVA16 infection is still largely...

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Autores principales: Jin, Jun, Li, Rujiao, Jiang, Chunlai, Zhang, Ruosi, Ge, Xiaomeng, Liang, Fang, Sheng, Xin, Dai, Wenwen, Chen, Meili, Wu, Jiayan, Xiao, Jingfa, Su, Weiheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5310284/
https://www.ncbi.nlm.nih.gov/pubmed/28198671
http://dx.doi.org/10.1186/s12864-016-3253-6
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author Jin, Jun
Li, Rujiao
Jiang, Chunlai
Zhang, Ruosi
Ge, Xiaomeng
Liang, Fang
Sheng, Xin
Dai, Wenwen
Chen, Meili
Wu, Jiayan
Xiao, Jingfa
Su, Weiheng
author_facet Jin, Jun
Li, Rujiao
Jiang, Chunlai
Zhang, Ruosi
Ge, Xiaomeng
Liang, Fang
Sheng, Xin
Dai, Wenwen
Chen, Meili
Wu, Jiayan
Xiao, Jingfa
Su, Weiheng
author_sort Jin, Jun
collection PubMed
description BACKGROUND: Coxsackievirus A16 (CVA16) and enterovirus 71 (EV71) are two of the major causes of hand, foot and mouth disease (HFMD) world-wide. Although many studies have focused on infection and pathogenic mechanisms, the transcriptome profile of the host cell upon CVA16 infection is still largely unknown. RESULTS: In this study, we compared the mRNA and miRNA expression profiles of human embryonic kidney 293T cells infected and non-infected with CVA16. We highlighted that the transcription of SCARB2, a cellular receptor for both CVA16 and EV71, was up-regulated by nearly 10-fold in infected cells compared to non-infected cells. The up-regulation of SCARB2 transcription induced by CVA16 may increase the possibility of subsequent infection of CVA16/EV71, resulting in the co-infection with two viruses in a single cell. This explanation would partly account for the co-circulation and genetic recombination of a great number of EV71 and CVA16 viruses. Based on correlation analysis of miRNAs and genes, we speculated that the high expression of SCARB2 is modulated by down-regulation of miRNA has-miR-3605-5p. At the same time, we found that differentially expressed miRNA target genes were mainly reflected in the extracellular membrane (ECM)-receptor interaction and circadian rhythm pathways, which may be related to clinical symptoms of patients infected with CVA16, such as aphthous ulcers, cough, myocarditis, somnolence and potentially meningoencephalitis. The miRNAs hsa-miR-149-3p and hsa-miR-5001-5p may result in up-regulation of genes in these morbigenous pathways related to CVA16 and further cause clinical symptoms. CONCLUSIONS: The present study elucidated the changes in 293T cells upon CVA16 infection at transcriptome level, containing highly up-regulated SCARB2 and genes in ECM-receptor interaction and circadian rhythm pathways, and key miRNAs in gene expression regulation. These results provided novel insight into the pathogenesis of HFMD induced by CVA16 infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-3253-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-53102842017-02-22 Transcriptome analysis reveals dynamic changes in coxsackievirus A16 infected HEK 293T cells Jin, Jun Li, Rujiao Jiang, Chunlai Zhang, Ruosi Ge, Xiaomeng Liang, Fang Sheng, Xin Dai, Wenwen Chen, Meili Wu, Jiayan Xiao, Jingfa Su, Weiheng BMC Genomics Research BACKGROUND: Coxsackievirus A16 (CVA16) and enterovirus 71 (EV71) are two of the major causes of hand, foot and mouth disease (HFMD) world-wide. Although many studies have focused on infection and pathogenic mechanisms, the transcriptome profile of the host cell upon CVA16 infection is still largely unknown. RESULTS: In this study, we compared the mRNA and miRNA expression profiles of human embryonic kidney 293T cells infected and non-infected with CVA16. We highlighted that the transcription of SCARB2, a cellular receptor for both CVA16 and EV71, was up-regulated by nearly 10-fold in infected cells compared to non-infected cells. The up-regulation of SCARB2 transcription induced by CVA16 may increase the possibility of subsequent infection of CVA16/EV71, resulting in the co-infection with two viruses in a single cell. This explanation would partly account for the co-circulation and genetic recombination of a great number of EV71 and CVA16 viruses. Based on correlation analysis of miRNAs and genes, we speculated that the high expression of SCARB2 is modulated by down-regulation of miRNA has-miR-3605-5p. At the same time, we found that differentially expressed miRNA target genes were mainly reflected in the extracellular membrane (ECM)-receptor interaction and circadian rhythm pathways, which may be related to clinical symptoms of patients infected with CVA16, such as aphthous ulcers, cough, myocarditis, somnolence and potentially meningoencephalitis. The miRNAs hsa-miR-149-3p and hsa-miR-5001-5p may result in up-regulation of genes in these morbigenous pathways related to CVA16 and further cause clinical symptoms. CONCLUSIONS: The present study elucidated the changes in 293T cells upon CVA16 infection at transcriptome level, containing highly up-regulated SCARB2 and genes in ECM-receptor interaction and circadian rhythm pathways, and key miRNAs in gene expression regulation. These results provided novel insight into the pathogenesis of HFMD induced by CVA16 infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-3253-6) contains supplementary material, which is available to authorized users. BioMed Central 2017-01-25 /pmc/articles/PMC5310284/ /pubmed/28198671 http://dx.doi.org/10.1186/s12864-016-3253-6 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Jin, Jun
Li, Rujiao
Jiang, Chunlai
Zhang, Ruosi
Ge, Xiaomeng
Liang, Fang
Sheng, Xin
Dai, Wenwen
Chen, Meili
Wu, Jiayan
Xiao, Jingfa
Su, Weiheng
Transcriptome analysis reveals dynamic changes in coxsackievirus A16 infected HEK 293T cells
title Transcriptome analysis reveals dynamic changes in coxsackievirus A16 infected HEK 293T cells
title_full Transcriptome analysis reveals dynamic changes in coxsackievirus A16 infected HEK 293T cells
title_fullStr Transcriptome analysis reveals dynamic changes in coxsackievirus A16 infected HEK 293T cells
title_full_unstemmed Transcriptome analysis reveals dynamic changes in coxsackievirus A16 infected HEK 293T cells
title_short Transcriptome analysis reveals dynamic changes in coxsackievirus A16 infected HEK 293T cells
title_sort transcriptome analysis reveals dynamic changes in coxsackievirus a16 infected hek 293t cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5310284/
https://www.ncbi.nlm.nih.gov/pubmed/28198671
http://dx.doi.org/10.1186/s12864-016-3253-6
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