title: Transcriptome analysis reveals dynamic changes in coxsackievirus A16 infected HEK 293T cells.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, 130012, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Jin
authors.affiliation: BIG Data Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Rujiao
authors.initials: R
authors.lastname: Li
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, 130012, China.|Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, School of Life Sciences, Jilin University, Changchun, 130012, China.
authors.forename: Chunlai
authors.initials: C
authors.lastname: Jiang
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Ruosi
authors.initials: R
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Ge
authors.affiliation: BIG Data Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liang
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Sheng
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, 130012, China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Dai
authors.affiliation: BIG Data Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Meili
authors.initials: M
authors.lastname: Chen
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Jiayan
authors.initials: J
authors.lastname: Wu
authors.affiliation: BIG Data Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China. xiaojf@big.ac.cn.|CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China. xiaojf@big.ac.cn.
authors.forename: Jingfa
authors.initials: J
authors.lastname: Xiao
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, 130012, China. suweiheng@jlu.edu.cn.|Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, School of Life Sciences, Jilin University, Changchun, 130012, China. suweiheng@jlu.edu.cn.
authors.forename: Weiheng
authors.initials: W
authors.lastname: Su
mesh_terms: D002478:Cells, Cultured; D016000:Cluster Analysis; D004770:Enterovirus / Q000502:physiology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D057809:HEK293 Cells; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D051907:Lysosomal Membrane Proteins / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051116:Receptors, Scavenger / Q000235:genetics; D059467:Transcriptome
chemical_list: D051907:Lysosomal Membrane Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D051116:Receptors, Scavenger; C074299:SCARB2 protein, human
keywords: Coxsackievirus A16; Gene expression and regulation; Hand, foot and mouth disease; RNA-seq; SCARB2; miRNA-seq