Identification of microRNAs Involved in the Host Response to Enterovirus 71 Infection by a Deep Sequencing Approach

Role of microRNA (miRNA) has been highlighted in pathogen-host interactions recently. To identify cellular miRNAs involved in the host response to enterovirus 71 (EV71) infection, we performed a comprehensive miRNA profiling in EV71-infected Hep2 cells through deep sequencing. 64 miRNAs were found whose expression levels changed for more than 2-fold in response to EV71 infection. Gene ontology analysis revealed that many of these mRNAs play roles in neurological process, immune response, and cell death pathways, which are known to be associated with the extreme virulence of EV71. To our knowledge, this is the first study on host miRNAs expression alteration response to EV71 infection. Our findings supported the hypothesis that certain miRNAs might be essential in the host-pathogen interactions.

[1]  Sandra B. Munro,et al.  Detection of Cancer with Serum miRNAs on an Oligonucleotide Microarray , 2009, PloS one.

[2]  Takaji Wakita,et al.  Systematic identification of microRNA and messenger RNA profiles in hepatitis C virus-infected human hepatoma cells. , 2010, Virology.

[3]  Thomas D. Schmittgen,et al.  Analyzing real-time PCR data by the comparative CT method , 2008, Nature Protocols.

[4]  P. Sarnow,et al.  Modulation of Hepatitis C Virus RNA Abundance by a Liver-Specific MicroRNA , 2005, Science.

[5]  P. Tang,et al.  Reticulon 3 Binds the 2C Protein of Enterovirus 71 and Is Required for Viral Replication* , 2007, Journal of Biological Chemistry.

[6]  V. Moulton,et al.  Deep sequencing of tomato short RNAs identifies microRNAs targeting genes involved in fruit ripening. , 2008, Genome research.

[7]  M. G. Koerkamp,et al.  Dynamics of gene expression revealed by comparison of serial analysis of gene expression transcript profiles from yeast grown on two different carbon sources. , 1999, Molecular biology of the cell.

[8]  Jialing Huang,et al.  Cellular microRNAs contribute to HIV-1 latency in resting primary CD4+ T lymphocytes , 2007, Nature Medicine.

[9]  L. Lim,et al.  MicroRNA targeting specificity in mammals: determinants beyond seed pairing. , 2007, Molecular cell.

[10]  F. Hayden,et al.  Picornavirus infections: a primer for the practitioner. , 2000, Archives of family medicine.

[11]  Anton J. Enright,et al.  Identification of Virus-Encoded MicroRNAs , 2004, Science.

[12]  P. McMinn,et al.  Neurological manifestations of enterovirus 71 infection in children during an outbreak of hand, foot, and mouth disease in Western Australia. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[13]  P. Spear,et al.  Disruption of Adherens Junctions Liberates Nectin-1 To Serve as Receptor for Herpes Simplex Virus and Pseudorabies Virus Entry , 2002, Journal of Virology.

[14]  T. Yeh,et al.  Neurologic complications in children with enterovirus 71 infection. , 1999, The New England journal of medicine.

[15]  S. Lou,et al.  Whole genome expression profiling of hepatitis B virus-transfected cell line reveals the potential targets of anti-HBV drugs , 2008, The Pharmacogenomics Journal.

[16]  F. Slack,et al.  Epstein-Barr virus-mediated dysregulation of human microRNA expression , 2008, Cell cycle.

[17]  C. Burge,et al.  Most mammalian mRNAs are conserved targets of microRNAs. , 2008, Genome research.

[18]  S. Gau,et al.  Neurodevelopment and cognition in children after enterovirus 71 infection. , 2007, The New England journal of medicine.

[19]  K. Livak,et al.  Real-time quantification of microRNAs by stem–loop RT–PCR , 2005, Nucleic acids research.

[20]  V. Ambros,et al.  Role of MicroRNAs in Plant and Animal Development , 2003, Science.

[21]  C. Croce,et al.  An oligonucleotide microchip for genome-wide microRNA profiling in human and mouse tissues. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[22]  M. Figlerowicz,et al.  Human- and virus-encoded microRNAs as potential targets of antiviral therapy. , 2009, Mini reviews in medicinal chemistry.

[23]  L. Goff,et al.  Ago2 Immunoprecipitation Identifies Predicted MicroRNAs in Human Embryonic Stem Cells and Neural Precursors , 2009, PloS one.

[24]  H. Ning,et al.  Comparison of enterovirus 71 and coxsackie-virus A16 clinical illnesses during the Taiwan enterovirus epidemic, 1998. , 1999, The Pediatric infectious disease journal.

[25]  C. Burge,et al.  Conserved Seed Pairing, Often Flanked by Adenosines, Indicates that Thousands of Human Genes are MicroRNA Targets , 2005, Cell.

[26]  Brian S. Roberts,et al.  The colorectal microRNAome. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[27]  Robert J. Moore,et al.  A microRNA catalog of the developing chicken embryo identified by a deep sequencing approach. , 2008, Genome research.

[28]  Nectarios Koziris,et al.  DIANA-microT web server: elucidating microRNA functions through target prediction , 2009, Nucleic Acids Res..

[29]  V. Stollar,et al.  Identification of genes involved in the host response to enterovirus 71 infection , 2011, Journal of NeuroVirology.

[30]  Shivakundan Singh Tej,et al.  MicroRNAs and other small RNAs enriched in the Arabidopsis RNA-dependent RNA polymerase-2 mutant. , 2006, Genome research.

[31]  Zissimos Mourelatos,et al.  Microarray-based, high-throughput gene expression profiling of microRNAs , 2004, Nature Methods.

[32]  V. Chow,et al.  Transcriptomic and proteomic analyses of rhabdomyosarcoma cells reveal differential cellular gene expression in response to enterovirus 71 infection , 2005, Cellular microbiology.

[33]  Nectarios Koziris,et al.  Accurate microRNA target prediction correlates with protein repression levels , 2009, BMC Bioinformatics.

[34]  C. Croce,et al.  Human Cytomegalovirus Infection Alters the Expression of Cellular MicroRNA Species That Affect Its Replication , 2008, Journal of Virology.

[35]  Cheng-qiang He,et al.  Appearance of mosaic enterovirus 71 in the 2008 outbreak of China. , 2009, Virus research.

[36]  V. Ambros,et al.  Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation , 2004, Genome Biology.