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PLOS ONE  2014 

Enterovirus71 (EV71) Utilise Host microRNAs to Mediate Host Immune System Enhancing Survival during Infection

DOI: 10.1371/journal.pone.0102997

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Hand, Foot and Mouth Disease (HFMD) is a self-limiting viral disease that mainly affects infants and children. In contrast with other HFMD causing enteroviruses, Enterovirus71 (EV71) has commonly been associated with severe clinical manifestation leading to death. Currently, due to a lack in understanding of EV71 pathogenesis, there is no antiviral therapeutics for the treatment of HFMD patients. Therefore the need to better understand the mechanism of EV71 pathogenesis is warranted. We have previously reported a human colorectal adenocarcinoma cell line (HT29) based model to study the pathogenesis of EV71. Using this system, we showed that knockdown of DGCR8, an essential cofactor for microRNAs biogenesis resulted in a reduction of EV71 replication. We also demonstrated that there are miRNAs changes during EV71 pathogenesis and EV71 utilise host miRNAs to attenuate antiviral pathways during infection. Together, data from this study provide critical information on the role of miRNAs during EV71 infection.


[1]  Lui YLE, Lin Z, Lee JJ, Chow VTK, Poh CL, et al. (2013) Beta-actin variant is necessary for Enterovirus 71 replication. Biochemical and Biophysical Research Communications 433: 607–610. doi: 10.1016/j.bbrc.2013.03.044
[2]  McMinn PC (2002) An overview of the evolution of enterovirus 71 and its clinical and public health significance. FEMS Microbiol Rev 26: 91–107. doi: 10.1111/j.1574-6976.2002.tb00601.x
[3]  McMinn PC (2012) Recent advances in the molecular epidemiology and control of human enterovirus 71 infection. Curr Opin Virol 2: 199–205. doi: 10.1016/j.coviro.2012.02.009
[4]  Ooi MH, Wong SC, Lewthwaite P, Cardosa MJ, Solomon T (2010) Clinical features, diagnosis, and management of enterovirus 71. Lancet Neurol 9: 1097–1105. doi: 10.1016/s1474-4422(10)70209-x
[5]  Patel KP, Bergelson JM (2009) Receptors identified for hand, foot and mouth virus. Nat Med 15: 728–729. doi: 10.1038/nm0709-728
[6]  Solomon T, Lewthwaite P, Perera D, Cardosa MJ, McMinn P, et al. (2010) Virology, epidemiology, pathogenesis, and control of enterovirus 71. Lancet Infect Dis 10: 778–790. doi: 10.1016/s1473-3099(10)70194-8
[7]  Wong SS, Yip CC, Lau SK, Yuen KY (2010) Human enterovirus 71 and hand, foot and mouth disease. Epidemiol Infect 138: 1071–1089. doi: 10.1017/s0950268809991555
[8]  Ho BC, Yu SL, Chen JJ, Chang SY, Yan BS, et al. (2011) Enterovirus-induced miR-141 contributes to shutoff of host protein translation by targeting the translation initiation factor eIF4E. Cell Host Microbe 9: 58–69. doi: 10.1016/j.chom.2010.12.001
[9]  Huang HI, Weng KF, Shih SR (2012) Viral and host factors that contribute to pathogenicity of enterovirus 71. Future Microbiol 7: 467–479. doi: 10.2217/fmb.12.22
[10]  Chu PY, Lin KH, Hwang KP, Chou LC, Wang CF, et al. (2001) Molecular epidemiology of enterovirus 71 in Taiwan. Arch Virol 146: 589–600. doi: 10.1007/s007050170164
[11]  Lee JJ, Seah JB, Chow VT, Poh CL, Tan EL (2011) Comparative proteome analyses of host protein expression in response to Enterovirus 71 and Coxsackievirus A16 infections. J Proteomics 74: 2018–2024. doi: 10.1016/j.jprot.2011.05.022
[12]  Lee MS, Chang LY (2010) Development of enterovirus 71 vaccines. Expert Rev Vaccines 9: 149–156. doi: 10.1586/erv.09.152
[13]  Lee MS, Tseng FC, Wang JR, Chi CY, Chong P, et al. (2012) Challenges to licensure of enterovirus 71 vaccines. PLoS Negl Trop Dis 6: e1737. doi: 10.1371/journal.pntd.0001737
[14]  Viswanathan K, Fruh K, DeFilippis V (2010) Viral hijacking of the host ubiquitin system to evade interferon responses. Curr Opin Microbiol 13: 517–523. doi: 10.1016/j.mib.2010.05.012
[15]  tenOever BR (2013) RNA viruses and the host microRNA machinery. Nat Rev Microbiol 11: 169–180. doi: 10.1038/nrmicro2971
[16]  Taylor KE, Mossman KL (2013) Recent advances in understanding viral evasion of type I interferon. Immunology 138: 190–197. doi: 10.1111/imm.12038
[17]  Randall RE, Goodbourn S (2008) Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures. J Gen Virol 89: 1–47. doi: 10.1099/vir.0.83391-0
[18]  Rajsbaum R, Garcia-Sastre A (2013) Viral evasion mechanisms of early antiviral responses involving regulation of ubiquitin pathways. Trends Microbiol 21: 421–429. doi: 10.1016/j.tim.2013.06.006
[19]  Munday DC, Surtees R, Emmott E, Dove BK, Digard P, et al. (2012) Using SILAC and quantitative proteomics to investigate the interactions between viral and host proteomes. Proteomics 12: 666–672. doi: 10.1002/pmic.201100488
[20]  Versteeg GA, Garcia-Sastre A (2010) Viral tricks to grid-lock the type I interferon system. Curr Opin Microbiol 13: 508–516. doi: 10.1016/j.mib.2010.05.009
[21]  Thompson MR, Kaminski JJ, Kurt-Jones EA, Fitzgerald KA (2011) Pattern recognition receptors and the innate immune response to viral infection. Viruses 3: 920–940. doi: 10.3390/v3060920
[22]  Oudshoorn D, Versteeg GA, Kikkert M (2012) Regulation of the innate immune system by ubiquitin and ubiquitin-like modifiers. Cytokine Growth Factor Rev 23: 273–282. doi: 10.1016/j.cytogfr.2012.08.003
[23]  de Weerd NA, Nguyen T (2012) The interferons and their receptors–distribution and regulation. Immunol Cell Biol 90: 483–491. doi: 10.1038/icb.2012.9
[24]  Brennan K, Bowie AG (2010) Activation of host pattern recognition receptors by viruses. Curr Opin Microbiol 13: 503–507. doi: 10.1016/j.mib.2010.05.007
[25]  Boss IW, Renne R (2011) Viral miRNAs and immune evasion. Biochim Biophys Acta 1809: 708–714. doi: 10.1016/j.bbagrm.2011.06.012
[26]  Kanarek N, Ben-Neriah Y (2012) Regulation of NF-kappaB by ubiquitination and degradation of the IkappaBs. Immunol Rev 246: 77–94. doi: 10.1111/j.1600-065x.2012.01098.x
[27]  Sullivan CS, Ganem D (2005) MicroRNAs and viral infection. Mol Cell 20: 3–7. doi: 10.1016/j.molcel.2005.09.012
[28]  Scaria V, Hariharan M, Maiti S, Pillai B, Brahmachari SK (2006) Host-virus interaction: a new role for microRNAs. Retrovirology 3: 68. doi: 10.1186/1742-4690-3-68
[29]  Ghosh Z, Mallick B, Chakrabarti J (2009) Cellular versus viral microRNAs in host-virus interaction. Nucleic Acids Res 37: 1035–1048. doi: 10.1093/nar/gkn1004
[30]  Lau NC, Lim LP, Weinstein EG, Bartel DP (2001) An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science 294: 858–862. doi: 10.1126/science.1065062
[31]  Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75: 843–854. doi: 10.1016/0092-8674(93)90529-y
[32]  Skalsky RL, Cullen BR (2010) Viruses, microRNAs, and host interactions. Annu Rev Microbiol 64: 123–141. doi: 10.1146/annurev.micro.112408.134243
[33]  Nathans R, Chu CY, Serquina AK, Lu CC, Cao H, et al. (2009) Cellular microRNA and P bodies modulate host-HIV-1 interactions. Mol Cell 34: 696–709. doi: 10.1016/j.molcel.2009.06.003
[34]  Mack GS (2007) MicroRNA gets down to business. Nat Biotechnol 25: 631–638. doi: 10.1038/nbt0607-631
[35]  Lui Y, Timms P, Hafner L, Tan T, Tan K, et al. (2013) Characterisation of enterovirus 71 replication kinetics in human colorectal cell line, HT29. SpringerPlus 2: 267. doi: 10.1186/2193-1801-2-267
[36]  Berkhout B, Jeang KT (2007) RISCy business: MicroRNAs, pathogenesis, and viruses. J Biol Chem 282: 26641–26645. doi: 10.1074/jbc.r700023200
[37]  Lecellier CH, Dunoyer P, Arar K, Lehmann-Che J, Eyquem S, et al. (2005) A cellular microRNA mediates antiviral defense in human cells. Science 308: 557–560. doi: 10.1126/science.1108784
[38]  Gottwein E, Cullen BR (2008) Viral and cellular microRNAs as determinants of viral pathogenesis and immunity. Cell Host Microbe 3: 375–387. doi: 10.1016/j.chom.2008.05.002
[39]  Sullivan CS (2008) New roles for large and small viral RNAs in evading host defences. Nat Rev Genet 9: 503–507. doi: 10.1038/nrg2349
[40]  Boss IW, Renne R (2010) Viral miRNAs: tools for immune evasion. Curr Opin Microbiol 13: 540–545. doi: 10.1016/j.mib.2010.05.017
[41]  Roberts AP, Jopling CL (2010) Targeting viral infection by microRNA inhibition. Genome Biol 11: 201. doi: 10.1186/gb-2010-11-1-201
[42]  Chable-Bessia C, Meziane O, Latreille D, Triboulet R, Zamborlini A, et al. (2009) Suppression of HIV-1 replication by microRNA effectors. Retrovirology 6: 26. doi: 10.1186/1742-4690-6-26
[43]  Triboulet R, Mari B, Lin Y, Chable-Bessia C, Bennasser Y, et al. (2007) Suppression of microRNA-silencing pathway by HIV-1 during virus replication. Science 315: 1579–1582. doi: 10.1126/science.1136319
[44]  Otsuka M, Jing Q, Georgel P, New L, Chen J, et al. (2007) Hypersusceptibility to vesicular stomatitis virus infection in Dicer1-deficient mice is due to impaired miR24 and miR93 expression. Immunity 27: 123–134. doi: 10.1016/j.immuni.2007.05.014
[45]  Buck AH, Perot J, Chisholm MA, Kumar DS, Tuddenham L, et al. (2010) Post-transcriptional regulation of miR-27 in murine cytomegalovirus infection. RNA 16: 307–315. doi: 10.1261/rna.1819210
[46]  Cameron JE, Yin Q, Fewell C, Lacey M, McBride J, et al. (2008) Epstein-Barr virus latent membrane protein 1 induces cellular MicroRNA miR-146a, a modulator of lymphocyte signaling pathways. J Virol 82: 1946–1958. doi: 10.1128/jvi.02136-07
[47]  Huang J, Wang F, Argyris E, Chen K, Liang Z, et al. (2007) Cellular microRNAs contribute to HIV-1 latency in resting primary CD4+ T lymphocytes. Nat Med 13: 1241–1247. doi: 10.1038/nm1639
[48]  Jopling CL, Schutz S, Sarnow P (2008) Position-dependent function for a tandem microRNA miR-122-binding site located in the hepatitis C virus RNA genome. Cell Host Microbe 4: 77–85. doi: 10.1016/j.chom.2008.05.013
[49]  Lanford RE, Hildebrandt-Eriksen ES, Petri A, Persson R, Lindow M, et al. (2010) Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science 327: 198–201. doi: 10.1126/science.1178178
[50]  Martinez I, Gardiner AS, Board KF, Monzon FA, Edwards RP, et al. (2008) Human papillomavirus type 16 reduces the expression of microRNA-218 in cervical carcinoma cells. Oncogene 27: 2575–2582. doi: 10.1038/sj.onc.1210919
[51]  Yoshikawa T, Takata A, Otsuka M, Kishikawa T, Kojima K, et al. (2012) Silencing of microRNA-122 enhances interferon-alpha signaling in the liver through regulating SOCS3 promoter methylation. Sci Rep 2: 637. doi: 10.1038/srep00637
[52]  Wiertz E, Hill A, Tortorella D, Ploegh H (1997) Cytomegaloviruses use multiple mechanisms to elude the host immune response. Immunol Lett 57: 213–216. doi: 10.1016/s0165-2478(97)00073-4
[53]  Jopling CL, Norman KL, Sarnow P (2006) Positive and negative modulation of viral and cellular mRNAs by liver-specific microRNA miR-122. Cold Spring Harb Symp Quant Biol 71: 369–376. doi: 10.1101/sqb.2006.71.022
[54]  Jopling CL, Yi M, Lancaster AM, Lemon SM, Sarnow P (2005) Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science 309: 1577–1581. doi: 10.1126/science.1113329
[55]  Randall G, Panis M, Cooper JD, Tellinghuisen TL, Sukhodolets KE, et al. (2007) Cellular cofactors affecting hepatitis C virus infection and replication. Proc Natl Acad Sci U S A 104: 12884–12889. doi: 10.1073/pnas.0704894104
[56]  Wen BP, Dai HJ, Yang YH, Zhuang Y, Sheng R (2013) MicroRNA-23b Inhibits Enterovirus 71 Replication through Downregulation of EV71 VPl Protein. Intervirology 56: 195–200. doi: 10.1159/000348504
[57]  Zheng Z, Ke X, Wang M, He S, Li Q, et al. (2013) Human microRNA hsa-miR-296-5p suppresses Enterovirus 71 replication by targeting the viral genome. J Virol.
[58]  Ho BC, Yu IS, Lu LF, Rudensky A, Chen HY, et al. (2014) Inhibition of miR-146a prevents enterovirus-induced death by restoring the production of type I interferon. Nat Commun 5: 3344. doi: 10.1038/ncomms4344
[59]  Li Y, Xie J, Xu X, Wang J, Ao F, et al. (2013) MicroRNA-548 down-regulates host antiviral response via direct targeting of IFN-lambda1. Protein Cell 4: 130–141. doi: 10.1007/s13238-012-2081-y
[60]  Lo AK, To KF, Lo KW, Lung RW, Hui JW, et al. (2007) Modulation of LMP1 protein expression by EBV-encoded microRNAs. Proc Natl Acad Sci U S A 104: 16164–16169. doi: 10.1073/pnas.0702896104
[61]  Xiao C, Rajewsky K (2009) MicroRNA control in the immune system: basic principles. Cell 136: 26–36.
[62]  Liu ML, Lee YP, Wang YF, Lei HY, Liu CC, et al. (2005) Type I interferons protect mice against enterovirus 71 infection. J Gen Virol 86: 3263–3269. doi: 10.1099/vir.0.81195-0
[63]  Lui YLE, Tan TL, Timms P, Hafner LM, Tan KH, et al. (2014) Elucidating the host–pathogen interaction between human colorectal cells and invading Enterovirus 71 using transcriptomics profiling. FEBS Open Bio 4: 426–431. doi: 10.1016/j.fob.2014.04.005
[64]  Reed LJ, Muench H (1938) A simple method of estimating fifty percent endpoints. The American Journal of Hygiene 27: 493–497.
[65]  Tan EL, Chow VT, Quak SH, Yeo WC, Poh CL (2008) Development of multiplex real-time hybridization probe reverse transcriptase polymerase chain reaction for specific detection and differentiation of Enterovirus 71 and Coxsackievirus A16. Diagn Microbiol Infect Dis 61: 294–301. doi: 10.1016/j.diagmicrobio.2008.02.009
[66]  Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25: 402–408. doi: 10.1006/meth.2001.1262


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