MicroRNA and Pathogenesis of Enterovirus Infection

There are no currently available specific antiviral therapies for non-polio Enterovirus infections. Although several vaccines have entered clinical trials, the efficacy requires further evaluation, particularly for cross-strain protective activity. Curing patients with viral infections is a public health problem due to antigen alterations and drug resistance caused by the high genomic mutation rate. To conquer these limits in the development of anti-Enterovirus treatments, a comprehensive understanding of the interactions between Enterovirus and host cells is urgently needed. MicroRNA (miRNA) constitutes the biggest family of gene regulators in mammalian cells and regulates almost a half of all human genes. The roles of miRNAs in Enterovirus pathogenesis have recently begun to be noted. In this review, we shed light on recent advances in the understanding of Enterovirus infection-modulated miRNAs. The impacts of altered host miRNAs on cellular processes, including immune escape, apoptosis, signal transduction, shutdown of host protein synthesis and viral replication, are discussed. Finally, miRNA-based medication provides a promising strategy for the development of antiviral therapy.

[1]  I. Yaylim,et al.  Is miR‐34a a Well‐equipped Swordsman to Conquer Temple of Molecular Oncology? , 2016, Chemical biology & drug design.

[2]  Xuejun Ma,et al.  Etiology of Multiple Non-EV71 and Non-CVA16 Enteroviruses Associated with Hand, Foot and Mouth Disease in Jinan, China, 2009—June 2013 , 2015, PloS one.

[3]  N. Grassly,et al.  The epidemiology of non-polio enteroviruses: recent advances and outstanding questions , 2015, Current opinion in infectious diseases.

[4]  Zhenglun Liang,et al.  Coxsackievirus A6: a new emerging pathogen causing hand, foot and mouth disease outbreaks worldwide , 2015, Expert review of anti-infective therapy.

[5]  J. Metzger,et al.  Severe dystrophic cardiomyopathy caused by the enteroviral protease 2A–mediated C-terminal dystrophin cleavage fragment , 2015, Science Translational Medicine.

[6]  S. Hammond An overview of microRNAs. , 2015, Advanced drug delivery reviews.

[7]  Sung-Liang Yu,et al.  miR‐146a and miR‐370 coordinate enterovirus 71‐induced cell apoptosis through targeting SOS1 and GADD45β , 2015, Cellular microbiology.

[8]  R. Gregory,et al.  MicroRNA biogenesis pathways in cancer , 2015, Nature Reviews Cancer.

[9]  P. Simmonds,et al.  Genetic characterization of human coxsackievirus A6 variants associated with atypical hand, foot and mouth disease: a potential role of recombination in emergence and pathogenicity , 2015, The Journal of general virology.

[10]  Yongyi Huang,et al.  Enterovirus 71 induces apoptosis of SH-SY5Y human neuroblastoma cells through stimulation of endogenous microRNA let-7b expression , 2015, Molecular medicine reports.

[11]  Haiyan Wei,et al.  Epidemiological and Etiological Characteristics of Hand, Foot, and Mouth Disease in Henan, China, 2008–2013 , 2015, Scientific Reports.

[12]  S. Tsui,et al.  miR‐466 is putative negative regulator of Coxsackie virus and Adenovirus Receptor , 2015, FEBS letters.

[13]  Yongjuan Liu,et al.  miR-27a suppresses EV71 replication by directly targeting EGFR , 2014, Virus Genes.

[14]  Y. Jeong,et al.  Clinical and enterovirus findings associated with acute flaccid paralysis in the republic of Korea during the recent decade , 2014, Journal of medical virology.

[15]  L. Lin,et al.  MiR-155 and miR-148a reduce cardiac injury by inhibiting NF-κB pathway during acute viral myocarditis. , 2014, European review for medical and pharmacological sciences.

[16]  C. Shin,et al.  MicroRNA-directed cleavage of targets: mechanism and experimental approaches , 2014, BMB reports.

[17]  Yanhong Zhang,et al.  Downregulation of MicroRNA miR-526a by Enterovirus Inhibits RIG-I-Dependent Innate Immune Response , 2014, Journal of Virology.

[18]  L. Tao,et al.  MicroRNA‑21 regulation of the progression of viral myocarditis to dilated cardiomyopathy. , 2014, Molecular medicine reports.

[19]  Q. Jin,et al.  Enterovirus 71 3C Inhibits Cytokine Expression through Cleavage of the TAK1/TAB1/TAB2/TAB3 Complex , 2014, Journal of Virology.

[20]  P. Tien,et al.  [MiR373 and miR542-5p regulate the replication of enterovirus 71 in rhabdomyosarcoma cells]. , 2014, Sheng wu gong cheng xue bao = Chinese journal of biotechnology.

[21]  R. Booy,et al.  The Causes and Consequences of Childhood Encephalitis in Asia. , 2014, Infectious disorders drug targets.

[22]  Yongqiang Deng,et al.  Parallel mRNA and MicroRNA Profiling of HEV71-Infected Human Neuroblastoma Cells Reveal the Up-Regulation of miR-1246 in Association with DLG3 Repression , 2014, PloS one.

[23]  Paul J. Hanson,et al.  Coxsackievirus-Induced miR-21 Disrupts Cardiomyocyte Interactions via the Downregulation of Intercalated Disk Components , 2014, PLoS pathogens.

[24]  Jianwei Wang,et al.  Enterovirus 68 3C Protease Cleaves TRIF To Attenuate Antiviral Responses Mediated by Toll-Like Receptor 3 , 2014, Journal of Virology.

[25]  F. Baldanti,et al.  Human enterovirus and parechovirus infections in newborns with sepsis-like illness and neurological disorders. , 2014, Early human development.

[26]  Jiansheng Liu,et al.  An inactivated enterovirus 71 vaccine in healthy children. , 2014, The New England journal of medicine.

[27]  Wenbo Xu,et al.  Efficacy, safety, and immunogenicity of an enterovirus 71 vaccine in China. , 2014, The New England journal of medicine.

[28]  A. Rudensky,et al.  Inhibition of miR-146a prevents enterovirus-induced death by restoring the production of type I interferon , 2014, Nature Communications.

[29]  Jen-Ren Wang,et al.  Epidemiology and seroepidemiology of human enterovirus 71 among Thai populations , 2014, Journal of Biomedical Science.

[30]  P. Fisher,et al.  Enterovirus 2Apro Targets MDA5 and MAVS in Infected Cells , 2014, Journal of Virology.

[31]  Szu-Wei Huang,et al.  Molecular Epidemiology of Enterovirus 71 Infection in the Central Region of Taiwan from 2002 to 2012 , 2013, PloS one.

[32]  H. Pan,et al.  Patterns of polymorphism and divergence in the VP1 gene of enterovirus 71 circulating in the Asia-Pacific region between 1994 and 2013. , 2013, Journal of virological methods.

[33]  Sarah S. Wilson,et al.  Antiviral Mechanisms of Human Defensins , 2013, Journal of Molecular Biology.

[34]  Paul J. Hanson,et al.  MiR-126 promotes coxsackievirus replication by mediating cross-talk of ERK1/2 and Wnt/β-catenin signal pathways , 2013, Cellular and Molecular Life Sciences.

[35]  S. Kauppinen,et al.  Treatment of HCV infection by targeting microRNA. , 2013, The New England journal of medicine.

[36]  B. Wen,et al.  MicroRNA-23b Inhibits Enterovirus 71 Replication through Downregulation of EV71 VPl Protein , 2013, Intervirology.

[37]  S. Xiong,et al.  MiR-21 confers resistance against CVB3-induced myocarditis by inhibiting PDCD4-mediated apoptosis. , 2013, Clinical and investigative medicine. Medecine clinique et experimentale.

[38]  J. Ilonen,et al.  Human enterovirus 71 strains in the background population and in hospital patients in Finland. , 2013, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[39]  Hanzhong Wang,et al.  Human MicroRNA hsa-miR-296-5p Suppresses Enterovirus 71 Replication by Targeting the Viral Genome , 2013, Journal of Virology.

[40]  A. Keren,et al.  Acute viral myocarditis: current concepts in diagnosis and treatment. , 2013, The Israel Medical Association journal : IMAJ.

[41]  Tianying Wang,et al.  MiR-10a* up-regulates coxsackievirus B3 biosynthesis by targeting the 3D-coding sequence , 2013, Nucleic acids research.

[42]  Ying-hua Zhu,et al.  MicroRNA-548 down-regulates host antiviral response via direct targeting of IFN-λ1 , 2013, Protein & Cell.

[43]  Qinghua Zhang,et al.  MicroRNAs Regulate the Pathogenesis of CVB3-Induced Viral Myocarditis , 2012, Intervirology.

[44]  Hefen Sun,et al.  Isocorydine Targets the Drug-Resistant Cellular Side Population through PDCD4-Related Apoptosis in Hepatocellular Carcinoma , 2012, Molecular medicine.

[45]  Stephane Heymans,et al.  MicroRNA Profiling Identifies MicroRNA-155 as an Adverse Mediator of Cardiac Injury and Dysfunction During Acute Viral Myocarditis , 2012, Circulation research.

[46]  A. Xue,et al.  MicroRNA- 1 represses Cx43 expression in viral myocarditis , 2012, Molecular and Cellular Biochemistry.

[47]  Z. Zhong,et al.  MiR-342-5p suppresses coxsackievirus B3 biosynthesis by targeting the 2C-coding region. , 2012, Antiviral research.

[48]  H. Hsieh,et al.  Enterovirus 71 induces integrin β1/EGFR‐Rac1‐dependent oxidative stress in SK‐N‐SH cells: Role of HO‐1/CO in viral replication , 2011, Journal of cellular physiology.

[49]  E. Stanbridge,et al.  Partial protection against enterovirus 71 (EV71) infection in a mouse model immunized with recombinant newcastle disease virus capsids displaying the EV71 VP1 fragment , 2011, Journal of medical virology.

[50]  K. Chua,et al.  Hand foot and mouth disease due to enterovirus 71 in Malaysia , 2011, Virologica Sinica.

[51]  B. Böttiger,et al.  Clinical and virological features of enterovirus 71 infections in Denmark, 2005 to 2008 , 2011, Scandinavian journal of infectious diseases.

[52]  Ashley P E Roberts,et al.  miR-122 activates hepatitis C virus translation by a specialized mechanism requiring particular RNA components , 2011, Nucleic acids research.

[53]  E. Kurt-Jones,et al.  Pattern Recognition Receptors and the Innate Immune Response to Viral Infection , 2011, Viruses.

[54]  H. Hsieh,et al.  Enterovirus 71 modulates a COX‐2/PGE2/cAMP‐dependent viral replication in human neuroblastoma cells: Role of the c‐Src/EGFR/p42/p44 MAPK/CREB signaling pathway , 2011, Journal of cellular biochemistry.

[55]  Ker-Chau Li,et al.  Enterovirus-induced miR-141 contributes to shutoff of host protein translation by targeting the translation initiation factor eIF4E. , 2011, Cell host & microbe.

[56]  P. Sarnow,et al.  RNA virus harnesses microRNAs to seize host translation control. , 2011, Cell host & microbe.

[57]  S. Trasti,et al.  Sustained High Levels of Interleukin-6 Contribute to the Pathogenesis of Enterovirus 71 in a Neonate Mouse Model , 2011, Journal of Virology.

[58]  Tom Solomon,et al.  Virology, epidemiology, pathogenesis, and control of enterovirus 71. , 2010, The Lancet. Infectious diseases.

[59]  W. Ryu,et al.  Enterovirus 71 Infection with Central Nervous System Involvement, South Korea , 2010, Emerging infectious diseases.

[60]  Guanming Wu,et al.  A Viral microRNA Down-Regulates Multiple Cell Cycle Genes through mRNA 5′UTRs , 2010, PLoS pathogens.

[61]  H. Hsieh,et al.  Enterovirus 71 induces COX-2 expression via MAPKs, NF-kappaB, and AP-1 in SK-N-SH cells: Role of PGE(2) in viral replication. , 2010, Cellular signalling.

[62]  Shainn-Wei Wang,et al.  Enterovirus 71 Infection of Human Dendritic Cells , 2009, Experimental biology and medicine.

[63]  Kow-Tong Chen,et al.  Diseases Caused by Enterovirus 71 Infection , 2009, The Pediatric infectious disease journal.

[64]  C. Croce Causes and consequences of microRNA dysregulation in cancer , 2009, Nature Reviews Genetics.

[65]  Chunxiang Zhang,et al.  MicroRNA-21 protects against the H(2)O(2)-induced injury on cardiac myocytes via its target gene PDCD4. , 2009, Journal of molecular and cellular cardiology.

[66]  Brian D Athey,et al.  New class of microRNA targets containing simultaneous 5'-UTR and 3'-UTR interaction sites. , 2009, Genome research.

[67]  B. Cullen,et al.  The role of RNAi and microRNAs in animal virus replication and antiviral immunity. , 2009, Genes & development.

[68]  I. Rigoutsos New tricks for animal microRNAS: targeting of amino acid coding regions at conserved and nonconserved sites. , 2009, Cancer research.

[69]  V. Kim,et al.  Regulation of microRNA biogenesis , 2014, Nature Reviews Molecular Cell Biology.

[70]  R. Gregory,et al.  Many roads to maturity: microRNA biogenesis pathways and their regulation , 2009, Nature Cell Biology.

[71]  D. Bartel MicroRNAs: Target Recognition and Regulatory Functions , 2009, Cell.

[72]  B. Cullen,et al.  MicroRNAs expressed by herpes simplex virus 1 during latent infection regulate viral mRNAs , 2008, Nature.

[73]  U. A. Ørom,et al.  MicroRNA-10a binds the 5'UTR of ribosomal protein mRNAs and enhances their translation. , 2008, Molecular cell.

[74]  Reuven Agami,et al.  miR-148 targets human DNMT3b protein coding region. , 2008, RNA.

[75]  A. Krogh,et al.  Programmed Cell Death 4 (PDCD4) Is an Important Functional Target of the MicroRNA miR-21 in Breast Cancer Cells* , 2008, Journal of Biological Chemistry.

[76]  Bryan R. Cullen,et al.  A viral microRNA functions as an orthologue of cellular miR-155 , 2007, Nature.

[77]  P. Pantelidis,et al.  Genetic evolution of enterovirus 71: epidemiological and pathological implications , 2007, Reviews in medical virology.

[78]  Richard J Jackson,et al.  MicroRNAs repress translation of m7Gppp-capped target mRNAs in vitro by inhibiting initiation and promoting deadenylation. , 2007, Genes & development.

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

[80]  Pascal Barbry,et al.  Suppression of MicroRNA-Silencing Pathway by HIV-1 During Virus Replication , 2007, Science.

[81]  B. Davidson,et al.  RNA polymerase III transcribes human microRNAs , 2006, Nature Structural &Molecular Biology.

[82]  Theresa L. Chang,et al.  Defensins in innate antiviral immunity , 2006, Nature Reviews Immunology.

[83]  Ligang Wu,et al.  MicroRNAs direct rapid deadenylation of mRNA. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[84]  S. Hammond,et al.  MicroRNAs as oncogenes. , 2006, Current opinion in genetics & development.

[85]  Shizuo Akira,et al.  Innate immune recognition of viral infection , 2006, Nature Immunology.

[86]  H. Lei,et al.  Type I interferons protect mice against enterovirus 71 infection. , 2005, The Journal of general virology.

[87]  J. Whitton,et al.  Host and virus determinants of picornavirus pathogenesis and tropism , 2005, Nature Reviews Microbiology.

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

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

[90]  B. Cullen Transcription and processing of human microRNA precursors. , 2004, Molecular cell.

[91]  H. Lei,et al.  A Mouse-Adapted Enterovirus 71 Strain Causes Neurological Disease in Mice after Oral Infection , 2004, Journal of Virology.

[92]  P. Sarnow,et al.  Proteolytic Cleavage of the Catalytic Subunit of DNA-Dependent Protein Kinase during Poliovirus Infection , 2004, Journal of Virology.

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

[94]  R. Lloyd,et al.  Cleavage of Poly(A)-Binding Protein by Poliovirus 3C Protease Inhibits Host Cell Translation: a Novel Mechanism for Host Translation Shutoff , 2004, Molecular and Cellular Biology.

[95]  I. Mohr,et al.  Translation initiation and viral tricks. , 2003, Trends in biochemical sciences.

[96]  K. Jerome,et al.  APOPTOSIS PREVENTION AS A MECHANISM OF IMMUNE EVASION , 2003, International reviews of immunology.

[97]  V. Chow,et al.  Complete Sequence Analyses of Enterovirus 71 Strains from Fatal and Non‐Fatal Cases of the Hand, Foot and Mouth Disease Outbreak in Singapore (2000) , 2002, Microbiology and immunology.

[98]  R. Salomon,et al.  Critical Role for STAT4 Activation by Type 1 Interferons in the Interferon-γ Response to Viral Infection , 2002, Science.

[99]  S. Kung,et al.  Infection with enterovirus 71 or expression of its 2A protease induces apoptotic cell death. , 2002, The Journal of general virology.

[100]  A. Pasquinelli,et al.  Genes and Mechanisms Related to RNA Interference Regulate Expression of the Small Temporal RNAs that Control C. elegans Developmental Timing , 2001, Cell.

[101]  A. Pasquinelli,et al.  A Cellular Function for the RNA-Interference Enzyme Dicer in the Maturation of the let-7 Small Temporal RNA , 2001, Science.

[102]  F. Belardelli,et al.  Type i interferons potently enhance humoral immunity and can promote isotype switching by stimulating dendritic cells in vivo. , 2001, Immunity.

[103]  A. Caudy,et al.  Role for a bidentate ribonuclease in the initiation step of RNA interference , 2001 .

[104]  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.

[105]  N. Sonenberg,et al.  Picornavirus RNA translation: roles for cellular proteins. , 2000, Trends in microbiology.

[106]  S. Hammond,et al.  An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells , 2000, Nature.

[107]  N. Sonenberg,et al.  Poliovirus 2A Protease Induces Apoptotic Cell Death , 2000, Molecular and Cellular Biology.

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

[109]  J. Sprent,et al.  Stimulation of naive and memory T cells by cytokines , 1999, Immunological reviews.

[110]  Y. Okuno,et al.  Enterovirus 71 from fatal and nonfatal cases of hand, foot and mouth disease epidemics in Malaysia, Japan and Taiwan in 1997-1998. , 1999, Japanese journal of infectious diseases.

[111]  Yhu-Chering Huang,et al.  Fulminant neurogenic pulmonary oedema with hand, foot, and mouth disease , 1998, The Lancet.

[112]  T. Kurimura,et al.  Neutralizing antibody and interferon‐α in cerebrospinal fluids and sera of acute aseptic meningitis , 1985, Journal of medical virology.

[113]  S. Jun Epidemiological and etiological characteristics of hand,foot and mouth disease in Shanghai,2009-2011 , 2013 .

[114]  Paul J. Hanson,et al.  MicroRNA-203 enhances Coxsackievirus B3 replication through targeting zinc finger protein-148 , 2012, Cellular and Molecular Life Sciences.

[115]  C. Biron,et al.  Natural killer cells in antiviral defense: function and regulation by innate cytokines. , 1999, Annual review of immunology.