Viruses, microRNAs, and host interactions.

One of the most significant recent advances in biomedical research has been the discovery of the approximately 22-nt-long class of noncoding RNAs designated microRNAs (miRNAs). These regulatory RNAs provide a unique level of posttranscriptional gene regulation that modulates a range of fundamental cellular processes. Several viruses, especially herpesviruses, also encode miRNAs, and over 200 viral miRNAs have now been identified. Current evidence indicates that viruses use these miRNAs to manipulate both cellular and viral gene expression. Furthermore, viral infection can exert a profound impact on the cellular miRNA expression profile, and several RNA viruses have been reported to interact directly with cellular miRNAs and/or to use these miRNAs to augment their replication potential. Here we discuss our current knowledge of viral miRNAs and virally influenced cellular miRNAs and their relationship to viral infection.

[1]  L. V. van Dyk,et al.  Mature and functional viral miRNAs transcribed from novel RNA polymerase III promoters. , 2010, RNA.

[2]  Alberto Riva,et al.  Kaposi's Sarcoma-Associated Herpesvirus Encodes an Ortholog of miR-155 , 2007, Journal of Virology.

[3]  Edward Yang,et al.  Human cytomegalovirus expresses novel microRNAs during productive viral infection , 2005, Cellular microbiology.

[4]  S. Pfeffer,et al.  Mouse Cytomegalovirus MicroRNAs Dominate the Cellular Small RNA Profile during Lytic Infection and Show Features of Posttranscriptional Regulation , 2007, Journal of Virology.

[5]  J. Burnside,et al.  Marek's Disease Virus Encodes MicroRNAs That Map to meq and the Latency-Associated Transcript , 2006, Journal of Virology.

[6]  N. Rajewsky,et al.  Widespread changes in protein synthesis induced by microRNAs , 2008, Nature.

[7]  Jay Nelson,et al.  Identification and Characterization of Human Cytomegalovirus-Encoded MicroRNAs , 2005, Journal of Virology.

[8]  J. Pipas,et al.  Complete Nucleotide Sequence of Polyomavirus SA12 , 2005, Journal of Virology.

[9]  D. Ganem,et al.  Tandem array–based expression screens identify host mRNA targets of virus-encoded microRNAs , 2009, Nature Genetics.

[10]  J. Nelson,et al.  Identification and function of human cytomegalovirus microRNAs. , 2008, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[11]  Paul Kellam,et al.  KSHV-encoded miRNAs target MAF to induce endothelial cell reprogramming. , 2010, Genes & development.

[12]  O. Aparicio,et al.  Adenovirus Virus-Associated RNA Is Processed to Functional Interfering RNAs Involved in Virus Production , 2006, Journal of Virology.

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

[14]  Noam Stern-Ginossar,et al.  Analysis of Human Cytomegalovirus-Encoded MicroRNA Activity during Infection , 2009, Journal of Virology.

[15]  B. Cullen,et al.  Cloning and analysis of microRNAs encoded by the primate gamma-herpesvirus rhesus monkey rhadinovirus. , 2007, Virology.

[16]  C. Beckham,et al.  P bodies, stress granules, and viral life cycles. , 2008, Cell host & microbe.

[17]  B. Cullen,et al.  Analysis of Human Alphaherpesvirus MicroRNA Expression in Latently Infected Human Trigeminal Ganglia , 2009, Journal of Virology.

[18]  T. Tuschl,et al.  Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. , 2004, Molecular cell.

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

[20]  Louis Flamand,et al.  Identification of functional microRNAs released through asymmetrical processing of HIV-1 TAR element† , 2008, Nucleic acids research.

[21]  N. Rajewsky,et al.  Regulation of the Germinal Center Response by MicroRNA-155 , 2007, Science.

[22]  J. Cohen,et al.  An acutely and latently expressed herpes simplex virus 2 viral microRNA inhibits expression of ICP34.5, a viral neurovirulence factor , 2008, Proceedings of the National Academy of Sciences.

[23]  E. Izaurralde,et al.  Getting to the Root of miRNA-Mediated Gene Silencing , 2008, Cell.

[24]  B. Cullen,et al.  Efficient Processing of Primary microRNA Hairpins by Drosha Requires Flanking Nonstructured RNA Sequences* , 2005, Journal of Biological Chemistry.

[25]  Wayne Tam,et al.  Reticuloendotheliosis Virus Strain T Induces miR-155, Which Targets JARID2 and Promotes Cell Survival , 2009, Journal of Virology.

[26]  E. Lai,et al.  The long and short of inverted repeat genes in animals: MicroRNAs, mirtrons and hairpin RNAs , 2008, Cell cycle.

[27]  J. Casey,et al.  RNA Editing of the Human Herpesvirus 8 Kaposin Transcript Eliminates Its Transforming Activity and Is Induced during Lytic Replication , 2007, Journal of Virology.

[28]  Phillip D. Zamore,et al.  Sorting of Drosophila Small Silencing RNAs , 2007, Cell.

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

[30]  M. Samols,et al.  Cloning and Identification of a MicroRNA Cluster within the Latency-Associated Region of Kaposi's Sarcoma-Associated Herpesvirus , 2005, Journal of Virology.

[31]  L. Xing,et al.  Epstein-Barr Virus BHRF1 Micro- and Stable RNAs during Latency III and after Induction of Replication , 2007, Journal of Virology.

[32]  Guanglin Li,et al.  Prediction and Identification of Herpes Simplex Virus 1-Encoded MicroRNAs , 2006, Journal of Virology.

[33]  Robert Blelloch,et al.  Mouse ES cells express endogenous shRNAs, siRNAs, and other Microprocessor-independent, Dicer-dependent small RNAs. , 2008, Genes & development.

[34]  Stefano Volinia,et al.  Interferon modulation of cellular microRNAs as an antiviral mechanism , 2007, Nature.

[35]  Klaus Rajewsky,et al.  MicroRNA Control in the Immune System: Basic Principles , 2009, Cell.

[36]  B. Segerman,et al.  Adenovirus Virus-Associated RNAII-Derived Small RNAs Are Efficiently Incorporated into the RNA-Induced Silencing Complex and Associate with Polyribosomes , 2007, Journal of Virology.

[37]  Bryan R. Cullen,et al.  Analysis of the Interaction of Primate Retroviruses with the Human RNA Interference Machinery , 2007, Journal of Virology.

[38]  Alberto Riva,et al.  Identification of Cellular Genes Targeted by KSHV-Encoded MicroRNAs , 2007, PLoS pathogens.

[39]  J. M. Thomson,et al.  Argonaute2 Is the Catalytic Engine of Mammalian RNAi , 2004, Science.

[40]  Alexandra Schäfer,et al.  Epstein–Barr Virus MicroRNAs Are Evolutionarily Conserved and Differentially Expressed , 2006, PLoS pathogens.

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

[42]  A. Fire,et al.  Patterns of known and novel small RNAs in human cervical cancer. , 2007, Cancer research.

[43]  Bryan R. Cullen,et al.  In-Depth Analysis of Kaposi's Sarcoma-Associated Herpesvirus MicroRNA Expression Provides Insights into the Mammalian MicroRNA-Processing Machinery , 2009, Journal of Virology.

[44]  S. Asgari,et al.  Functional Analysis of a Cellular MicroRNA in Insect Host-Ascovirus Interaction , 2009, Journal of Virology.

[45]  Olivier Voinnet,et al.  Antiviral Immunity Directed by Small RNAs , 2007, Cell.

[46]  Adam Drake,et al.  Virus-specific host miRNAs: antiviral defenses or promoters of persistent infection? , 2009, Trends in immunology.

[47]  I. Bozzoni,et al.  Epstein–Barr virus encoded LMP1 downregulates TCL1 oncogene through miR-29b , 2010, Oncogene.

[48]  R. Siliciano,et al.  Experimental approaches to the study of HIV-1 latency , 2007, Nature Reviews Microbiology.

[49]  K. Roemer,et al.  Epstein–Barr virus-encoded microRNA miR-BART2 down-regulates the viral DNA polymerase BALF5 , 2007, Nucleic acids research.

[50]  B. Cullen,et al.  A mammalian herpesvirus uses noncanonical expression and processing mechanisms to generate viral MicroRNAs. , 2010, Molecular cell.

[51]  Jirí Vanícek,et al.  Suppression of immediate-early viral gene expression by herpesvirus-coded microRNAs: Implications for latency , 2008, Proceedings of the National Academy of Sciences.

[52]  K. Taira,et al.  Sequence‐specific interference by small RNAs derived from adenovirus VAI RNA , 2006, FEBS letters.

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

[54]  Hanah Margalit,et al.  Host Immune System Gene Targeting by a Viral miRNA , 2007, Science.

[55]  G. Meister,et al.  Identification of Novel Epstein-Barr Virus MicroRNA Genes from Nasopharyngeal Carcinomas , 2009, Journal of Virology.

[56]  D. Kwong,et al.  An Epstein-Barr virus–encoded microRNA targets PUMA to promote host cell survival , 2008, The Journal of experimental medicine.

[57]  J. Burnside,et al.  MicroRNAs of Gallid and Meleagrid herpesviruses show generally conserved genomic locations and are virus-specific. , 2009, Virology.

[58]  M. Watson,et al.  MicroRNA Profile of Marek's Disease Virus-Transformed T-Cell Line MSB-1: Predominance of Virus-Encoded MicroRNAs , 2008, Journal of Virology.

[59]  D. Bartel,et al.  The impact of microRNAs on protein output , 2008, Nature.

[60]  C. Sander,et al.  Identification of microRNAs of the herpesvirus family , 2005, Nature Methods.

[61]  Adam Grundhoff,et al.  A combined computational and microarray-based approach identifies novel microRNAs encoded by human gamma-herpesviruses. , 2006, RNA.

[62]  Alicia Rodríguez-Huete,et al.  Evaluation of the Lytic Origins of Replication of Kaposi's Sarcoma-Associated Virus/Human Herpesvirus 8 in the Context of the Viral Genome , 2006, Journal of Virology.

[63]  Ryan Cook,et al.  Hypersusceptibility to vesicular stomatitis virus infection in Dicer1-deficient mice is due to impaired miR24 and miR93 expression. , 2007, Immunity.

[64]  G. Seo,et al.  Merkel cell polyomavirus encodes a microRNA with the ability to autoregulate viral gene expression. , 2009, Virology.

[65]  N. Rajewsky,et al.  A human snoRNA with microRNA-like functions. , 2008, Molecular cell.

[66]  F. Monzon,et al.  Human papillomavirus type 16 reduces the expression of microRNA-218 in cervical carcinoma cells , 2008, Oncogene.

[67]  J. Rader,et al.  Oncogenic HPV infection interrupts the expression of tumor-suppressive miR-34a through viral oncoprotein E6. , 2009, RNA.

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

[69]  R. Shiekhattar,et al.  TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing , 2005, Nature.

[70]  Bryan R. Cullen,et al.  Viral and cellular messenger RNA targets of viral microRNAs , 2009, Nature.

[71]  Hong Cao,et al.  Cellular microRNA and P bodies modulate host-HIV-1 interactions. , 2009, Molecular cell.

[72]  W. Filipowicz,et al.  Relief of microRNA-Mediated Translational Repression in Human Cells Subjected to Stress , 2006, Cell.

[73]  Blossom Damania,et al.  Kaposi's sarcoma-associated herpesvirus expresses an array of viral microRNAs in latently infected cells. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[74]  Eugene Berezikov,et al.  Mammalian mirtron genes. , 2007, Molecular cell.

[75]  Kwok Wai Lo,et al.  Modulation of LMP1 protein expression by EBV-encoded microRNAs , 2007, Proceedings of the National Academy of Sciences.

[76]  D. Spector,et al.  A Human Cytomegalovirus-Encoded microRNA Regulates Expression of Multiple Viral Genes Involved in Replication , 2007, PLoS pathogens.

[77]  James M. Pipas,et al.  SV40-encoded microRNAs regulate viral gene expression and reduce susceptibility to cytotoxic T cells , 2005, Nature.

[78]  B. Cullen,et al.  Adenovirus VA1 Noncoding RNA Can Inhibit Small Interfering RNA and MicroRNA Biogenesis , 2004, Journal of Virology.

[79]  B. Cullen,et al.  Identification of Viral MicroRNAs Expressed in Human Sacral Ganglia Latently Infected with Herpes Simplex Virus 2 , 2009, Journal of Virology.

[80]  B. Cullen,et al.  Expression and function of microRNAs encoded by Kaposi's sarcoma-associated herpesvirus. , 2006, Cold Spring Harbor symposia on quantitative biology.

[81]  R. Taft,et al.  An Insect Virus-Encoded MicroRNA Regulates Viral Replication , 2008, Journal of Virology.

[82]  S. Kauppinen,et al.  Therapeutic Silencing of MicroRNA-122 in Primates with Chronic Hepatitis C Virus Infection , 2010, Science.

[83]  A. Moses,et al.  Kaposi sarcoma-associated herpesvirus (KSHV) induces heme oxygenase-1 expression and activity in KSHV-infected endothelial cells. , 2004, Blood.

[84]  Zhen Lin,et al.  Epstein-Barr Virus Latent Membrane Protein 1 Induces Cellular MicroRNA miR-146a, a Modulator of Lymphocyte Signaling Pathways , 2007, Journal of Virology.

[85]  Stijn van Dongen,et al.  miRBase: microRNA sequences, targets and gene nomenclature , 2005, Nucleic Acids Res..

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

[87]  R. Berro,et al.  HIV-1 TAR element is processed by Dicer to yield a viral micro-RNA involved in chromatin remodeling of the viral LTR , 2007, BMC Molecular Biology.

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

[89]  S. Pfeffer,et al.  Post-transcriptional regulation of miR-27 in murine cytomegalovirus infection. , 2010, RNA.

[90]  Noam Stern-Ginossar,et al.  Diverse herpesvirus microRNAs target the stress-induced immune ligand MICB to escape recognition by natural killer cells. , 2009, Cell host & microbe.

[91]  Martin Reczko,et al.  Discrete Clusters of Virus-Encoded MicroRNAs Are Associated with Complementary Strands of the Genome and the 7.2-Kilobase Stable Intron in Murine Cytomegalovirus , 2007, Journal of Virology.

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

[93]  Anton J. Enright,et al.  Requirement of bic/microRNA-155 for Normal Immune Function , 2007, Science.

[94]  B. Cullen,et al.  Human Papillomavirus Genotype 31 Does Not Express Detectable MicroRNA Levels during Latent or Productive Virus Replication , 2006, Journal of Virology.

[95]  Catherine L Jopling,et al.  Position-dependent function for a tandem microRNA miR-122-binding site located in the hepatitis C virus RNA genome. , 2008, Cell host & microbe.

[96]  A. Grundhoff,et al.  A Global Analysis of Evolutionary Conservation among Known and Predicted Gammaherpesvirus MicroRNAs , 2009, Journal of Virology.

[97]  D. Bartel,et al.  Intronic microRNA precursors that bypass Drosha processing , 2007, Nature.

[98]  P. Krause,et al.  Novel Less-Abundant Viral MicroRNAs Encoded by Herpes Simplex Virus 2 Latency-Associated Transcript and Their Roles in Regulating ICP34.5 and ICP0 mRNAs , 2008, Journal of Virology.

[99]  B. O'Hara,et al.  Evolutionarily Conserved Function of a Viral MicroRNA , 2008, Journal of Virology.

[100]  D. Ganem,et al.  Murine Polyomavirus encodes a microRNA that cleaves early RNA transcripts but is not essential for experimental infection. , 2009, Virology.

[101]  Andrea J. O'Hara,et al.  EBV microRNAs in primary lymphomas and targeting of CXCL-11 by ebv-mir-BHRF1-3. , 2008, Cancer research.

[102]  D. Ganem,et al.  Regulation of KSHV lytic switch protein expression by a virus-encoded microRNA: an evolutionary adaptation that fine-tunes lytic reactivation. , 2009, Cell host & microbe.

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

[104]  M. Lacey,et al.  MicroRNA-155 Is an Epstein-Barr Virus-Induced Gene That Modulates Epstein-Barr Virus-Regulated Gene Expression Pathways , 2008, Journal of Virology.

[105]  M. Adams,et al.  Unconventional processing of the 3' termini of the Epstein-Barr virus DNA polymerase mRNA. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[106]  A. Saïb,et al.  A Cellular MicroRNA Mediates Antiviral Defense in Human Cells , 2005, Science.

[107]  M. Ronaghi,et al.  Six RNA Viruses and Forty-One Hosts: Viral Small RNAs and Modulation of Small RNA Repertoires in Vertebrate and Invertebrate Systems , 2010, PLoS pathogens.

[108]  Yongjun Yu,et al.  The TORrid affairs of viruses: effects of mammalian DNA viruses on the PI3K–Akt–mTOR signalling pathway , 2008, Nature Reviews Microbiology.

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

[110]  M. Zavolan,et al.  Marek's Disease Virus Type 2 (MDV-2)-Encoded MicroRNAs Show No Sequence Conservation with Those Encoded by MDV-1 , 2007, Journal of Virology.

[111]  Y. Lévy,et al.  Suppression of HIV-1 replication by microRNA effectors , 2009, Retrovirology.

[112]  Ben Berkhout,et al.  Suppression of RNA Interference by Adenovirus Virus-Associated RNA , 2005, Journal of Virology.

[113]  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.

[114]  J. Pipas,et al.  SV 40-encoded microRNAs regulate viral gene expression and reduce susceptibility to cytotoxic T cells , 2005 .