title: RNA viruses and microRNAs: challenging discoveries for the 21st century.
abstract: RNA viruses represent the predominant cause of many clinically relevant viral diseases in humans. Among several evolutionary advantages acquired by RNA viruses, the ability to usurp host cellular machinery and evade antiviral immune responses is imperative. During the past decade, RNA interference mechanisms, especially microRNA (miRNA)-mediated regulation of cellular protein expression, have revolutionized our understanding of host-viral interactions. Although it is well established that several DNA viruses express miRNAs that play crucial roles in their pathogenesis, expression of miRNAs by RNA viruses remains controversial. However, modulation of the miRNA machinery by RNA viruses may confer multiple benefits for enhanced viral replication and survival in host cells. In this review, we discuss the current literature on RNA viruses that may encode miRNAs and the varied advantages of engineering RNA viruses to express miRNAs as potential vectors for gene therapy. In addition, we review how different families of RNA viruses can alter miRNA machinery for productive replication, evasion of antiviral immune responses, and prolonged survival. We underscore the need to further explore the complex interactions of RNA viruses with host miRNAs to augment our understanding of host-virus interplay.
authors.affiliation: Microbiology and Immunology Graduate Program, Drexel University College of Medicine, Philadelphia, Pennsylvania;
authors.forename: Gokul
authors.initials: G
authors.lastname: Swaminathan
authors.forename: Julio
authors.initials: J
authors.lastname: Martin-Garcia
authors.forename: Sonia
authors.initials: S
authors.lastname: Navas-Martin
mesh_terms: D000818:Animals; D015316:Genetic Therapy; D005822:Genetic Vectors; D054884:Host-Pathogen Interactions; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D012327:RNA Virus Infections / Q000235:genetics / Q000628:therapy; D012328:RNA Viruses / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D012367:RNA, Viral
keywords: RNA virus; microRNA; pathogenesis
references.citation: Blood. 2009 Jan 15;113(3):671-4
references.pmid: 19015395
references.citation: PLoS One. 2013;8(1):e54506
references.pmid: 23349911
references.citation: Science. 2007 Mar 16;315(5818):1579-82
references.pmid: 17322031
references.citation: J Biol Chem. 2012 Sep 7;287(37):31027-40
references.pmid: 22822053
references.citation: mBio. 2010 Sep 14;1(4):
references.pmid: 20842206
references.citation: Virology. 2005 Mar 15;333(2):215-25
references.pmid: 15721356
references.citation: RNA Biol. 2012 Feb;9(2):137-42
references.pmid: 22258222
references.citation: RNA. 2013 Jun;19(6):737-9
references.pmid: 23554231
references.citation: J Mol Biol. 2013 Oct 9;425(19):3582-600
references.pmid: 23500488
references.citation: Retrovirology. 2008 Dec 23;5:117
references.pmid: 19102781
references.citation: J Gene Med. 2006 Aug;8(8):933-50
references.pmid: 16779870
references.citation: J Virol. 2012 May;86(9):5278-87
references.pmid: 22345437
references.citation: J Virol. 2012 Jun;86(11):6109-22
references.pmid: 22438559
references.citation: Science. 2001 Oct 26;294(5543):862-4
references.pmid: 11679672
references.citation: Nucleic Acids Res. 2010 Dec;38(22):8328-37
references.pmid: 20705652
references.citation: Virology. 2013 Mar 30;438(1):1-4
references.pmid: 23357732
references.citation: PLoS Pathog. 2012 Sep;8(9):e1002937
references.pmid: 23028330
references.citation: Pharmacol Res. 2013 Sep;75:48-59
references.pmid: 23541631
references.citation: Mol Cell Biochem. 2009 Mar;323(1-2):143-8
references.pmid: 19082544
references.citation: J Virol. 2010 Sep;84(17):8849-60
references.pmid: 20554777
references.citation: Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):11869-74
references.pmid: 23818585
references.citation: BioDrugs. 2012 Jun 1;26(3):131-41
references.pmid: 22494429
references.citation: Curr Anesthesiol Rep. 2013 Mar 1;1(1):63-70
references.pmid: 23524956
references.citation: BMC Infect Dis. 2013 Jun 03;13:257
references.pmid: 23731466
references.citation: Nucleic Acids Res. 2012 Mar;40(5):2210-23
references.pmid: 22080551
references.citation: Nucleic Acids Res. 2011 Sep 1;39(17):7716-29
references.pmid: 21653556
references.citation: Hypertension. 2013 Sep;62(3):592-8
references.pmid: 23817492
references.citation: Cell Microbiol. 2013 Sep;15(9):1496-507
references.pmid: 23795564
references.citation: Arthritis Rheum. 2009 Apr;60(4):1065-75
references.pmid: 19333922
references.citation: Nat Methods. 2005 Apr;2(4):269-76
references.pmid: 15782219
references.citation: Retrovirology. 2004 Dec 15;1:43
references.pmid: 15601472
references.citation: Curr Biol. 2004 Dec 14;14(23):2162-7
references.pmid: 15589161
references.citation: PLoS Pathog. 2009 Jul;5(7):e1000502
references.pmid: 19578437
references.citation: PLoS Pathog. 2009 May;5(5):e1000440
references.pmid: 19461878
references.citation: Mol Cell Biol. 2010 Mar;30(6):1486-94
references.pmid: 20065043
references.citation: Gastroenterol Clin Biol. 2010 Sep;34(8-9):431-5
references.pmid: 20537478
references.citation: PLoS One. 2013;8(3):e58586
references.pmid: 23520522
references.citation: Immunol Rev. 2013 May;253(1):53-64
references.pmid: 23550638
references.citation: J Genet. 2010 Dec;89(4):527-37
references.pmid: 21273705
references.citation: Nature. 2010 Aug 12;466(7308):835-40
references.pmid: 20703300
references.citation: Chem Biol Drug Des. 2013 Jan;81(1):79-84
references.pmid: 22834637
references.citation: Front Neurosci. 2013 Jan 17;6:196
references.pmid: 23335878
references.citation: J Cell Mol Med. 2012 Oct;16(10):2539-46
references.pmid: 22452878
references.citation: J Virol. 2012 May;86(10):5647-59
references.pmid: 22419812
references.citation: Retrovirology. 2004 Dec 15;1:44
references.pmid: 15601474
references.citation: Virology. 2009 Apr 25;387(1):157-67
references.pmid: 19272626
references.citation: Nature. 2005 Dec 1;438(7068):685-9
references.pmid: 16258535
references.citation: Proc Natl Acad Sci U S A. 2013 Jun 18;110(25):10276-81
references.pmid: 23733960
references.citation: Nature. 1987 Dec 3-9;330(6147):489-93
references.pmid: 2825027
references.citation: J Immunol. 2012 Aug 1;189(3):1448-58
references.pmid: 22745379
references.citation: J Virol. 2013 Aug;87(16):8870-83
references.pmid: 23741001
references.citation: J Immunol. 2010 Nov 15;185(10):6226-33
references.pmid: 20937844
references.citation: PLoS Negl Trop Dis. 2012;6(7):e1735
references.pmid: 22848770
references.citation: J Cell Biol. 2012 Oct 29;199(3):407-12
references.pmid: 23109665
references.citation: J Virol. 2010 Feb;84(3):1550-62
references.pmid: 19906911
references.citation: Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4991-6
references.pmid: 21383155
references.citation: Viruses. 2012 Sep 25;4(10):1844-64
references.pmid: 23202444
references.citation: Retrovirology. 2005 Dec 28;2:81
references.pmid: 16381609
references.citation: Curr Opin Virol. 2011 Sep;1(3):211-5
references.pmid: 21927637
references.citation: Future Virol. 2010 Sep 1;5(5):539-543
references.pmid: 21318128
references.citation: J Gen Virol. 2005 Mar;86(Pt 3):751-755
references.pmid: 15722536
references.citation: Clin Dev Immunol. 2013;2013:186872
references.pmid: 23762086
references.citation: Proc Natl Acad Sci U S A. 2013 Feb 5;110(6):2306-11
references.pmid: 23345446
references.citation: PLoS One. 2011;6(12):e28548
references.pmid: 22163034
references.citation: PLoS One. 2013 Jun 21;8(6):e66577
references.pmid: 23805240
references.citation: Nephrol Dial Transplant. 2014 Apr;29(4):755-63
references.pmid: 23787546
references.citation: Curr Top Med Chem. 2013;13(13):1605-18
references.pmid: 23745812
references.citation: Nat Med. 2007 Oct;13(10):1241-7
references.pmid: 17906637
references.citation: Science. 2005 Sep 2;309(5740):1577-81
references.pmid: 16141076
references.citation: New Microbiol. 2013 Jan;36(1):1-22
references.pmid: 23435812
references.citation: Chaos. 2010 Jun;20(2):026106
references.pmid: 20590335
references.citation: Genes Dev. 2009 May 15;23(10):1151-64
references.pmid: 19451215
references.citation: PLoS Pathog. 2013;9(4):e1003248
references.pmid: 23633945
references.citation: Hepatology. 2010 May;51(5):1494-504
references.pmid: 20127796
references.citation: PLoS One. 2013 May 01;8(5):e62965
references.pmid: 23650540
references.citation: J Virol. 2006 Apr;80(7):3559-66
references.pmid: 16537624
references.citation: Glia. 2013 Jan;61(1):91-103
references.pmid: 22653784
references.citation: Expert Opin Drug Deliv. 2013 Sep;10(9):1259-73
references.pmid: 23826971
references.citation: Front Genet. 2013 Jun 21;4:116
references.pmid: 23802013
references.citation: J Viral Hepat. 2013 Mar;20(3):158-66
references.pmid: 23383654
references.citation: Novartis Found Symp. 2006;277:23-39; discussion 40, 71-3, 251-3
references.pmid: 17319152
references.citation: Cell. 1993 Dec 3;75(5):843-54
references.pmid: 8252621
references.citation: Nucleic Acids Res. 2012 Mar;40(5):2181-96
references.pmid: 22080513
references.citation: Science. 2001 Oct 26;294(5543):853-8
references.pmid: 11679670
references.citation: J Virol. 2007 Nov;81(22):12218-26
references.pmid: 17855543
references.citation: Nat Rev Mol Cell Biol. 2009 Feb;10(2):116-25
references.pmid: 19165214
references.citation: Nat Rev Microbiol. 2013 Mar;11(3):169-80
references.pmid: 23411862
references.citation: Cell. 1993 Dec 3;75(5):855-62
references.pmid: 8252622
references.citation: J Infect Dis. 2011 Jun 15;203(12):1753-62
references.pmid: 21606534
references.citation: Proc Natl Acad Sci U S A. 2012 Jul 24;109(30):12117-22
references.pmid: 22778433
references.citation: RNA. 2012 Jul;18(7):1338-46
references.pmid: 22635403
references.citation: Mol Med Rep. 2013 Mar;7(3):791-8
references.pmid: 23354650
references.citation: Mol Cell. 2009 Jun 26;34(6):696-709
references.pmid: 19560422
references.citation: Cell Mol Life Sci. 2012 Aug;69(15):2621-33
references.pmid: 22391672
references.citation: J Virol. 2012 Mar;86(6):3244-52
references.pmid: 22205749
references.citation: Biochim Biophys Acta. 2011 Nov-Dec;1809(11-12):694-9
references.pmid: 21821155
references.citation: J Virol. 2008 Sep;82(18):9164-70
references.pmid: 18614632
references.citation: J Infect Dis. 2013 Sep 1;208(5):771-9
references.pmid: 23687223
references.citation: Hepatology. 2012 Nov;56(5):1631-40
references.pmid: 22610915
references.citation: Nat Rev Mol Cell Biol. 2012 Mar 22;13(4):239-50
references.pmid: 22436747
references.citation: Nat Immunol. 2013 Mar;14(3):205-10
references.pmid: 23416678
references.citation: PLoS Pathog. 2012 Jan;8(1):e1002465
references.pmid: 22241991
references.citation: PLoS Pathog. 2009 Feb;5(2):e1000299
references.pmid: 19214215
references.citation: mBio. 2013 Apr 16;4(2):e000193
references.pmid: 23592263
references.citation: Antiviral Res. 2010 Oct;88(1):119-23
references.pmid: 20637242
references.citation: Science. 2001 Oct 26;294(5543):858-62
references.pmid: 11679671
references.citation: Biomaterials. 2013 Sep;34(27):6429-43
references.pmid: 23727262
references.citation: Proc Natl Acad Sci U S A. 2013 Jan 29;110(5):1881-6
references.pmid: 23248316
references.citation: Leukemia. 2012 Mar;26(3):404-13
references.pmid: 22182919
references.citation: Front Genet. 2013 Jun 26;4:121
references.pmid: 23805154
references.citation: J Hepatol. 2009 Mar;50(3):453-60
references.pmid: 19144437
references.citation: Curr Opin Cell Biol. 2009 Jun;21(3):452-60
references.pmid: 19450959
references.citation: PLoS One. 2013 Jun 21;8(6):e66796
references.pmid: 23805279
references.citation: PLoS Pathog. 2010 Mar 19;6(3):e1000820
references.pmid: 20333250
references.citation: Virol J. 2012 Jun 12;9:109
references.pmid: 22691570
references.citation: J Virol. 2012 Dec;86(24):13486-500
references.pmid: 23035235
references.citation: Cancer Res. 2012 Dec 15;72(24):6333-7
references.pmid: 23222301
references.citation: PLoS Pathog. 2008 Jul 04;4(7):e1000098
references.pmid: 18604274
references.citation: Cell. 2009 Jan 23;136(2):215-33
references.pmid: 19167326
references.citation: Biochem Biophys Res Commun. 2010 Jun 4;396(3):596-601
references.pmid: 20412785
references.citation: PLoS Pathog. 2012 Dec;8(12):e1003018
references.pmid: 23308061
references.citation: Biochem Biophys Res Commun. 2012 Aug 31;425(3):662-7
references.pmid: 22850539
references.citation: Cell Host Microbe. 2013 Jun 12;13(6):678-90
references.pmid: 23768492
references.citation: Science. 2009 Nov 27;326(5957):1275-9
references.pmid: 19965479
references.citation: Am J Gastroenterol. 2011 Sep;106(9):1663-9
references.pmid: 21606975
references.citation: Science. 2010 Jan 8;327(5962):198-201
references.pmid: 19965718
references.citation: Retrovirology. 2008 Dec 29;5:118
references.pmid: 19114009
references.citation: Nature. 2003 Sep 25;425(6956):415-9
references.pmid: 14508493
references.citation: Cell Mol Life Sci. 2013 Dec;70(23):4631-44
references.pmid: 23811937
references.citation: Virology. 2011 Mar 15;411(2):325-43
references.pmid: 21277611
references.citation: Hepatology. 2013 Sep;58(3):863-71
references.pmid: 23390075
references.citation: Nat Struct Mol Biol. 2011 Mar;18(3):323-7
references.pmid: 21297638
references.citation: Nature. 2011 Aug 24;476(7361):450-3
references.pmid: 21866159
references.citation: RNA. 2011 Aug;17(8):1511-28
references.pmid: 21712399
references.citation: Nat Rev Genet. 2007 Feb;8(2):93-103
references.pmid: 17230196
references.citation: Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):3077-82
references.pmid: 22308400
references.citation: Curr Top Microbiol Immunol. 2004;283:121-43
references.pmid: 15298169
references.citation: Nature. 2005 Jun 2;435(7042):682-6
references.pmid: 15931223
references.citation: Antivir Ther. 2011;16(1):51-8
references.pmid: 21311108
references.citation: RNA. 2010 Nov;16(11):2068-74
references.pmid: 20841420
references.citation: Viruses. 2012 Sep;4(9):1390-409
references.pmid: 23170164
references.citation: Nucleic Acids Res. 2012 May;40(10):4626-40
references.pmid: 22270084
references.citation: RNA Biol. 2013 Feb;10(2):169-74
references.pmid: 23296026
references.citation: Viruses. 2012 Oct 26;4(11):2485-513
references.pmid: 23202492
references.citation: Adv Exp Med Biol. 2009;666:49-63
references.pmid: 20054974
references.citation: J Virol. 2004 Dec;78(23):12868-76
references.pmid: 15542639
references.citation: EMBO J. 2012 May 2;31(9):2207-21
references.pmid: 22473208
references.citation: Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11519-24
references.pmid: 20534531
references.citation: RNA. 2012 Nov;18(11):2041-55
references.pmid: 23019594
references.citation: RNA Biol. 2013 Jun;10(6):919-23
references.pmid: 23770926
references.citation: J Virol. 2012 Sep;86(18):10221-5
references.pmid: 22787204
references.citation: AIDS. 2002;16 Suppl 4:S17-23
references.pmid: 12698995
references.citation: Mol Ther. 2013 Oct;21(10):1898-908
references.pmid: 23765441
references.citation: J Infect. 2013 Oct;67(4):329-41
references.pmid: 23685241
references.citation: N Engl J Med. 2013 May 2;368(18):1685-94
references.pmid: 23534542
references.citation: Nat Neurosci. 2012 Jun;15(6):827-35
references.pmid: 22610069
references.citation: Trends Microbiol. 2009 Dec;17(12):544-53
references.pmid: 19828316
references.citation: Front Microbiol. 2012 Aug 24;3:306
references.pmid: 22936931
references.citation: PLoS Pathog. 2009 Jan;5(1):e1000263
references.pmid: 19148268
references.citation: Int J Biochem Cell Biol. 2009 Mar;41(3):451-4
references.pmid: 18761423
references.citation: J Gen Virol. 2013 May;94(Pt 5):985-995
references.pmid: 23343627
references.citation: EMBO J. 1998 Dec 1;17(23):7056-65
references.pmid: 9843510
references.citation: RNA. 2011 Feb;17(2):312-26
references.pmid: 21177881
references.citation: Science. 2007 Jul 20;317(5836):376-81
references.pmid: 17641203
references.citation: Virulence. 2010 Sep-Oct;1(5):433-5
references.pmid: 21170300
references.citation: Nature. 2008 Sep 4;455(7209):64-71
references.pmid: 18668037
references.citation: Sci Rep. 2013;3:1555
references.pmid: 23549102
references.citation: PLoS Pathog. 2010 Feb 12;6(2):e1000764
references.pmid: 20169186
references.citation: N Engl J Med. 2013 Apr 18;368(16):1509-1518
references.pmid: 23527958
references.citation: Biol Chem. 2012 Jul;393(7):599-604
references.pmid: 22944664
references.citation: EMBO Rep. 2012 Aug;13(8):716-23
references.pmid: 22677978
references.citation: J Urol. 2012 Apr;187(4):1466-72
references.pmid: 22341810
references.citation: J Immunol. 2009 Aug 1;183(3):2150-8
references.pmid: 19596990
references.citation: Nucleic Acids Res. 2010 Jan;38(3):750-63
references.pmid: 19933264
references.citation: PLoS One. 2011;6(10):e26971
references.pmid: 22066022
references.citation: Curr Opin Cell Biol. 2013 Apr;25(2):200-7
references.pmid: 23434068
references.citation: Nat Biotechnol. 2009 Jun;27(6):572-6
references.pmid: 19483680
references.citation: J Biol Chem. 2012 Nov 30;287(49):40884-90
references.pmid: 23043098
references.citation: BMC Bioinformatics. 2010 May 13;11:249
references.pmid: 20465802
references.citation: J Virol. 2011 Feb;85(4):1464-72
references.pmid: 21123372
references.citation: PLoS One. 2013;8(2):e56272
references.pmid: 23405269
references.citation: AIDS. 2012 Jul 17;26(11):1325-34
references.pmid: 22382145