title: Interaction of host cell microRNAs with the HCV RNA genome during infection of liver cells.
abstract: It has remained an enigma how hepatitis C viral (HCV) RNA can persist in the liver of infected patients for many decades. With the recent discovery of roles for microRNAs in gene expression, it was reported that the HCV RNA genome subverts liver-specific microRNA miR-122 to protect its 5' end from degradation by host cell exoribonucleases. Sequestration of miR-122 in cultured liver cells and in the liver of chimpanzees by small, modified antisense RNAs resulted in dramatic loss of HCV RNA and viral yield. This finding led to the first successful human trial in which subcutaneous administration of antisense molecules against miR-122 lowered viral yield in HCV patients, without the emergence of resistant virus. In this review, the authors summarize the molecular mechanism by which miR-122 protects the HCV RNA genome from degradation by exoribonucleases Xrn1 and Xrn2 and discuss the application of miR-122 antisense molecules in the clinic.
authors: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California.
authors: Cecilia D
authors: CD
authors: Sedano
authors: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California.
authors: Peter
authors: P
authors: Sarnow
mesh_terms: D005095:Exoribonucleases / Q000378:metabolism; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000235:genetics* / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism*; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism*; D014779:Virus Replication
chemical_list: C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D012367:RNA, Viral; D005095:Exoribonucleases
references: Gene. 1990 Oct 30;95(1):85-90
references: 1979303
references: Nature. 2004 Nov 25;432(7016):517-22
references: 15565157
references: J Biol Chem. 1994 May 13;269(19):14094-102
references: 8188690
references: Mol Cell Biol. 1995 May;15(5):2728-36
references: 7739553
references: J Cell Biol. 1997 Feb 24;136(4):761-73
references: 9049243
references: Mol Cell Biol. 1997 Oct;17(10):6122-30
references: 9315672
references: Biochem Soc Trans. 2008 Dec;36(Pt 6):1224-31
references: 19021530
references: Nucleic Acids Res. 2009 Jan;37(Database issue):D111-7
references: 18927110
references: EMBO J. 2008 Dec 17;27(24):3300-10
references: 19020517
references: J Hepatol. 2009 Mar;50(3):453-60
references: 19144437
references: Proc Natl Acad Sci U S A. 2009 Aug 11;106(32):13517-22
references: 19628699
references: Nature. 2009 Sep 24;461(7263):546-9
references: 19734881
references: J Gen Virol. 2010 Sep;91(Pt 9):2238-48
references: 20505011
references: Clin Microbiol Infect. 2011 Feb;17(2):107-15
references: 21091831
references: J Virol. 2011 Mar;85(5):2342-50
references: 21177824
references: Trends Microbiol. 2011 Feb;19(2):95-103
references: 21146993
references: Proc Natl Acad Sci U S A. 2011 Feb 22;108(8):3193-8
references: 21220300
references: Nat Struct Mol Biol. 2011 Mar;18(3):270-6
references: 21297639
references: J Virol. 2011 Jul;85(14):6882-92
references: 21543503
references: Genes Dev. 2011 Sep 15;25(18):1881-94
references: 21896651
references: Nucleic Acids Res. 2011 Sep 1;39(17):7716-29
references: 21653556
references: Proc Natl Acad Sci U S A. 2012 Jan 17;109(3):941-6
references: 22215596
references: Science. 2012 Apr 13;336(6078):237-40
references: 22499947
references: Mol Cell. 2012 May 11;46(3):311-24
references: 22483619
references: Cell Mol Life Sci. 2012 Aug;69(15):2621-33
references: 22391672
references: J Clin Invest. 2012 Aug;122(8):2871-83
references: 22820288
references: Cell. 2005 Jul 15;122(1):9-12
references: 16009127
references: Nature. 2004 Nov 25;432(7016):522-5
references: 15565158
references: J Clin Invest. 2012 Aug;122(8):2884-97
references: 22820290
references: Science. 2005 Sep 2;309(5740):1577-81
references: 16141076
references: Nature. 2005 Dec 1;438(7068):685-9
references: 16258535
references: Cell Metab. 2006 Feb;3(2):87-98
references: 16459310
references: Nat Rev Cancer. 2006 Apr;6(4):259-69
references: 16557279
references: RNA. 2006 Dec;12(12):2171-86
references: 17077271
references: RNA Biol. 2004 Jul;1(2):106-13
references: 17179747
references: Nature. 2007 Oct 18;449(7164):919-22
references: 17943132
references: Nature. 2008 Apr 17;452(7189):896-9
references: 18368051
references: Virology. 2012 Nov 25;433(2):479-88
references: 22999255
references: Virology. 2013 Jan 20;435(2):472-84
references: 23141719
references: Proc Natl Acad Sci U S A. 2013 Jan 29;110(5):1881-6
references: 23248316
references: PLoS One. 2013;8(2):e56709
references: 23437218
references: Science. 2013 Apr 5;340(6128):82-5
references: 23559250
references: Curr Opin Gastroenterol. 2013 May;29(3):243-9
references: 23563981
references: N Engl J Med. 2013 May 2;368(18):1685-94
references: 23534542
references: PLoS One. 2013;8(6):e65064
references: 23798998
references: J Biol Chem. 2013 Jul 5;288(27):19750-9
references: 23689372
references: RNA. 2013 Dec;19(12):1825-32
references: 24106328
references: Mol Cell. 2014 Jun 5;54(5):737-50
references: 24768540
references: Cell Host Microbe. 2014 Aug 13;16(2):257-64
references: 25121753
references: Cell Cycle. 2008 Mar 15;7(6):759-64
references: 18344688
references: Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13985-90
references: 11106401
references: Science. 2001 Oct 26;294(5543):853-8
references: 11679670
references: J Virol. 2001 Dec;75(24):12047-57
references: 11711595
references: EMBO J. 2002 Sep 2;21(17):4663-70
references: 12198168
references: Hepatology. 2002 Nov;36(5 Suppl 1):S21-9
references: 12407573
references: Cell. 2003 Dec 26;115(7):787-98
references: 14697198
references: Biochem Biophys Res Commun. 1978 Mar 30;81(2):656-61
references: 352351
references: J Biol Chem. 1980 Apr 10;255(7):3080-5
references: 6244307
references: Mol Cell Biol. 1998 Mar;18(3):1181-9
references: 9488433
references: Mech Dev. 1998 Dec;79(1-2):51-5
references: 10349620
references: Genes Dev. 1992 Jul;6(7):1173-89
references: 1628825