Abstract
Hepatitis C virus (HCV), a positive single-stranded RNA virus, is a major cause of liver disease in humans. Herein we report a novel strategy to inhibit the reproduction and translation of HCV using a short RNA, named an Additional RNA, to activate the endonuclease activity of Argonaute 2 (Ago2). In the presence of the Additional RNA, the HCV genome RNA has the requisite 12 nucleotides of base-pairing with microRNA-122. This activates the endonuclease activity of Ago2, resulting in cleavage and release of the HCV genome RNA from Ago2 and microRNA-122. The free HCV genome RNA would be susceptible to intracellular degradation, effectively inhibiting its reproduction and translation. This study presents a new method to inhibit HCV that may hold great potential for HCV treatment in the future.
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References
Khaliq S, Jahan S, Ijaz B, et al. Inhibition of hepatitis C virus genotype 3a by siRNAs targeting envelope genes. Arch Virol, 2011, 156: 433–442
Chevalier C, Saulnier A, Benureau Y, et al. Inhibition of hepatitis C virus infection in cell culture by small interfering RNAs. Mol Ther, 2007, 15: 1452–1462
Chang B, Lee C H, Lee J H, et al. Comparative analysis of intracellular inhibition of hepatitis C virus replication by small interfering RNAs. Biotechnol Lett, 2010, 32: 1231–1237
Clark V C, Peter J A, Nelson D R. New therapeutic strategies in HCV: second-generation protease inhibitors. Liver Int, 2013, 33(Suppl 1): 80–84
Ariumi Y, Kuroki M, Kushima Y, et al. Hepatitis C virus hijacks P-body and stress granule components around lipid droplets. J Virol, 2011, 85: 6882–6892
Jopling C L, Schutz S, Sarnow P. Position-dependent function for a tandem microRNA miR-122-binding site located in the hepatitis C virus RNA genome. Cell Host Microbe, 2008, 4: 77–85
Berezhna S Y, Supekova L, Sever M J, et al. Dual regulation of hepatitis C viral RNA by cellular RNAi requires partitioning of Ago2 to lipid droplets and P-bodies. RNA, 2011, 17: 1831–1845
Liu J, Carmell M A, Rivas F V, et al. Argonaute2 is the catalytic engine of mammalian RNAi. Science, 2004, 305: 1437–1441
Tan G S, Garchow B G, Liu X, et al. Expanded RNA-binding activities of mammalian Argonaute 2. Nucleic Acids Res, 2009, 37: 7533–7545
Rand T A, Ginalski K, Grishin N V, et al. Biochemical identification of Argonaute 2 as the sole protein required for RNA-induced silencing complex activity. Proc Natl Acad Sci USA, 2004, 101: 14385–14389
Liu Y, Tan H, Tian H, et al. Autoantigen La promotes efficient RNAi, antiviral response, and transposon silencing by facilitating multiple-turnover RISC catalysis. Mol Cell, 2011, 44: 502–508
Schirle N T, MacRae I J. The crystal structure of human Argonaute2. Science, 2012, 336: 1037–1040
Voinnet O. Origin, biogenesis, and activity of plant microRNAs. Cell, 2009, 136: 669–687
Shimakami T, Yamane D, Jangra R K, et al. Stabilization of hepatitis C virus RNA by an Ago2-miR-122 complex. Proc Natl Acad Sci USA, 2012, 109: 941–946
Young D D, Connelly C M, Grohmann C, et al. Small molecule modifiers of microRNA miR-122 function for the treatment of hepatitis C virus infection and hepatocellular carcinoma. J Am Chem Soc, 2010, 132: 7976–7981
Henke J I, Goergen D, Zheng J, et al. microRNA-122 stimulates translation of hepatitis C virus RNA. EMBO J, 2008, 27: 3300–3310
Lanford R E, Hildebrandt-Eriksen E S, Petri A, et al. Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science, 2010, 327: 198–201
Wilson J A, Zhang C, Huys A, et al. Human Ago2 is required for efficient microRNA 122 regulation of hepatitis C virus RNA accumulation and translation. J Virol, 2011, 85: 2342–2350
Yang N, Cao Y, Han P, et al. Tools for investigation of the RNA endonuclease activity of mammalian Argonaute2 protein. Anal Chem, 2012, 84: 2492–2497
Roberts A P, Lewis A P, Jopling C L. miR-122 activates hepatitis C virus translation by a specialized mechanism requiring particular RNA components. Nucleic Acids Res, 2011, 39: 7716–7729
Jopling C L, Yi M, Lancaster A M, et al. Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science, 2005, 309: 1577–1581
Yin H, Zhou Y, Zhang H, et al. Electrochemical determination of microRNA-21 based on graphene, LNA integrated molecular beacon, AuNPs and biotin multifunctional bio bar codes and enzymatic assay system. Biosens Bioelectron, 2012, 33: 247–253
Huntzinger E, Izaurralde E. Gene silencing by microRNAs: contributions of translational repression and mRNA decay. Nat Rev Genet, 2011, 12: 99–110
Hun X, Wang Z P. L-Argininamide biosensor based on S1 nuclease hydrolysis signal amplification. Microchim Acta, 2012, 176: 209–216
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Duan, A., Ning, L., Li, C. et al. A novel strategy to inhibit the reproduction and translation of hepatitis C virus. Sci. China Life Sci. 56, 293–297 (2013). https://doi.org/10.1007/s11427-013-4468-2
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DOI: https://doi.org/10.1007/s11427-013-4468-2