Skip to main content
Top
Published in: Virology Journal 1/2013

Open Access 01-12-2013 | Research

The effects of hepatitis C virus core protein on the expression of miR-122 in vitro

Authors: Sujuan Li, Xiaokang Xing, Qiao Yang, Hangdi Xu, Jiliang He, Zhi Chen, Haihong Zhu

Published in: Virology Journal | Issue 1/2013

Login to get access

Abstract

Background

Hepatitis C virus (HCV) is one of the major pathogens of liver diseases. Some studies have previously reported that miR-122 can stimulate replication or translation of HCV. However, the effects of HCV infection on miR-122 expression are not clear. The aim of this study was to investigate the effects of HCV core protein on the expression of miR-122 in a cell culture model.

Results

The miR-122 levels in Huh7.5.1 cells infected with HCV for different days or different HCV abundance were measured by real-time PCR. Significant decrease of miR-122 expression was found at late stage of infection and in the high-abundance group. Huh7.5.1 cells transfected with plasmid pEGFP-core or pEGFP were used to detect the effects of HCV core protein on miR-122 expression, the results showed that core protein could down-regulate the miR-122 expression level in a time- and dose- dependent manner, and reduced the susceptibility of Huh7.5.1 cell to HCV.

Conclusions

Down-regulating miR-122 expression by HCV core protein may give a new insight into the interaction between HCV and miR-122 and chronic HCV infection.
Appendix
Available only for authorised users
Literature
1.
go back to reference Lauer GM, Walker BD: Hepatitis C virus infection. N Engl J Med 2001,345(1):41-52. 10.1056/NEJM200107053450107PubMedCrossRef Lauer GM, Walker BD: Hepatitis C virus infection. N Engl J Med 2001,345(1):41-52. 10.1056/NEJM200107053450107PubMedCrossRef
2.
go back to reference Rehermann B, Nascimbeni M: Immunology of hepatitis B virus and hepatitis C virus infection. Nat Rev Immunol 2005,5(3):215-229. 10.1038/nri1573PubMedCrossRef Rehermann B, Nascimbeni M: Immunology of hepatitis B virus and hepatitis C virus infection. Nat Rev Immunol 2005,5(3):215-229. 10.1038/nri1573PubMedCrossRef
3.
go back to reference Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL Jr, Häussinger D, Diago M, Carosi G, Dhumeaux D, Craxi A, Lin A, Hoffman J, Yu J: Peginterferon alfa-2a plus ribavirin for chronic hepatitis c virus infection. N Engl J Med 2002,347(13):975-982. 10.1056/NEJMoa020047PubMedCrossRef Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL Jr, Häussinger D, Diago M, Carosi G, Dhumeaux D, Craxi A, Lin A, Hoffman J, Yu J: Peginterferon alfa-2a plus ribavirin for chronic hepatitis c virus infection. N Engl J Med 2002,347(13):975-982. 10.1056/NEJMoa020047PubMedCrossRef
4.
go back to reference Hadziyannis SJ, Sette H Jr, Morgan TR, Balan V, Diago M, Marcellin P, Ramadori G, Bodenheimer H Jr, Bernstein D, Rizzetto M, Zeuzem S, Pockros PJ, Lin A, Ackrill AM, PEGASYS International Study Group: Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med 2004,140(5):346-355.PubMedCrossRef Hadziyannis SJ, Sette H Jr, Morgan TR, Balan V, Diago M, Marcellin P, Ramadori G, Bodenheimer H Jr, Bernstein D, Rizzetto M, Zeuzem S, Pockros PJ, Lin A, Ackrill AM, PEGASYS International Study Group: Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med 2004,140(5):346-355.PubMedCrossRef
5.
go back to reference Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, Koury K, Ling M, Albrecht JK: Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001,358(9286):958-965. 10.1016/S0140-6736(01)06102-5PubMedCrossRef Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, Koury K, Ling M, Albrecht JK: Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001,358(9286):958-965. 10.1016/S0140-6736(01)06102-5PubMedCrossRef
6.
go back to reference Poordad F, McCone J Jr, Bacon BR, Bruno S, Manns MP, Sulkowski MS, Jacobson IM, Reddy KR, Goodman ZD, Boparai N, DiNubile MJ, Sniukiene V, Brass CA, Albrecht JK, Bronowicki JP, SPRINT-2 Investigators: Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med 2011,364(13):1195-1206. 10.1056/NEJMoa1010494PubMedPubMedCentralCrossRef Poordad F, McCone J Jr, Bacon BR, Bruno S, Manns MP, Sulkowski MS, Jacobson IM, Reddy KR, Goodman ZD, Boparai N, DiNubile MJ, Sniukiene V, Brass CA, Albrecht JK, Bronowicki JP, SPRINT-2 Investigators: Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med 2011,364(13):1195-1206. 10.1056/NEJMoa1010494PubMedPubMedCentralCrossRef
7.
go back to reference Bacon BR, Gordon SC, Lawitz E, Marcellin P, Vierling JM, Zeuzem S, Poordad F, Goodman ZD, Sings HL, Boparai N, Burroughs M, Brass CA, Albrecht JK, Esteban R, HCV RESPOND-2 Investigators: Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med 2011,364(13):1207-1217. 10.1056/NEJMoa1009482PubMedPubMedCentralCrossRef Bacon BR, Gordon SC, Lawitz E, Marcellin P, Vierling JM, Zeuzem S, Poordad F, Goodman ZD, Sings HL, Boparai N, Burroughs M, Brass CA, Albrecht JK, Esteban R, HCV RESPOND-2 Investigators: Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med 2011,364(13):1207-1217. 10.1056/NEJMoa1009482PubMedPubMedCentralCrossRef
8.
go back to reference Jacobson IM, McHutchison JG, Dscheiko G, Di Bisceglie AM, Reddy KR, Bzowej NH, Marcellin P, Muir AJ, Ferenci P, Flisiak R, George J, Rizzeto M, Shouval D, Sola R, Terg RA, Yoshida EM, Adda N, Bengtsson L, Sankoh AJ, Kieffer TL, George S, Kauffman RS, Zeuzem S, ADVANCE Study Team: Telaprevir for previously untreated chronic hepatitis C virus infetion. N Engl J Med 2011,364(25):2405-2416. 10.1056/NEJMoa1012912PubMedCrossRef Jacobson IM, McHutchison JG, Dscheiko G, Di Bisceglie AM, Reddy KR, Bzowej NH, Marcellin P, Muir AJ, Ferenci P, Flisiak R, George J, Rizzeto M, Shouval D, Sola R, Terg RA, Yoshida EM, Adda N, Bengtsson L, Sankoh AJ, Kieffer TL, George S, Kauffman RS, Zeuzem S, ADVANCE Study Team: Telaprevir for previously untreated chronic hepatitis C virus infetion. N Engl J Med 2011,364(25):2405-2416. 10.1056/NEJMoa1012912PubMedCrossRef
9.
go back to reference Zeuzem S, Andreone P, Pol S, Lawitz E, Diago M, Roberts S, Focaccia R, Younossi Z, Foster GR, Hrban A, Ferenci P, Nevens F, Müllhaupt B, Pockros P, Terg R, Shouval D, Van Hoek B, Weiland O, Van Heeswijk R, De Meyer S, Luo D, Boogaerts G, Polo R, Picchio G, Beumont M, REALIZE Study Team: Telaprevir for retreatment of HCV infetion. N Engl J Med 2011,364(25):2417-2428. 10.1056/NEJMoa1013086PubMedCrossRef Zeuzem S, Andreone P, Pol S, Lawitz E, Diago M, Roberts S, Focaccia R, Younossi Z, Foster GR, Hrban A, Ferenci P, Nevens F, Müllhaupt B, Pockros P, Terg R, Shouval D, Van Hoek B, Weiland O, Van Heeswijk R, De Meyer S, Luo D, Boogaerts G, Polo R, Picchio G, Beumont M, REALIZE Study Team: Telaprevir for retreatment of HCV infetion. N Engl J Med 2011,364(25):2417-2428. 10.1056/NEJMoa1013086PubMedCrossRef
10.
go back to reference Inhof I, Simmonds P: Genotype differences in susceptibility and resistance development of hepatitis C virus to protease inhibitors telaprevir (VX-950) and danoprevir (ITMN-191). Hepatology 2011,53(4):1090-1099. 10.1002/hep.24172CrossRef Inhof I, Simmonds P: Genotype differences in susceptibility and resistance development of hepatitis C virus to protease inhibitors telaprevir (VX-950) and danoprevir (ITMN-191). Hepatology 2011,53(4):1090-1099. 10.1002/hep.24172CrossRef
11.
go back to reference Flamm SL: Chronic hepatitis C virus infection. JAMA 2003,289(18):2413-2417. 10.1001/jama.289.18.2413PubMedCrossRef Flamm SL: Chronic hepatitis C virus infection. JAMA 2003,289(18):2413-2417. 10.1001/jama.289.18.2413PubMedCrossRef
12.
go back to reference Melen K, Fagerlund R, Nyqvist M, Keskinen P, Julkunen I: Expression of hepatitis C virus core protein inhibits interferon-induced nuclear import of STATs. J Med Virol 2004,73(4):536-547. 10.1002/jmv.20123PubMedCrossRef Melen K, Fagerlund R, Nyqvist M, Keskinen P, Julkunen I: Expression of hepatitis C virus core protein inhibits interferon-induced nuclear import of STATs. J Med Virol 2004,73(4):536-547. 10.1002/jmv.20123PubMedCrossRef
13.
go back to reference Miller K, McArdle S, Gale MJ Jr, Geller DA, Tenoever B, Hiscott J, Gretch DR, Polyak SJ: Effects of the hepatitis C virus core protein on innate cellular defense pathways. J Interferon Cytokine Res 2004,24(7):391-402. 10.1089/1079990041535647PubMedCrossRef Miller K, McArdle S, Gale MJ Jr, Geller DA, Tenoever B, Hiscott J, Gretch DR, Polyak SJ: Effects of the hepatitis C virus core protein on innate cellular defense pathways. J Interferon Cytokine Res 2004,24(7):391-402. 10.1089/1079990041535647PubMedCrossRef
14.
go back to reference Taylor DR, Shi ST, Romano PR, Barber GN, Lai MM: Inhibition of the interferon-inducible protein kinase PKR by HCV E2 protein. Science 1999,285(5424):107-110. 10.1126/science.285.5424.107PubMedCrossRef Taylor DR, Shi ST, Romano PR, Barber GN, Lai MM: Inhibition of the interferon-inducible protein kinase PKR by HCV E2 protein. Science 1999,285(5424):107-110. 10.1126/science.285.5424.107PubMedCrossRef
15.
go back to reference Li K, Foy E, Ferreon JC, Nakamura M, Ferreon AC, Ikeda M, Ray SC, Gale M Jr, Lemon SM: Immune evasion by hepatitis C virus NS3/4A protease-mediated cleavage of the Toll-like receptor 3 adaptor protein TRIF. Proc Natl Acad Sci USA 2005,102(8):2992-2997. 10.1073/pnas.0408824102PubMedPubMedCentralCrossRef Li K, Foy E, Ferreon JC, Nakamura M, Ferreon AC, Ikeda M, Ray SC, Gale M Jr, Lemon SM: Immune evasion by hepatitis C virus NS3/4A protease-mediated cleavage of the Toll-like receptor 3 adaptor protein TRIF. Proc Natl Acad Sci USA 2005,102(8):2992-2997. 10.1073/pnas.0408824102PubMedPubMedCentralCrossRef
16.
go back to reference Li XD, Sun L, Seth RB, Pineda G, Chen ZJ: Hepatitis C virus protease NS3/4A mitochondrial antiviral signaling protein off the mitochondria to evade innate immunity. Proc Natl Acad Sci USA 2005,102(49):17717-17722. 10.1073/pnas.0508531102PubMedPubMedCentralCrossRef Li XD, Sun L, Seth RB, Pineda G, Chen ZJ: Hepatitis C virus protease NS3/4A mitochondrial antiviral signaling protein off the mitochondria to evade innate immunity. Proc Natl Acad Sci USA 2005,102(49):17717-17722. 10.1073/pnas.0508531102PubMedPubMedCentralCrossRef
17.
go back to reference Song J, Fujii M, Wang F, Itoh M, Hotta H: The NS5A protein of hepatitis C virus partially inhibits the antiviral activity of interferon. J Gen Virol 1999,80(Pt 4):879-886.PubMedCrossRef Song J, Fujii M, Wang F, Itoh M, Hotta H: The NS5A protein of hepatitis C virus partially inhibits the antiviral activity of interferon. J Gen Virol 1999,80(Pt 4):879-886.PubMedCrossRef
18.
go back to reference Chang J, Nicolas E, Marks D, Sander C, Lerro A, Buendia MA, Xu C, Mason WS, Moloshok T, Bort R, Zaret KS, Taylor JM: miR-122, a mammalian liver-specific microRNA, is processed from hcr mRNA and may downregulate the high affinity cationic amino acid transporter CAT-1. RNA Biol 2004,1(2):106-113. 10.4161/rna.1.2.1066PubMedCrossRef Chang J, Nicolas E, Marks D, Sander C, Lerro A, Buendia MA, Xu C, Mason WS, Moloshok T, Bort R, Zaret KS, Taylor JM: miR-122, a mammalian liver-specific microRNA, is processed from hcr mRNA and may downregulate the high affinity cationic amino acid transporter CAT-1. RNA Biol 2004,1(2):106-113. 10.4161/rna.1.2.1066PubMedCrossRef
19.
go back to reference Jopling CL, Yi M, Lancaster AM, Lemon SM, Sarnow P: Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science 2005,309(5740):1577-1581. 10.1126/science.1113329PubMedCrossRef Jopling CL, Yi M, Lancaster AM, Lemon SM, Sarnow P: Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science 2005,309(5740):1577-1581. 10.1126/science.1113329PubMedCrossRef
20.
go back to reference Henke JI, Goergen D, Zheng J, Song Y, Schϋttler CG, Fehr C, Jϋnemann C, Niepmann M: microRNA-122 stimulates translation of hepatitis C virus RNA. EMBO J 2008,27(24):3300-3310. 10.1038/emboj.2008.244PubMedPubMedCentralCrossRef Henke JI, Goergen D, Zheng J, Song Y, Schϋttler CG, Fehr C, Jϋnemann C, Niepmann M: microRNA-122 stimulates translation of hepatitis C virus RNA. EMBO J 2008,27(24):3300-3310. 10.1038/emboj.2008.244PubMedPubMedCentralCrossRef
21.
go back to reference Shan Y, Zheng J, Lambrecht RW, Bonkovsky HL: Reciprocal effects of micro-RNA-122 on expression of heme oxygenase-1 and hepatitis C virus genes in human hepatocytes. Gastroenterology 2007,133(4):1166-1174. 10.1053/j.gastro.2007.08.002PubMedPubMedCentralCrossRef Shan Y, Zheng J, Lambrecht RW, Bonkovsky HL: Reciprocal effects of micro-RNA-122 on expression of heme oxygenase-1 and hepatitis C virus genes in human hepatocytes. Gastroenterology 2007,133(4):1166-1174. 10.1053/j.gastro.2007.08.002PubMedPubMedCentralCrossRef
22.
go back to reference Cermelli S, Ruggieri A, Marrero JA, Ioannou GN, Beretta L: Circulating microRNAs in patients with chronic hepatitis C and non-alcoholic fatty liver disease. PLoS One 2011,6(8):e23937. 10.1371/journal.pone.0023937PubMedPubMedCentralCrossRef Cermelli S, Ruggieri A, Marrero JA, Ioannou GN, Beretta L: Circulating microRNAs in patients with chronic hepatitis C and non-alcoholic fatty liver disease. PLoS One 2011,6(8):e23937. 10.1371/journal.pone.0023937PubMedPubMedCentralCrossRef
23.
go back to reference Randall G, Panis M, Cooper JD, Tellinghuisen TL, Sukhodolets KE, Pfeffer S, Landthaler M, Landgraf P, Kan S, Lindenbach BD, Chien M, Weir DB, Russo JJ, Ju J, Brownstein MJ, Sheridan R, Sander C, Zavolan M, Tuschl T, Rice CM: Cellular cofactors affecting hepatitis C virus infection and replication. Proc Natl Acad Sci USA 2007,104(31):12884-12889. 10.1073/pnas.0704894104PubMedPubMedCentralCrossRef Randall G, Panis M, Cooper JD, Tellinghuisen TL, Sukhodolets KE, Pfeffer S, Landthaler M, Landgraf P, Kan S, Lindenbach BD, Chien M, Weir DB, Russo JJ, Ju J, Brownstein MJ, Sheridan R, Sander C, Zavolan M, Tuschl T, Rice CM: Cellular cofactors affecting hepatitis C virus infection and replication. Proc Natl Acad Sci USA 2007,104(31):12884-12889. 10.1073/pnas.0704894104PubMedPubMedCentralCrossRef
24.
go back to reference Marquez RT, Bandyopadhyay S, Wendlandt EB, Keck K, Hoffer BA, Icardi MS, Christensen RN, Schmidt WN, McCaffrey AP: Correlation between microRNA expression levels and clinical parameters associated with chronic hepatitis C viral infection in humans. Lab Invest 2010,90(12):1727-1736. 10.1038/labinvest.2010.126PubMedCrossRef Marquez RT, Bandyopadhyay S, Wendlandt EB, Keck K, Hoffer BA, Icardi MS, Christensen RN, Schmidt WN, McCaffrey AP: Correlation between microRNA expression levels and clinical parameters associated with chronic hepatitis C viral infection in humans. Lab Invest 2010,90(12):1727-1736. 10.1038/labinvest.2010.126PubMedCrossRef
25.
go back to reference Sarasin-Filipowicz M, Krol J, Markiewicz I, Heim MH, Filipowicz W: Decreased levels of microRNA miR-122 in individuals with hepatitis C responding poorly to interferon therapy. Nat Med 2009,15(1):31-33. 10.1038/nm.1902PubMedCrossRef Sarasin-Filipowicz M, Krol J, Markiewicz I, Heim MH, Filipowicz W: Decreased levels of microRNA miR-122 in individuals with hepatitis C responding poorly to interferon therapy. Nat Med 2009,15(1):31-33. 10.1038/nm.1902PubMedCrossRef
26.
go back to reference Morita K, Taketomi A, Shirabe K, Umeda K, Kayashima H, Ninomiya M, Uchiyama H, Soejima Y, Maehara Y: Clinical significance and potential of hepatic microRNA-122 expression in hepatitis C. Liver Int 2011,31(4):474-484. 10.1111/j.1478-3231.2010.02433.xPubMedCrossRef Morita K, Taketomi A, Shirabe K, Umeda K, Kayashima H, Ninomiya M, Uchiyama H, Soejima Y, Maehara Y: Clinical significance and potential of hepatic microRNA-122 expression in hepatitis C. Liver Int 2011,31(4):474-484. 10.1111/j.1478-3231.2010.02433.xPubMedCrossRef
27.
go back to reference Sallie R: Replicative homeostasis: a mechanism of viral persistence. Med Hypotheses 2004,63(3):515-523. 10.1016/j.mehy.2004.02.050PubMedCrossRef Sallie R: Replicative homeostasis: a mechanism of viral persistence. Med Hypotheses 2004,63(3):515-523. 10.1016/j.mehy.2004.02.050PubMedCrossRef
28.
go back to reference Sallie R: Replicative homeostasis: a fundamental mechanism mediating selective viral replication and escape mutation. Virol J 2005, 2: 10. 10.1186/1743-422X-2-10PubMedPubMedCentralCrossRef Sallie R: Replicative homeostasis: a fundamental mechanism mediating selective viral replication and escape mutation. Virol J 2005, 2: 10. 10.1186/1743-422X-2-10PubMedPubMedCentralCrossRef
29.
go back to reference Sallie R: Replicative homeostasis II: influence of polymerase fidelity on RNA virus quasispecies biology: implications for immune recognition, viral autoimmunity and other "virus receptor" diseases. Virol J 2005, 2: 70. 10.1186/1743-422X-2-70PubMedPubMedCentralCrossRef Sallie R: Replicative homeostasis II: influence of polymerase fidelity on RNA virus quasispecies biology: implications for immune recognition, viral autoimmunity and other "virus receptor" diseases. Virol J 2005, 2: 70. 10.1186/1743-422X-2-70PubMedPubMedCentralCrossRef
30.
go back to reference Sallie R: Replicative homeostasis III: implications for antiviral therapy and mechanisms of response and non-response. Virol J 2007, 4: 29. 10.1186/1743-422X-4-29PubMedPubMedCentralCrossRef Sallie R: Replicative homeostasis III: implications for antiviral therapy and mechanisms of response and non-response. Virol J 2007, 4: 29. 10.1186/1743-422X-4-29PubMedPubMedCentralCrossRef
Metadata
Title
The effects of hepatitis C virus core protein on the expression of miR-122 in vitro
Authors
Sujuan Li
Xiaokang Xing
Qiao Yang
Hangdi Xu
Jiliang He
Zhi Chen
Haihong Zhu
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2013
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/1743-422X-10-98

Other articles of this Issue 1/2013

Virology Journal 1/2013 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.