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BMC Immunology
Published in: BMC Immunology 1/2012

Open Access 01-12-2012 | Research article

The Tat protein of human immunodeficiency virus-1 enhances hepatitis C virus replication through interferon gamma-inducible protein-10

Authors: Jing Qu, Qi Zhang, Youxing Li, Weiyong Liu, Lvxiao Chen, Ying Zhu, Jianguo Wu

Published in: BMC Immunology | Issue 1/2012

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Abstract

Background

Co-infection with human immunodeficiency virus-1 (HIV-1) and hepatitis C virus (HCV) is associated with faster progression of liver disease and an increase in HCV persistence. However, the mechanism by which HIV-1 accelerates the progression of HCV liver disease remains unknown.

Results

HIV-1/HCV co-infection is associated with increased expression of interferon gamma-induced protein-10 (IP-10) mRNA in peripheral blood mononuclear cells (PBMCs). HCV RNA levels were higher in PBMCs of patients with HIV-1/HCV co-infection than in patients with HCV mono-infection. HIV-1 Tat and IP-10 activated HCV replication in a time-dependent manner, and HIV-1 Tat induced IP-10 production. In addition, the effect of HIV-1 Tat on HCV replication was blocked by anti-IP-10 monoclonal antibody, demonstrating that the effect of HIV-1 Tat on HCV replication depends on IP-10. Taken together, these results suggest that HIV-1 Tat protein activates HCV replication by upregulating IP-10 production.

Conclusions

HIV-1/HCV co-infection is associated with increased expression of IP-10 mRNA and replication of HCV RNA. Furthermore, both HIV-1 Tat and IP-10 activate HCV replication. HIV-1 Tat activates HCV replication by upregulating IP-10 production. These results expand our understanding of HIV-1 in HCV replication and the mechanism involved in the regulation of HCV replication mediated by HIV-1 during co-infection.
Appendix
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Literature
1.
Sherman KE, Rouster SD, Chung RT, Rajicic N: Hepatitis C Virus prevalence among patients infected with Human Immunodeficiency Virus: a cross-sectional analysis of the US adult AIDS Clinical Trials Group. Clin Infect Dis. 2002, 34: 831-837. 10.1086/339042.PubMedCrossRef
2.
Bonacini M, Louie S, Bzowej N, Wohl AR: Survival in patients with HIV infection and viral hepatitis B or C: a cohort study. AIDS. 2004, 18: 2039-2045. 10.1097/00002030-200410210-00008.PubMedCrossRef
3.
Benhamou Y, Bochet M, Di Martino V, Charlotte F, Azria F, Coutellier A, Vidaud M, Bricaire F, Opolon P, Katlama C: Liver fibrosis progression in human immunodeficiency virus and hepatitis C virus coinfected patients. The Multivirc Group. Hepatology. 1999, 30: 1054-1058. 10.1002/hep.510300409.PubMedCrossRef
4.
Macias J, Berenguer J, Japon MA, Giron JA, Rivero A, Lopez-Cortes LF, Moreno A, Gonzalez-Serrano M, Iribarren JA, Ortega E: Fast fibrosis progression between repeated liver biopsies in patients coinfected with human immunodeficiency virus/hepatitis C virus. Hepatology. 2009, 50: 1056-1063. 10.1002/hep.23136.PubMedCrossRef
5.
Thomas DL, Astemborski J, Rai RM, Anania FA, Schaeffer M, Galai N, Nolt K, Nelson KE, Strathdee SA, Johnson L: The natural history of hepatitis C virus infection: host, viral, and environmental factors. JAMA. 2000, 284: 450-456. 10.1001/jama.284.4.450.PubMedCrossRef
6.
Rey D, Fritsch S, Schmitt C, Meyer P, Lang JM, Stoll-Keller F: Quantitation of hepatitis C virus RNA in saliva and serum of patients coinfected with HCV and human immunodeficiency virus. J Med Virol. 2001, 63: 117-119. 10.1002/1096-9071(20000201)63:2<117::AID-JMV1005>3.0.CO;2-1.PubMedCrossRef
7.
Eyster ME, Fried MW, Di Bisceglie AM, Goedert JJ: Increasing hepatitis C virus RNA levels in hemophiliacs: relationship to human immunodeficiency virus infection and liver disease. Multicenter Hemophilia Cohort Study. Blood. 1994, 84: 1020-1023.PubMed
8.
Bare P, Massud I, Belmonte L, Corti M, Villafane M, Perez Bianco R, de Tezanos-pinto M, de Bracco MM, Ruibal-Ares B: HCV recovery from peripheral blood mononuclear cell culture supernatants derived from HCV-HIV co-infected haemophilic patients with undetectable HCV viraemia. Haemophilia. 2003, 9: 598-604. 10.1046/j.1365-2516.2003.00808.x.PubMedCrossRef
9.
Natarajan V, Kottilil S, Hazen A, Adelsberger J, Murphy AA, Polis MA, Kovacs JA: HCV in peripheral blood mononuclear cells are predominantly carried on the surface of cells in HIV/HCV co-infected individuals. J Med Virol. 2010, 82: 2032-7. 10.1002/jmv.21906.PubMedCrossRef
10.
Parodi C, Belmonte L, Bare P, de Bracco MM, Ruibal-Ares B: Impact of human immune deficiency virus infection on hepatitis C virus infection and replication. Curr HIV Res. 2007, 5: 55-67. 10.2174/157016207779316341.PubMedCrossRef
11.
Wilkinson J, Radkowski M, Laskus T: Hepatitis C virus neuroinvasion: identification of infected cells. J Virol. 2009, 83: 1312-1319. 10.1128/JVI.01890-08.PubMedPubMedCentralCrossRef
12.
Luster AD, Unkeless JC, Ravetch JV: Gamma-interferon transcriptionally regulates an early-response gene containing homology to platelet proteins. Nature. 1985, 315: 672-676. 10.1038/315672a0.PubMedCrossRef
13.
Taub DD, Lloyd AR, Conlon K, Wang JM, Ortaldo JR, Harada A, Matsushima K, Kelvin DJ, Oppenheim JJ: Recombinant human interferon-inducible protein 10 is a chemoattractant for human monocytes and T lymphocytes and promotes T cell adhesion to endothelial cells. J Exp Med. 1993, 177: 1809-1814. 10.1084/jem.177.6.1809.PubMedCrossRef
14.
Taub DD, Sayers TJ, Carter CR, Ortaldo JR: Alpha and beta chemokines induce NK cell migration and enhance NK-mediated cytolysis. J Immunol. 1995, 155: 3877-3888.PubMed
15.
Hua LL, Lee SC: Distinct patterns of stimulus-inducible chemokine mRNA accumulation in human fetal astrocytes and microglia. Glia. 2000, 30: 74-81. 10.1002/(SICI)1098-1136(200003)30:1<74::AID-GLIA8>3.0.CO;2-C.PubMedCrossRef
16.
Harvey CE, Post JJ, Palladinetti P, Freeman AJ, Ffrench RA, Kumar RK, Marinos G, Lloyd AR: Expression of the chemokine IP-10 (CXCL10) by hepatocytes in chronic hepatitis C virus infection correlates with histological severity and lobular inflammation. J Leukoc Biol. 2003, 74: 360-369. 10.1189/jlb.0303093.PubMedCrossRef
17.
Butera D, Marukian S, Iwamaye AE, Hembrador E, Chambers TJ, Di Bisceglie AM, Charles ED, Talal AH, Jacobson IM, Rice CM: Plasma chemokine levels correlate with the outcome of antiviral therapy in patients with hepatitis C. Blood. 2005, 106: 1175-1182. 10.1182/blood-2005-01-0126.PubMedPubMedCentralCrossRef
18.
Mihm S, Schweyer S, Ramadori G: Expression of the chemokine IP-10 correlates with the accumulation of hepatic IFN-gamma and IL-18 mRNA in chronic hepatitis C but not in hepatitis B. J Med Virol. 2003, 70: 562-570. 10.1002/jmv.10431.PubMedCrossRef
19.
Romero AI, Lagging M, Westin J, Dhillon AP, Dustin LB, Pawlotsky JM, Neumann AU, Ferrari C, Missale G, Haagmans BL: Interferon (IFN)-gamma-inducible protein-10: association with histological results, viral kinetics, and outcome during treatment with pegylated IFN-alpha 2a and ribavirin for chronic hepatitis C virus infection. J Infect Dis. 2006, 194: 895-903. 10.1086/507307.PubMedCrossRef
20.
Reiberger T, Aberle JH, Kundi M, Kohrgruber N, Rieger A, Gangl A, Holzmann H, Peck-Radosavljevic M: IP-10 correlates with hepatitis C viral load, hepatic inflammation and fibrosis and predicts hepatitis C virus relapse or non-response in HIV-HCV coinfection. Antivir Ther. 2008, 13: 969-976.PubMed
21.
Stylianou E, Aukrust P, Bendtzen K, Muller F, Froland SS: Interferons and interferon (IFN)-inducible protein 10 during highly active anti-retroviral therapy (HAART)-possible immunosuppressive role of IFN-alpha in HIV infection. Clin Exp Immunol. 2000, 119: 479-485. 10.1046/j.1365-2249.2000.01144.x.PubMedPubMedCentralCrossRef
22.
Kutsch O, Oh J, Nath A, Benveniste EN: Induction of the chemokines interleukin-8 and IP-10 by human immunodeficiency virus type 1 tat in astrocytes. J Virol. 2000, 74: 9214-9221. 10.1128/JVI.74.19.9214-9221.2000.PubMedPubMedCentralCrossRef
23.
Izmailova E, Bertley FM, Huang Q, Makori N, Miller CJ, Young RA, Aldovini A: HIV-1 Tat reprograms immature dendritic cells to express chemoattractants for activated T cells and macrophages. Nat Med. 2003, 9: 191-197. 10.1038/nm822.PubMedCrossRef
24.
Roe B, Coughlan S, Hassan J, Grogan A, Farrell G, Norris S, Bergin C, Hall WW: Elevated serum levels of interferon- gamma -inducible protein-10 in patients coinfected with hepatitis C virus and HIV. J Infect Dis. 2007, 196: 1053-1057. 10.1086/520935.PubMedCrossRef
25.
Dayton AI, Sodroski JG, Rosen CA, Goh WC, Haseltine WA: The trans-activator gene of the human T cell lymphotropic virus type III is required for replication. Cell. 1986, 44: 941-947. 10.1016/0092-8674(86)90017-6.PubMedCrossRef
26.
Ferrari A, Pellegrini V, Arcangeli C, Fittipaldi A, Giacca M, Beltram F: Caveolae-mediated internalization of extracellular HIV-1 tat fusion proteins visualized in real time. Mol Ther. 2003, 8: 284-294. 10.1016/S1525-0016(03)00122-9.PubMedCrossRef
27.
Nath A, Conant K, Chen P, Scott C, Major EO: Transient exposure to HIV-1 Tat protein results in cytokine production in macrophages and astrocytes. A hit and run phenomenon. J Biol Chem. 1999, 274: 17098-17102. 10.1074/jbc.274.24.17098.PubMedCrossRef
28.
Badou A, Bennasser Y, Moreau M, Leclerc C, Benkirane M, Bahraoui E: Tat protein of human immunodeficiency virus type 1 induces interleukin-10 in human peripheral blood monocytes: implication of protein kinase C-dependent pathway. J Virol. 2000, 74: 10551-10562. 10.1128/JVI.74.22.10551-10562.2000.PubMedPubMedCentralCrossRef
29.
Huang L, Bosch I, Hofmann W, Sodroski J, Pardee AB: Tat protein induces human immunodeficiency virus type 1 (HIV-1) coreceptors and promotes infection with both macrophage-tropic and T-lymphotropic HIV-1 strains. J Virol. 1998, 72: 8952-8960.PubMedPubMedCentral
30.
Stettner MR, Nance JA, Wright CA, Kinoshita Y, Kim WK, Morgello S, Rappaport J, Khalili K, Gordon J, Johnson EM: SMAD proteins of oligodendroglial cells regulate transcription of JC virus early and late genes coordinately with the Tat protein of human immunodeficiency virus type 1. J Gen Virol. 2009, 90: 2005-2014. 10.1099/vir.0.011072-0.PubMedPubMedCentralCrossRef
31.
Gorrill T, Feliciano M, Mukerjee R, Sawaya BE, Khalili K, White MK: Activation of early gene transcription in polyomavirus BK by human immunodeficiency virus type 1 Tat. J Gen Virol. 2006, 87: 1557-1566. 10.1099/vir.0.81569-0.PubMedCrossRef
32.
Nyagol J, Leucci E, Onnis A, De Falco G, Tigli C, Sanseverino F, Torriccelli M, Palummo N, Pacenti L, Santopietro R: The effects of HIV-1 Tat protein on cell cycle during cervical carcinogenesis. Cancer Biol Ther. 2006, 5: 684-690. 10.4161/cbt.5.6.2907.PubMedCrossRef
33.
Thomas DL, Shih JW, Alter HJ, Vlahov D, Cohn S, Hoover DR, Cheung L, Nelson KE: Effect of human immunodeficiency virus on hepatitis C virus infection among injecting drug users. J Infect Dis. 1996, 174: 690-695. 10.1093/infdis/174.4.690.PubMedCrossRef
34.
Beld M, Penning M, Lukashov V, McMorrow M, Roos M, Pakker N, van den Hoek A, Goudsmit J: Evidence that both HIV and HIV-induced immunodeficiency enhance HCV replication among HCV seroconverters. Virology. 1998, 244: 504-512. 10.1006/viro.1998.9130.PubMedCrossRef
35.
Zeremski M, Petrovic LM, Talal AH: The role of chemokines as inflammatory mediators in chronic hepatitis C virus infection. J Viral Hepat. 2007, 14: 675-687.PubMed
36.
Koo BC, McPoland P, Wagoner JP, Kane OJ, Lohmann V, Polyak SJ: Relationships between hepatitis C virus replication and CXCL-8 production in vitro. J Virol. 2006, 80: 7885-7893. 10.1128/JVI.00519-06.PubMedPubMedCentralCrossRef
37.
Wakita T, Pietschmann T, Kato T, Date T, Miyamoto M, Zhao Z, Murthy K, Habermann A, Krausslich HG, Mizokami M: Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nat Med. 2005, 11: 791-796. 10.1038/nm1268.PubMedPubMedCentralCrossRef
38.
Qu J, Yang Z, Zhang Q, Liu W, Li Y, Ding Q, Liu F, Liu Y, Pan Z, He B: Human immunodeficiency virus-1 Rev protein activates hepatitis C virus gene expression by directly targeting the HCV 5'-untranslated region. FEBS Lett. 2011, 585: 4002-9. 10.1016/j.febslet.2011.11.008.PubMedCrossRef
39.
Tedaldi EM, Baker RK, Moorman AC, Alzola CF, Furhrer J, McCabe RE, Wood KC, Holmberg SD: Influence of coinfection with hepatitis C virus on morbidity and mortality due to human immunodeficiency virus infection in the era of highly active antiretroviral therapy. Clin Infect Dis. 2003, 36: 363-367. 10.1086/345953.PubMedCrossRef
40.
Salmon-Ceron D, Lewden C, Morlat P, Bevilacqua S, Jougla E, Bonnet F, Heripret L, Costagliola D, May T, Chene G: Liver disease as a major cause of death among HIV infected patients: role of hepatitis C and B viruses and alcohol. J Hepatol. 2005, 42: 799-805. 10.1016/j.jhep.2005.01.022.PubMedCrossRef
41.
Lane BR, King SR, Bock PJ, Strieter RM, Coffey MJ, Markovitz DM: The C-X-C chemokine IP-10 stimulates HIV-1 replication. Virology. 2003, 307: 122-134. 10.1016/S0042-6822(02)00045-4.PubMedCrossRef
42.
Cinque P, Bestetti A, Marenzi R, Sala S, Gisslen M, Hagberg L, Price RW: Cerebrospinal fluid interferon-gamma-inducible protein 10 (IP-10, CXCL10) in HIV-1 infection. J Neuroimmunol. 2005, 168: 154-163. 10.1016/j.jneuroim.2005.07.002.PubMedCrossRef
43.
Ensoli B, Buonaguro L, Barillari G, Fiorelli V, Gendelman R, Morgan RA, Wingfield P, Gallo RC: Release, uptake, and effects of extracellular human immunodeficiency virus type 1 Tat protein on cell growth and viral transactivation. J Virol. 1993, 67: 277-287.PubMedPubMedCentral
44.
Chen P, Mayne M, Power C, Nath A: The Tat protein of HIV-1 induces tumor necrosis factor-alpha production. Implications for HIV-1-associated neurological diseases. J Biol Chem. 1997, 272: 22385-22388. 10.1074/jbc.272.36.22385.PubMedCrossRef
45.
Bennasser Y, Bahraoui E: HIV-1 Tat protein induces interleukin-10 in human peripheral blood monocytes: involvement of protein kinase C-betaII and -delta. FASEB J. 2002, 16: 546-554. 10.1096/fj.01-0775com.PubMedCrossRef
46.
Agostini C, Facco M, Siviero M, Carollo D, Galvan S, Cattelan AM, Zambello R, Trentin L, Semenzato G: CXC chemokines IP-10 and mig expression and direct migration of pulmonary CD8+/CXCR3+ T cells in the lungs of patients with HIV infection and T-cell alveolitis. Am J Respir Crit Care Med. 2000, 162: 1466-1473.PubMedCrossRef
47.
Enam S, Sweet TM, Amini S, Khalili K, Del Valle L: Evidence for involvement of transforming growth factor beta1 signaling pathway in activation of JC virus in human immunodeficiency virus 1-associated progressive multifocal leukoencephalopathy. Arch Pathol Lab Med. 2004, 128: 282-291.PubMed
48.
Zeng Y, Zhang X, Huang Z, Cheng L, Yao S, Qin D, Chen X, Tang Q, Lv Z, Zhang L: Intracellular Tat of human immunodeficiency virus type 1 activates lytic cycle replication of Kaposi's sarcoma-associated herpesvirus: role of JAK/STAT signaling. J Virol. 2007, 81: 2401-2417. 10.1128/JVI.02024-06.PubMedPubMedCentralCrossRef
49.
Tscherne DM, Jones CT, Evans MJ, Lindenbach BD, McKeating JA, Rice CM: Time- and temperature-dependent activation of hepatitis C virus for low-pH-triggered entry. J Virol. 2006, 80: 1734-1741. 10.1128/JVI.80.4.1734-1741.2006.PubMedPubMedCentralCrossRef
Metadata
Title
The Tat protein of human immunodeficiency virus-1 enhances hepatitis C virus replication through interferon gamma-inducible protein-10
Authors
Jing Qu
Qi Zhang
Youxing Li
Weiyong Liu
Lvxiao Chen
Ying Zhu
Jianguo Wu
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Immunology / Issue 1/2012
Electronic ISSN: 1471-2172
DOI
https://doi.org/10.1186/1471-2172-13-15

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Keynote webinar | Spotlight on medication adherence

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WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

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