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Cellular and molecular interactions in coinfection with hepatitis C virus and human immunodeficiency virus

Published online by Cambridge University Press:  20 October 2008

Barbara Roe
Affiliation:
Centre for Research in Infectious Diseases (CRID), School of Medicine & Medical Science, University College Dublin, Belfield, Dublin 4, Ireland.
William W. Hall*
Affiliation:
Centre for Research in Infectious Diseases (CRID), School of Medicine & Medical Science, University College Dublin, Belfield, Dublin 4, Ireland.
*
*Corresponding Author: William W. Hall, Centre for Research in Infectious Diseases, University College Dublin, Belfield, Dublin 4, Ireland; Tel: +353 1 7161236; Fax: +353  1 7161239; E-mail: [email protected]

Abstract

Coinfection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) is associated with increased HCV replication and a more rapid progression to severe liver disease, including the development of cirrhosis and hepatocellular carcinoma. In this review, we discuss the current understanding of the pathogenesis of HCV/HIV coinfection and the cellular and molecular mechanisms associated with the accelerated course of liver disease. The strength and breadth of HCV-specific T-cell responses are reduced in HCV/HIV-coinfected patients compared with those infected with HCV alone, suggesting that the immunosuppression induced by HIV compromises immune responses to HCV. HCV is not directly cytopathic, but many of the pathological changes observed in the liver of infected patients are a direct result of the intrahepatic antiviral immune responses. Apoptosis also has a role in HCV-mediated liver damage through the induction of apoptotic pathways involving the host immune response and HCV viral proteins. This review summarises the evidence correlating the role of cell-mediated immune responses and apoptosis with liver disease progression in HCV/HIV-coinfected patients.

Type
Review Article
Copyright
Copyright © Cambridge University Press 2008

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References

References

1Pawlotsky, J.M. (2004) Pathophysiology of hepatitis C virus infection and related liver disease. Trends Microbiol 12, 96-102CrossRefGoogle ScholarPubMed
2Perz, J. et al. (2004). Estimated Global Prevalence of Hepatitis C Virus Infection. 42nd Annual Meeting of the Infectious Diseases Society of America, Boston, MA, USA. Sept 30-Oct 3, 2004. Poster 957Google Scholar
3Palitzsch, K.D. et al. (1999) Prevalence of antibodies against hepatitis C virus in the adult German population. Eur J Gastroenterol Hepatol 11, 1215-1220CrossRefGoogle ScholarPubMed
4Mutimer, D.J. et al. (1995) Hepatitis C virus infection in the asymptomatic British blood donor. J Viral Hepat 2, 47-53CrossRefGoogle ScholarPubMed
5Meffre, C. et al. (2006) Prevalence of hepatitis B and hepatitis C in France, 2004. Journal of Clinical Virology 36 (Suppl 2), S197CrossRefGoogle Scholar
6Armstrong, G.L. et al. (2006) The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med 144, 705-714CrossRefGoogle ScholarPubMed
7Higuchi, M., Tanaka, E. and Kiyosawa, K. (2002) Epidemiology and clinical aspects on hepatitis C. Jpn J Infect Dis 55, 69-77Google ScholarPubMed
8Lei, X., Shigeko, N. and Deng, X. (1999) Prevalence of Hepatitis C Virus Infection in the General Population and Patients with Liver Disease in China. Hepatology Research 14, 135-143Google Scholar
9Xia, G. et al. (1996) Prevalence of Hepatitis B and C Virus Infections in the General Chinese Population. Results from a Nationwide Cross-sectional Seroepidemiologic Study of Hepatitis A, B, C, D, and E Virus Infections in China, 1992. International Hepatology Communications 5, 62-73CrossRefGoogle Scholar
10Frank, C. et al. (2000) The role of parenteral antischistosomal therapy in the spread of hepatitis C virus in Egypt. Lancet 355, 887-891CrossRefGoogle ScholarPubMed
11Schmeding, M. et al. (2007) Hepatitis C recurrence and fibrosis progression are not increased after living donor liver transplantation: a single-center study of 289 patients. Liver Transpl 13, 687-692CrossRefGoogle Scholar
12Denis, F. et al. (1997). [Seroprevalence of HBV, HCV and HDV hepatitis markers in 500 patients infected with the human immunodeficiency virus]. Pathol Biol (Paris) 45, 701-708Google ScholarPubMed
13Jones, R., Dunning, J. and Nelson, M. (2005) HIV and hepatitis C coinfection. Int J Clin Pract 59, 1082-1087CrossRefGoogle Scholar
14Sulkowski, M.S. and Thomas, D.L. (2003) Hepatitis C in the HIV-Infected Person. Ann Intern Med 138, 197-207CrossRefGoogle ScholarPubMed
15Seeff, L.B. (2002) Natural history of chronic hepatitis C. Hepatology 36 (Suppl 1), S35-46Google ScholarPubMed
16Garcia-Samaniego, J. et al. (2001) Hepatocellular carcinoma in HIV-infected patients with chronic hepatitis C. Am J Gastroenterol 96, 179-183CrossRefGoogle ScholarPubMed
17Soto, B. et al. (1997) Human immunodeficiency virus infection modifies the natural history of chronic parenterally-acquired hepatitis C with an unusually rapid progression to cirrhosis. J Hepatol 26, 1-5CrossRefGoogle ScholarPubMed
18Palella, F.J. Jr. et al. (1998) Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med 338, 853-860CrossRefGoogle ScholarPubMed
19Weber, R. et al. (2006) Liver-related deaths in persons infected with the human immunodeficiency virus: the D:A:D study. Arch Intern Med 166, 1632-1641Google Scholar
20Robertson, B. et al. (1998) Classification, nomenclature, and database development for hepatitis C virus (HCV) and related viruses: proposals for standardization. International Committee on Virus Taxonomy. Arch Virol 143, 2493-2503CrossRefGoogle ScholarPubMed
21Kaito, M. et al. (1994) Hepatitis C virus particle detected by immunoelectron microscopic study. J Gen Virol 75, 1755-1760CrossRefGoogle ScholarPubMed
22Rice, C. (1996). Flaviviridae: The viruses and their replication. In Fields Virology, 3rd ed.Lippencott-Raven, PhiladelphiaGoogle Scholar
23Tsukiyama-Kohara, K. et al. (1992) Internal ribosome entry site within hepatitis C virus RNA. J Virol 66, 1476-1483CrossRefGoogle ScholarPubMed
24Grakoui, A. et al. (1993) Expression and identification of hepatitis C virus polyprotein cleavage products. J Virol 67, 1385-1395CrossRefGoogle ScholarPubMed
25Santolini, E., Migliaccio, G. and La Monica, N. (1994) Biosynthesis and biochemical properties of the hepatitis C virus core protein. J Virol 68, 3631-3641CrossRefGoogle ScholarPubMed
26Griffin, S.D. et al. (2003) The p7 protein of hepatitis C virus forms an ion channel that is blocked by the antiviral drug, Amantadine. FEBS Lett 535, 34-38CrossRefGoogle ScholarPubMed
27Pavlovic, D. et al. (2003) The hepatitis C virus p7 protein forms an ion channel that is inhibited by long-alkyl-chain iminosugar derivatives. Proc Natl Acad Sci U S A 100, 6104-6108CrossRefGoogle ScholarPubMed
28Steinmann, E. et al. (2007) Hepatitis C Virus p7 Protein Is Crucial for Assembly and Release of Infectious Virions. PLoS Pathog 3, e103CrossRefGoogle ScholarPubMed
29Grakoui, A. et al. (1993) A second hepatitis C virus-encoded proteinase. Proc Natl Acad Sci U S A 90, 10583-10587CrossRefGoogle ScholarPubMed
30Lindenbach, B.D. and Rice, C.M. (2005) Unravelling hepatitis C virus replication from genome to function. Nature 436, 933-938CrossRefGoogle Scholar
31Brass, V., Moradpour, D. and Blum, H.E. (2006) Molecular virology of hepatitis C virus (HCV, 2006 update. Int J Med Sci 3, 29-34CrossRefGoogle ScholarPubMed
32Elazar, M. et al. (2004) An N-terminal amphipathic helix in hepatitis C virus (HCV) NS4B mediates membrane association, correct localization of replication complex proteins, and HCV RNA replication. J Virol 78, 11393-11400CrossRefGoogle ScholarPubMed
33Egger, D. et al. (2002) Expression of hepatitis C virus proteins induces distinct membrane alterations including a candidate viral replication complex. J Virol 76, 5974-5984CrossRefGoogle ScholarPubMed
34Tan, S.L. and Katze, M.G. (2001) How hepatitis C virus counteracts the interferon response: the jury is still out on NS5A. Virology 284, 1-12CrossRefGoogle ScholarPubMed
35Behrens, S.E., Tomei, L. and De Francesco, R. (1996) Identification and properties of the RNA-dependent RNA polymerase of hepatitis C virus. Embo J 15, 12-22CrossRefGoogle ScholarPubMed
36Cleghorn, F.R. et al. (2005). Human Immunodeficiency Viruses. In Mandell, Douglas, and Bennett's principles and practice of infectious diseases, pp. 2119-2133. Elsevier, Churchill Livingstone, New York.Google Scholar
37Frankel, A.D. and Young, J.A. (1998) HIV-1: fifteen proteins and an RNA. Annu Rev Biochem 67, 1-25CrossRefGoogle Scholar
38Hearps, A.C. and Jans, D.A. (2007) Regulating the functions of the HIV-1 matrix protein. AIDS Res Hum Retroviruses 23, 341-346CrossRefGoogle ScholarPubMed
39Paxton, W., Connor, R.I. and Landau, N.R. (1993) Incorporation of Vpr into human immunodeficiency virus type 1 virions: requirement for the p6 region of gag and mutational analysis. J Virol 67, 7229-7237CrossRefGoogle ScholarPubMed
40Hill, M., Tachedjian, G. and Mak, J. (2005) The packaging and maturation of the HIV-1 Pol proteins. Curr HIV Res 3, 73-85CrossRefGoogle ScholarPubMed
41Arya, S.K. et al. (1985) Trans-activator gene of human T-lymphotropic virus type III (HTLV-III). Science 229, 69-73CrossRefGoogle ScholarPubMed
42Fisher, A.G. et al. (1986) The trans-activator gene of HTLV-III is essential for virus replication. Nature 320, 367-371CrossRefGoogle ScholarPubMed
43Felber, B.K. et al. (1989) rev protein of human immunodeficiency virus type 1 affects the stability and transport of the viral mRNA. Proc Natl Acad Sci U S A 86, 1495-1499CrossRefGoogle ScholarPubMed
44Garcia, J.V. and Miller, A.D. (1992) Downregulation of cell surface CD4 by nef. Res Virol 143, 52-55CrossRefGoogle ScholarPubMed
45Willey, R.L. et al. (1992) Human immunodeficiency virus type 1 Vpu protein regulates the formation of intracellular gp160-CD4 complexes. J Virol 66, 226-234CrossRefGoogle ScholarPubMed
46Heinzinger, N.K. et al. (1994) The Vpr protein of human immunodeficiency virus type 1 influences nuclear localization of viral nucleic acids in nondividing host cells. Proc Natl Acad Sci U S A 91, 7311-7315CrossRefGoogle ScholarPubMed
47Greub, G. et al. (2000) Clinical progression, survival, and immune recovery during antiretroviral therapy in patients with HIV-1 and hepatitis C virus coinfection: the Swiss HIV Cohort Study. Lancet 356, 1800-1805CrossRefGoogle ScholarPubMed
48De Luca, A. et al. (2002) Coinfection with hepatitis viruses and outcome of initial antiretroviral regimens in previously naive HIV-infected subjects. Arch Intern Med 162, 2125-2132CrossRefGoogle ScholarPubMed
49Piroth, L. et al. (2000) Hepatitis C virus coinfection is a negative prognostic factor for clinical evolution in human immunodeficiency virus-positive patients. J Viral Hepat 7, 302-308CrossRefGoogle ScholarPubMed
50Rockstroh, J.K. et al. (2005) Influence of hepatitis C virus infection on HIV-1 disease progression and response to highly active antiretroviral therapy. J Infect Dis 192, 992-1002CrossRefGoogle ScholarPubMed
51Sulkowski, M.S. et al. (2002) Hepatitis C and progression of HIV disease. J Am Med Ass 288, 199-206CrossRefGoogle ScholarPubMed
52Bonacini, M. et al. (2004) Survival in patients with HIV infection and viral hepatitis B or C: a cohort study. Aids 18, 2039-2045CrossRefGoogle ScholarPubMed
53Dorrucci, M. et al. (1995) Coinfection of hepatitis C virus with human immunodeficiency virus and progression to AIDS. Italian Seroconversion Study. J Infect Dis 172, 1503-1508CrossRefGoogle ScholarPubMed
54Lincoln, D., Petoumenos, K. and Dore, G.J. (2003) HIV/HBV and HIV/HCV coinfection, and outcomes following highly active antiretroviral therapy. HIV Med 4, 241-249CrossRefGoogle ScholarPubMed
55Staples, C.T. Jr, Rimland, D. and Dudas, D. (1999) Hepatitis C in the HIV (human immunodeficiency virus) Atlanta V.A. (Veterans Affairs Medical Center) Cohort Study (HAVACS, the effect of coinfection on survival. Clin Infect Dis 29, 150-154CrossRefGoogle Scholar
56Melvin, D.C. et al. (2000) The impact of coinfection with hepatitis C virus and HIV on the tolerability of antiretroviral therapy. Aids 14, 463-465CrossRefGoogle ScholarPubMed
57Sulkowski, M.S. et al. (2002) Hepatotoxicity associated with nevirapine or efavirenz-containing antiretroviral therapy: role of hepatitis C and B infections. Hepatology 35, 182-189CrossRefGoogle ScholarPubMed
58Bonacini, M. et al. (1999) Patients coinfected with human immunodeficiency virus and hepatitis C virus demonstrate higher levels of hepatic HCV RNA. J Viral Hepat 6, 203-208CrossRefGoogle ScholarPubMed
59Sherman, K.E. et al. (1993) Quantitative evaluation of hepatitis C virus RNA in patients with concurrent human immunodeficiency virus infections. J Clin Microbiol 31, 2679-2682CrossRefGoogle ScholarPubMed
60Daar, E.S. et al. (2001) Relation between HIV-1 and hepatitis C viral load in patients with hemophilia. J Acquir Immune Defic Syndr 26, 466-472CrossRefGoogle ScholarPubMed
61Eyster, M.E. et al. (1994) Increasing hepatitis C virus RNA levels in hemophiliacs: relationship to human immunodeficiency virus infection and liver disease. Multicenter Hemophilia Cohort Study. Blood 84, 1020-1023CrossRefGoogle ScholarPubMed
62Hadziyannis, S.J. et al. (2004) Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med 140, 346-355CrossRefGoogle ScholarPubMed
63Manns, M.P. et al. (2001) Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 358, 958-965CrossRefGoogle ScholarPubMed
64Carrat, F. et al. (2004) Pegylated interferon alfa-2b vs standard interferon alfa-2b, plus ribavirin, for chronic hepatitis C in HIV-infected patients: a randomized controlled trial. J Am Med Ass 292, 2839-2848CrossRefGoogle ScholarPubMed
65Chung, R.T. et al. (2004) Peginterferon Alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV-coinfected persons. N Engl J Med 351, 451-459CrossRefGoogle ScholarPubMed
66Torriani, F.J. et al. (2004) Peginterferon Alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N Engl J Med 351, 438-450CrossRefGoogle ScholarPubMed
67Nunez, M. et al. (2007) Role of weight-based ribavirin dosing and extended duration of therapy in chronic hepatitis C in HIV-infected patients: the PRESCO trial. AIDS Res Hum Retroviruses 23, 972-982CrossRefGoogle Scholar
68Benhamou, Y. et al. (1999) Liver fibrosis progression in human immunodeficiency virus and hepatitis C virus coinfected patients. The Multivirc Group. Hepatology 30, 1054-1058CrossRefGoogle Scholar
69Canchis, P.W. et al. (2004) Intrahepatic CD4+ cell depletion in hepatitis C virus/HIV-coinfected patients. J Acquir Immune Defic Syndr 37, 1125-1131CrossRefGoogle ScholarPubMed
70Brau, N. et al. (2006) Slower fibrosis progression in HIV/HCV-coinfected patients with successful HIV suppression using antiretroviral therapy. J Hepatol 44, 47-55CrossRefGoogle ScholarPubMed
71Qurishi, N. et al. (2003) Effect of antiretroviral therapy on liver-related mortality in patients with HIV and hepatitis C virus coinfection. Lancet 362, 1708-1713CrossRefGoogle Scholar
72Diepolder, H.M. et al. (1995) Possible mechanism involving T-lymphocyte response to non-structural protein 3 in viral clearance in acute hepatitis C virus infection. Lancet 346, 1006-1007CrossRefGoogle ScholarPubMed
73Lechner, F. et al. (2000) Analysis of successful immune responses in persons infected with hepatitis C virus. J Exp Med 191, 1499-1512CrossRefGoogle ScholarPubMed
74Wedemeyer, H. et al. (2002) Impaired effector function of hepatitis C virus-specific CD8+ T cells in chronic hepatitis C virus infection. J Immunol 169, 3447-3458CrossRefGoogle ScholarPubMed
75Grakoui, A. et al. (2003) HCV persistence and immune evasion in the absence of memory T cell help. Science 302, 659-662CrossRefGoogle ScholarPubMed
76Shoukry, N.H. et al. (2003) Memory CD8+ T cells are required for protection from persistent hepatitis C virus infection. J Exp Med 197, 1645-1655CrossRefGoogle ScholarPubMed
77Shedlock, D.J. and Shen, H. (2003) Requirement for CD4 T cell help in generating functional CD8 T cell memory. Science 300, 337-339CrossRefGoogle ScholarPubMed
78Gerlach, J.T. et al. (1999) Recurrence of hepatitis C virus after loss of virus-specific CD4(+) T-cell response in acute hepatitis C. Gastroenterology 117, 933-941CrossRefGoogle ScholarPubMed
79Tsai, S.L. et al. (1997) Detection of type 2-like T-helper cells in hepatitis C virus infection: implications for hepatitis C virus chronicity. Hepatology 25, 449-458CrossRefGoogle ScholarPubMed
80Bjoro, K. et al. (1994) Hepatitis C infection in patients with primary hypogammaglobulinemia after treatment with contaminated immune globulin. N Engl J Med 331, 1607-1611CrossRefGoogle ScholarPubMed
81Chang, K.M. et al. (1997) Immunological significance of cytotoxic T lymphocyte epitope variants in patients chronically infected by the hepatitis C virus. J Clin Invest 100, 2376-2385CrossRefGoogle ScholarPubMed
82Frasca, L. et al. (1999) Hypervariable region 1 variants act as TCR antagonists for hepatitis C virus-specific CD4+ T cells. J Immunol 163, 650-658CrossRefGoogle ScholarPubMed
83Erickson, A.L. et al. (2001) The outcome of hepatitis C virus infection is predicted by escape mutations in epitopes targeted by cytotoxic T lymphocytes. Immunity 15, 883-895CrossRefGoogle ScholarPubMed
84Timm, J. et al. (2004) CD8 epitope escape and reversion in acute HCV infection. J Exp Med 200(12), 1593-604CrossRefGoogle ScholarPubMed
85Weiner, A. et al. (1995) Persistent hepatitis C virus infection in a chimpanzee is associated with emergence of a cytotoxic T lymphocyte escape variant. Proc Natl Acad Sci U S A 92, 2755-2759CrossRefGoogle Scholar
86Thimme, R. et al. (2001) Determinants of viral clearance and persistence during acute hepatitis C virus infection. J Exp Med 194, 1395-1406CrossRefGoogle ScholarPubMed
87Bain, C. et al. (2001) Impaired allostimulatory function of dendritic cells in chronic hepatitis C infection. Gastroenterology 120, 512-524CrossRefGoogle ScholarPubMed
88Brady, M.T. et al. (2003) Hepatitis C virus non-structural protein 4 suppresses Th1 responses by stimulating IL-10 production from monocytes. Eur J Immunol 33, 3448-3457CrossRefGoogle ScholarPubMed
89Dolganiuc, A. et al. (2003) Hepatitis C virus core and nonstructural protein 3 proteins induce pro- and anti-inflammatory cytokines and inhibit dendritic cell differentiation. J Immunol 170, 5615-5624CrossRefGoogle ScholarPubMed
90Disson, O. et al. (2004) Impaired clearance of virus-infected hepatocytes in transgenic mice expressing the hepatitis C virus polyprotein. Gastroenterology 126, 859-872CrossRefGoogle ScholarPubMed
91Frelin, L. et al. (2006) The hepatitis C virus and immune evasion: non-structural 3/4A transgenic mice are resistant to lethal tumour necrosis factor {alpha} mediated liver disease. Gut 55, 1475-1483CrossRefGoogle ScholarPubMed
92Capa, L. et al. (2007) Influence of HCV genotype and coinfection with human immunodeficiency virus on CD4(+) and CD8(+) T-cell responses to hepatitis C virus. J Med Virol 79, 503-510CrossRefGoogle ScholarPubMed
93Dutoit, V. et al. (2005) Differences in HCV-specific T cell responses between chronic HCV infection and HIV/HCV coinfection. Eur J Immunol 35, 3493-3504CrossRefGoogle Scholar
94Graham, C.S. et al. (2004) Comparison of HCV-specific intrahepatic CD4+ T cells in HIV/HCV versus HCV. Hepatology 40, 125-132CrossRefGoogle ScholarPubMed
95Valdez, H. et al. (2000) Immune responses to hepatitis C and non-hepatitis C antigens in hepatitis C virus infected and HIV-1 coinfected patients. Aids 14, 2239-2246CrossRefGoogle ScholarPubMed
96Graham, C.S. et al. (2005) Antigen-specific immune responses and liver histology in HIV and hepatitis C coinfection. Aids 19, 767-773CrossRefGoogle ScholarPubMed
97Brainard, D.M. et al. (2007) Decreased CXCR3+ CD8 T cells in advanced human immunodeficiency virus infection suggest that a homing defect contributes to cytotoxic T-lymphocyte dysfunction. J Virol 81, 8439-8450CrossRefGoogle ScholarPubMed
98Lohr, H.F. et al. (1998) The cellular immune responses induced in the follow-up of interferon-alpha treated patients with chronic hepatitis C may determine the therapy outcome. J Hepatol 29, 524-532CrossRefGoogle ScholarPubMed
99Thomas, D.L. (2006) Options for treatment of hepatitis C in HIV-infected persons. J Hepatol 44 (Suppl.) S40-43CrossRefGoogle ScholarPubMed
100Koziel, M.J. et al. (1992) Intrahepatic cytotoxic T lymphocytes specific for hepatitis C virus in persons with chronic hepatitis. J Immunol 149, 3339-3344CrossRefGoogle ScholarPubMed
101Tseng, C.T. et al. (2001) Characterization of liver T-cell receptor gammadelta T cells obtained from individuals chronically infected with hepatitis C virus (HCV, evidence for these T cells playing a role in the liver pathology associated with HCV infections. Hepatology 33, 1312-1320CrossRefGoogle ScholarPubMed
102Jacobson Brown, P.M. and Neuman, M.G. (2001) Immunopathogenesis of hepatitis C viral infection: Th1/Th2 responses and the role of cytokines. Clin Biochem 34, 167-171CrossRefGoogle ScholarPubMed
103Alkhatib, G. et al. (1996) CC CKR5: a RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for macrophage-tropic HIV-1. Science 272, 1955-1958CrossRefGoogle ScholarPubMed
104Feng, Y. et al. (1996) HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 272, 872-877CrossRefGoogle ScholarPubMed
105Kim, C.H. et al. (2001) Rules of chemokine receptor association with T cell polarization in vivo. J Clin Invest 108, 1331-1339CrossRefGoogle Scholar
106Sallusto, F. et al. (1998) Flexible programs of chemokine receptor expression on human polarized T helper 1 and 2 lymphocytes. J Exp Med 187, 875-883CrossRefGoogle ScholarPubMed
107Apolinario, A. et al. (2002) Increased expression of T cell chemokines and their receptors in chronic hepatitis C: relationship with the histological activity of liver disease. Am J Gastroenterol 97, 2861-2870CrossRefGoogle ScholarPubMed
108Shields, P.L. et al. (1999) Chemokine and chemokine receptor interactions provide a mechanism for selective T cell recruitment to specific liver compartments within hepatitis C-infected liver. J Immunol 163, 6236-6243CrossRefGoogle ScholarPubMed
109Taub, D.D. et al. (1993) 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 177, 1809-1814CrossRefGoogle Scholar
110Butera, D. et al. (2005) Plasma chemokine levels correlate with the outcome of antiviral therapy in patients with hepatitis C. Blood 106, 1175-1182CrossRefGoogle ScholarPubMed
111Mihm, S., Schweyer, S. and Ramadori, G. (2003) 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 70, 562-570CrossRefGoogle ScholarPubMed
112Harvey, C.E. et al. (2003) 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 74, 360-369CrossRefGoogle ScholarPubMed
113Romero, A.I. et al. (2006) 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 194, 895-903CrossRefGoogle ScholarPubMed
114Diago, M. et al. (2006) Association of pretreatment serum interferon gamma inducible protein 10 levels with sustained virological response to peginterferon plus ribavirin therapy in genotype 1 infected patients with chronic hepatitis C. Gut 55, 374-379CrossRefGoogle ScholarPubMed
115Cinque, P. et al. (2005) Cerebrospinal fluid interferon-gamma-inducible protein 10 (IP-10, CXCL10) in HIV-1 infection. J Neuroimmunol 168, 154-163CrossRefGoogle ScholarPubMed
116Stylianou, E. et al. (2000) 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 119, 479-485CrossRefGoogle ScholarPubMed
117Lane, B.R. et al. (2003) The C-X-C chemokine IP-10 stimulates HIV-1 replication. Virology 307, 122-134CrossRefGoogle ScholarPubMed
118Roe, B. et al. (2007) Elevated Serum Levels of Interferon-gamma-Inducible Protein-10 in Patients Coinfected with Hepatitis C Virus and HIV. J Infect Dis 196, 1053-1057CrossRefGoogle ScholarPubMed
119Balasubramanian, A., Ganju, R.K. and Groopman, J.E. (2003) Hepatitis C virus and HIV envelope proteins collaboratively mediate interleukin-8 secretion through activation of p38 MAP kinase and SHP2 in hepatocytes. J Biol Chem 278, 35755-35766CrossRefGoogle ScholarPubMed
120Kuntzen, T. et al. (2008) Intrahepatic mRNA expression in hepatitis C virus and HIV/hepatitis C virus coinfection: infiltrating cells, cytokines, and influence of HAART. Aids 22, 203-210CrossRefGoogle ScholarPubMed
121Farinati, F. et al. (2006) Oxidative damage, pro-inflammatory cytokines, TGF-alpha and c-myc in chronic HCV-related hepatitis and cirrhosis. World J Gastroenterol 12, 2065-2069CrossRefGoogle Scholar
122Zekri, A.R. et al. (2005) Cytokine profile in Egyptian hepatitis C virus genotype-4 in relation to liver disease progression. World J Gastroenterol 11, 6624-6630CrossRefGoogle ScholarPubMed
123Breen, E.C. et al. (1990) Infection with HIV is associated with elevated IL-6 levels and production. J Immunol 144, 480-484CrossRefGoogle ScholarPubMed
124Molina, J.M. et al. (1989) Production of tumor necrosis factor alpha and interleukin 1 beta by monocytic cells infected with human immunodeficiency virus. J Clin Invest 84, 733-737CrossRefGoogle ScholarPubMed
125Folks, T.M. et al. (1989) Tumor necrosis factor alpha induces expression of human immunodeficiency virus in a chronically infected T-cell clone. Proc Natl Acad Sci U S A 86, 2365-2368CrossRefGoogle Scholar
126Poli, G. et al. (1990) Interleukin 6 induces human immunodeficiency virus expression in infected monocytic cells alone and in synergy with tumor necrosis factor alpha by transcriptional and post-transcriptional mechanisms. J Exp Med 172, 151-158CrossRefGoogle ScholarPubMed
127Poli, G., Kinter, A.L. and Fauci, A.S. (1994) Interleukin 1 induces expression of the human immunodeficiency virus alone and in synergy with interleukin 6 in chronically infected U1 cells: inhibition of inductive effects by the interleukin 1 receptor antagonist. Proc Natl Acad Sci U S A 91, 108-112CrossRefGoogle ScholarPubMed
128Abbate, I. et al. (2004) Intra-hepatic messenger RNA levels for interferons and related genes in hepatitis C virus/HIV coinfected patients. Aids 18, 691-692CrossRefGoogle Scholar
129Blackard, J.T. et al. (2006) Intrahepatic cytokine expression is downregulated during HCV/HIV coinfection. J Med Virol 78, 202-207CrossRefGoogle Scholar
130Gonzalez, S.A. et al. (2007) Hepatic inflammatory cytokine mRNA expression in hepatitis C virus-human immunodeficiency virus coinfection. J Viral Hepat 15, 331-338CrossRefGoogle Scholar
131Sitia, G. et al. (2006) Naive HIV/HCV-coinfected patients have higher intrahepatic pro-inflammatory cytokines than coinfected patients treated with antiretroviral therapy. Antivir Ther 11, 385-389CrossRefGoogle ScholarPubMed
132Guicciardi, M.E. and Gores, G.J. (2005) Apoptosis: a mechanism of acute and chronic liver injury. Gut 54, 1024-1033CrossRefGoogle ScholarPubMed
133Jin, Z. and El-Deiry, W.S. (2005) Overview of cell death signaling pathways. Cancer Biol Ther 4, 139-163CrossRefGoogle ScholarPubMed
134Rupinder, S.K., Gurpreet, A.K. and Manjeet, S. (2007) Cell suicide and caspases. Vascul Pharmacol 46, 383-393CrossRefGoogle ScholarPubMed
135Riedl, S.J. and Salvesen, G.S. (2007) The apoptosome: signalling platform of cell death. Nat Rev Mol Cell Biol 8, 405-413CrossRefGoogle ScholarPubMed
136Bantel, H. et al. (2001) Caspase activation correlates with the degree of inflammatory liver injury in chronic hepatitis C virus infection. Hepatology 34, 758-767CrossRefGoogle ScholarPubMed
137Bantel, H. et al. (2001) Detection of elevated caspase activation and early apoptosis in liver diseases. Eur J Cell Biol 80, 230-239CrossRefGoogle ScholarPubMed
138Calabrese, F. et al. (2000) Liver cell apoptosis in chronic hepatitis C correlates with histological but not biochemical activity or serum HCV-RNA levels. Hepatology 31, 1153-1159CrossRefGoogle ScholarPubMed
139Woo, M. et al. (1999) In vivo evidence that caspase-3 is required for Fas-mediated apoptosis of hepatocytes. J Immunol 163, 4909-4916CrossRefGoogle ScholarPubMed
140Kunstle, G. et al. (1997) ICE-protease inhibitors block murine liver injury and apoptosis caused by CD95 or by TNF-alpha. Immunol Lett 55, 5-10CrossRefGoogle ScholarPubMed
141Rouquet, N. et al. (1996) ICE inhibitor YVADcmk is a potent therapeutic agent against in vivo liver apoptosis. Curr Biol 6, 1192-1195CrossRefGoogle ScholarPubMed
142Chou, A.H. et al. (2005) Hepatitis C virus core protein modulates TRAIL-mediated apoptosis by enhancing Bid cleavage and activation of mitochondria apoptosis signaling pathway. J Immunol 174, 2160-2166CrossRefGoogle ScholarPubMed
143Okuda, M. et al. (2002) Mitochondrial injury, oxidative stress, and antioxidant gene expression are induced by hepatitis C virus core protein. Gastroenterology 122, 366-375CrossRefGoogle ScholarPubMed
144Otsuka, M. et al. (2002) Hepatitis C virus core protein inhibits apoptosis via enhanced Bcl-xL expression. Virology 296, 84-93CrossRefGoogle ScholarPubMed
145Ray, R.B. et al. (1998) Inhibition of tumor necrosis factor (TNF-alpha)-mediated apoptosis by hepatitis C virus core protein. J Biol Chem 273, 2256-2259CrossRefGoogle ScholarPubMed
146Prikhod'ko, E.A. et al. (2004) The NS3 protein of hepatitis C virus induces caspase-8-mediated apoptosis independent of its protease or helicase activities. Virology 329, 53-67CrossRefGoogle ScholarPubMed
147Meylan, E. et al. (2005) Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature 437, 1167-1172CrossRefGoogle ScholarPubMed
148Chung, Y.L., Sheu, M.L. and Yen, S.H. (2003) Hepatitis C virus NS5A as a potential viral Bcl-2 homologue interacts with Bax and inhibits apoptosis in hepatocellular carcinoma. Int J Cancer 107, 65-73CrossRefGoogle ScholarPubMed
149Wang, J. et al. (2006) Hepatitis C virus non-structural protein NS5A interacts with FKBP38 and inhibits apoptosis in Huh7 hepatoma cells. FEBS Lett 580, 4392-4400CrossRefGoogle ScholarPubMed
150Lan, K.H. et al. (2002) HCV NS5A interacts with p53 and inhibits p53-mediated apoptosis. Oncogene 21, 4801-4811CrossRefGoogle ScholarPubMed
151Gong, G. et al. (2001) Human hepatitis C virus NS5A protein alters intracellular calcium levels, induces oxidative stress, and activates STAT-3 and NF-kappa B. Proc Natl Acad Sci U S A 98, 9599-9604CrossRefGoogle ScholarPubMed
152Street, A. et al. (2004) The Hepatitis C virus NS5A protein activates a phosphoinositide 3-kinase-dependent survival signaling cascade. J Biol Chem 279, 12232-12241CrossRefGoogle ScholarPubMed
153Siavoshian, S. et al. (2005) Hepatitis C virus core, NS 3, NS5A, NS5B proteins induce apoptosis in mature dendritic cells. J Med Virol 75, 402-411CrossRefGoogle Scholar
154Munshi, N. et al. (2003) Hepatitis C and human immunodeficiency virus envelope proteins cooperatively induce hepatocytic apoptosis via an innocent bystander mechanism. J Infect Dis 188, 1192-1204CrossRefGoogle ScholarPubMed
155Balasubramanian, A. et al. (2005) Molecular mechanism of hepatic injury in coinfection with hepatitis C virus and HIV. Clin Infect Dis 41 (Suppl. 1), S32-37CrossRefGoogle ScholarPubMed
156Balasubramanian, A., Ganju, R.K. and Groopman, J.E. (2006) Signal transducer and activator of transcription factor 1 mediates apoptosis induced by hepatitis C virus and HIV envelope proteins in hepatocytes. J Infect Dis 194, 670-681CrossRefGoogle ScholarPubMed
157Macias, J. et al. (2005) Increased hepatocyte fas expression and apoptosis in HIV and hepatitis C virus coinfection. J Infect Dis 192, 1566-1576CrossRefGoogle ScholarPubMed
158Autran, B. et al. (1997) Positive effects of combined antiretroviral therapy on CD4+ T cell homeostasis and function in advanced HIV disease. Science 277, 112-116CrossRefGoogle Scholar
159Pontesilli, O. et al. (1999) Antigen-specific T-lymphocyte proliferative responses during highly active antiretroviral therapy (HAART) of HIV-1 infection. Immunol Lett 66, 213-217CrossRefGoogle ScholarPubMed
160Tilton, J.C. et al. (2007) Changes in paracrine interleukin-2 requirement, CCR7 expression, frequency, and cytokine secretion of human immunodeficiency virus-specific CD4+ T cells are a consequence of antigen load. J Virol 81, 2713-2725CrossRefGoogle ScholarPubMed
161Pockros, P.J. et al. (2007) Oral IDN-6556, an antiapoptotic caspase inhibitor, may lower aminotransferase activity in patients with chronic hepatitis C. Hepatology 46, 324-329CrossRefGoogle ScholarPubMed

Further reading, resources and contacts

Malhi, H. and Gores, G.J. (2008) Cellular and Molecular Mechanisms of Liver Injury. Gastroenterology 134, 1641-1654CrossRefGoogle ScholarPubMed
Klenerman, P. and Kim, A. (2007) HCV-HIV Coinfection: Simple Messages from a Complex Disease. PLoS Med 4, 1608-1614CrossRefGoogle ScholarPubMed
The latest reports and articles on HCV/HIV coinfection, including treatment updates and recent HCV and HIV related conferences, can be found at: http://www.hivandhepatitis.com/hiv_hcv_co_inf_articles.htmlGoogle Scholar
Up-to-date research and treatment news on HCV infection, diagnosis, treatments and liver disease is available at: http://www.hepatitis-central.com/Google Scholar
Malhi, H. and Gores, G.J. (2008) Cellular and Molecular Mechanisms of Liver Injury. Gastroenterology 134, 1641-1654CrossRefGoogle ScholarPubMed
Klenerman, P. and Kim, A. (2007) HCV-HIV Coinfection: Simple Messages from a Complex Disease. PLoS Med 4, 1608-1614CrossRefGoogle ScholarPubMed
The latest reports and articles on HCV/HIV coinfection, including treatment updates and recent HCV and HIV related conferences, can be found at: http://www.hivandhepatitis.com/hiv_hcv_co_inf_articles.htmlGoogle Scholar
Up-to-date research and treatment news on HCV infection, diagnosis, treatments and liver disease is available at: http://www.hepatitis-central.com/Google Scholar