Since the identification of HIV and HCV much progress has been made in the understanding of their life cycle and interaction with the host immune system. Despite these viruses markedly differ in their virological properties and in their pathogenesis, they share many common features in their immune escape and survival strategy. Both viruses have developed sophisticated ways to subvert and antagonize host innate and adaptive immune responses. In the last years, much effort has been done in the study of the AIDS pathogenesis and in the development of efficient treatment strategies, and a fatal infection has been transformed in a potentially chronic pathology. Much of this knowledge is now being transferred in the HCV research field, especially in the development of new drugs, although a big difference still remains between the outcome of the two infections, being HCV eradicable after treatment, whereas HIV eradication remains at present unachievable due to the establishment of reservoirs. In this review, we present current knowledge on innate and adaptive immune recognition and activation during HIV and HCV mono-infections and evasion strategies. We also discuss the genetic associations between components of the immune system, the course of infection, and the outcome of the therapies. 1. Introduction 1.1. Human Immunodeficiency Virus Infection Human immunodeficiency virus (HIV) is a retrovirus of the Lentiviridae family. This positive strand RNA virus infects specific cell populations of the immune system through its receptor specificity. At present, more than 33 million people are infected with HIV. HIV infection is characterized by an acute and a chronic phase, possibly leading to AIDS. Immediately after infection the viral load increases with exponential growth kinetics and CD4+ T cells rapidly decline [1, 2]. The peak of this growth curve coincides with the onset of a strong host immune response resulting in decreasing viral load and increasing number of circulating virus-specific CD4+ T cells. Then, the acute phase of HIV infection is accompanied by a selective and dramatic depletion of CD4+CCR5+ memory T cells predominantly from mucosal surfaces. This loss is largely irreversible and ultimately leads to the failure of the host immune defenses to clear the infection [3, 4]. This allows HIV to establish life-long latency and chronic infection. Over the chronic phase of infection, the viral load remains stable, whereas CD4+ T cell levels gradually decline [5]. The chronic phase is clinically latent, but eventually without therapeutic intervention, the
References
[1]
A. J. McMichael, P. Borrow, G. D. Tomaras, N. Goonetilleke, and B. F. Haynes, “The immune response during acute HIV-1 infection: clues for vaccine development,” Nature Reviews Immunology, vol. 10, no. 1, pp. 11–23, 2010.
[2]
M. Cadogan and A. G. Dalgleish, “HIV immunopathogenesis and strategies for intervention,” Lancet Infectious Diseases, vol. 8, no. 11, pp. 675–684, 2008.
[3]
D. Warrilow, D. Stenzel, and D. Harrich, “Isolated HIV-1 core is active for reverse transcription,” Retrovirology, vol. 4, article 77, 2007.
[4]
Z. Grossman, M. Meier-Schellersheim, W. E. Paul, and L. J. Picker, “Pathogenesis of HIV infection: what the virus spares is as important as what it destroys,” Nature Medicine, vol. 12, no. 3, pp. 289–295, 2006.
[5]
T. W. Schacker, J. P. Hughes, T. Shea, R. W. Coombs, and L. Corey, “Biological and virologic characteristics of primary HIV infection,” Annals of Internal Medicine, vol. 128, no. 8, pp. 613–620, 1998.
[6]
E. S. Ford, C. E. Puronen, and I. Sereti, “Immunopathogenesis of asymptomatic chronic HIV Infection: the calm before the storm,” Current Opinion in HIV and AIDS, vol. 4, no. 3, pp. 206–214, 2009.
[7]
S. G. Deeks and B. D. Walker, “The immune response to AIDS virus infection: good, bad, or both?” Journal of Clinical Investigation, vol. 113, no. 6, pp. 808–810, 2004.
[8]
T. H. Mogensen, J. Melchjorsen, C. S. Larsen, and S. R. Paludan, “Innate immune recognition and activation during HIV infection,” Retrovirology, vol. 7, article 54, 2010.
[9]
B. Rehermann, “Hepatitis C virus versus innate and adaptive immune responses: a tale of coevolution and coexistence,” Journal of Clinical Investigation, vol. 119, no. 7, pp. 1745–1754, 2009.
[10]
M. Wawrzynowicz-Syczewska, J. Kubicka, Z. Lewandowski, A. Boroń-Kaczmarska, and M. Radkowski, “Natural history of acute symptomatic hepatitis type C,” Infection, vol. 32, no. 3, pp. 138–143, 2004.
[11]
J. T. Gerlach, H. M. Diepolder, R. Zachoval et al., “Acute hepatitis C: high rate of both spontaneous and treatment-induced viral clearance,” Gastroenterology, vol. 125, no. 1, pp. 80–88, 2003.
[12]
J. M. Micallef, J. M. Kaldor, and G. J. Dore, “Spontaneous viral clearance following acute hepatitis C infection: a systematic review of longitudinal studies,” Journal of Viral Hepatitis, vol. 13, no. 1, pp. 34–41, 2006.
[13]
C. B. Bigger, K. M. Brasky, and R. E. Lanford, “DNA microarray analysis of chimpanzee liver during acute resolving hepatitis C virus infection,” Journal of Virology, vol. 75, no. 15, pp. 7059–7066, 2001.
[14]
A. I. Su, J. P. Pezacki, L. Wodicka et al., “Genomic analysis of the host response to hepatitis C virus infection,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 24, pp. 15669–15674, 2002.
[15]
T. Wakita, T. Pietschmann, T. Kato et al., “Production of infectious hepatitis C virus in tissue culture from a cloned viral genome,” Nature Medicine, vol. 11, no. 7, pp. 791–796, 2005.
[16]
J. Zhong, P. Gastaminza, G. Cheng et al., “Robust hepatitis C virus infection in vitro,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 26, pp. 9294–9299, 2005.
[17]
M. Yi, R. A. Villanueva, D. L. Thomas, T. Wakita, and S. M. Lemon, “Production of infectious genotype 1a hepatitis C virus (Hutchinson strain) in cultured human hepatoma cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 7, pp. 2310–2315, 2006.
[18]
G. Duverlie and C. Wychowski, “Cell culture systems for the hepatitis C virus,” World Journal of Gastroenterology, vol. 13, no. 17, pp. 2442–2445, 2007.
[19]
M. S. Sulkowski, “Hepatitis C virus-human immunodeficiency virus coinfection,” Liver International, vol. 32, supplement 1, pp. 129–134, 2012.
[20]
M. Jones and Y. Nú？ez, “HIV and hepatitis C co-infection: the role of HAART in HIV/hepatitis C virus management,” Current Opinion in HIV and AIDS, vol. 6, pp. 546–552, 2011.
[21]
M. L. C. Vachon and D. T. Dieterich, “HIV/HCV-coinfected patient and new treatment options,” Clinics In Liver Disease, vol. 15, pp. 585–596, 2011.
[22]
R. Medzhitov and C. Janeway Jr., “Innate immunity,” The New England Journal of Medicine, vol. 343, pp. 338–344, 2000.
[23]
T. H. Mogensen, “Pathogen recognition and inflammatory signaling in innate immune defenses,” Clinical Microbiology Reviews, vol. 22, no. 2, pp. 240–273, 2009.
[24]
M. Altfeld, L. Fadda, D. Frleta, and N. Bhardwaj, “DCs and NK cells: critical effectors in the immune response to HIV-1,” Nature Reviews Immunology, vol. 11, no. 3, pp. 176–186, 2011.
[25]
V. Piguet and R. M. Steinman, “The interaction of HIV with dendritic cells: outcomes and pathways,” Trends in Immunology, vol. 28, no. 11, pp. 503–510, 2007.
[26]
A. Iwasaki and R. Medzhitov, “Regulation of adaptive immunity by the innate immune system,” Science, vol. 327, no. 5963, pp. 291–295, 2010.
[27]
M. G. Katze Jr., Y. He, and M. Gale Jr., “Viruses and interferon: a fight for supremacy,” Nature Reviews Immunology, vol. 2, no. 9, pp. 675–687, 2002.
[28]
S. Akira, S. Uematsu, and O. Takeuchi, “Pathogen recognition and innate immunity,” Cell, vol. 124, no. 4, pp. 783–801, 2006.
[29]
G. C. Sen, “Viruses and interferons,” Annual Review of Microbiology, vol. 55, pp. 255–281, 2001.
[30]
F. Heil, H. Hemmi, H. Hochrein et al., “Species-specific recognition of single-stranded rna via till-like receptor 7 and 8,” Science, vol. 303, no. 5663, pp. 1526–1529, 2004.
[31]
L. Alexopoulou, A. C. Holt, R. Medzhitov, and R. A. Flavell, “Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3,” Nature, vol. 413, no. 6857, pp. 732–738, 2001.
[32]
O. Takeuchi and S. Akira, “Pattern recognition receptors and inflammation,” Cell, vol. 140, no. 6, pp. 805–820, 2010.
[33]
T. B. Geijtenbeek, D. S. Kwon, R. Torensma et al., “DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells,” Cell, vol. 100, no. 5, pp. 587–597, 2000.
[34]
T. Lehner, Y. Wang, J. Pido-Lopez, T. Whittall, L. A. Bergmeier, and K. Babaahmady, “The emerging role of innate immunity in protection against HIV-1 infection,” Vaccine, vol. 26, no. 24, pp. 2997–3001, 2008.
[35]
L. Hussain and T. Lehner, “Comparative investigation of Langerhans' cells and potential receptors for HIV in oral, genitourinary and rectal epithelia,” Immunology, vol. 85, no. 3, pp. 475–484, 1995.
[36]
F. Groot, T. M. van Capel, M. L. Kapsenberg, B. Berkhout, and E. C. de Jong, “Opposing roles of blood myeloid and plasmacytoid dendritic cells in HIV-1 infection of T cells: transmission facilitation versus replication inhibition,” Blood, vol. 108, no. 6, pp. 1957–1964, 2006.
[37]
J. P. Herbeuval and G. M. Shearer, “HIV-1 immunopathogenesis: how good interferon turns bad,” Clinical Immunology, vol. 123, no. 2, pp. 121–128, 2007.
[38]
M. Colonna, F. Navarro, T. Bellon et al., “A common inhibitory receptor for major histocompatibility complex class I molecules on human lymphoid and myelomonocytic cells,” Journal of Experimental Medicine, vol. 186, no. 11, pp. 1809–1818, 1997.
[39]
F. Cocchi, A. L. DeVico, A. Garzino-Demo, S. K. Arya, R. C. Gallo, and P. Lusso, “Identification of RANTES, MIP-1α, and MIP-1β as the major HIV-suppressive factors produced by CD8+ T cells,” Science, vol. 270, no. 5243, pp. 1811–1815, 1995.
[40]
T. Lehner, Y. Wang, M. Cranage et al., “Up-regulation of β-chemokines and down-modulation of CCR5 co-receptors inhibit simian immunodeficiency virus transmission in non-human primates,” Immunology, vol. 99, no. 4, pp. 569–577, 2000.
[41]
D. A. Ferrick, M. D. Schrenzel, T. Mulvania, B. Hsieh, W. C. Ferlin, and H. Lepper, “Differential production of IFN-γ and IL-4 in response to Th1- and Th2-stimulating pathogens by γδ T cells in vivo,” Nature, vol. 373, no. 6511, pp. 255–257, 1995.
[42]
M. Wallace, S. R. Bartz, W. L. Changs, D. A. Mackenzie, C. D. Pauza, and M. Malkovsky, “γδ T lymphocyte responses to human immuno- deficiency virus,” Clinical & Experimental Immunology, vol. 103, pp. 177–184, 1996.
[43]
L. Sun, C. M. Finnegan, T. Kish-Catalone et al., “Human β-defensins suppress human immunodeficiency virus infection: potential role in mucosal protection,” Journal of Virology, vol. 79, no. 22, pp. 14318–14329, 2005.
[44]
Y. L. Chiu and W. C. Greene, “The APOBEC3 cytidine deaminases: an innate defensive network opposing exogenous retroviruses and endogenous retroelements,” Annual Review of Immunology, vol. 26, pp. 317–353, 2008.
[45]
S. J. Neil, T. Zang, and P. D. Bieniasz, “Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu,” Nature, vol. 451, no. 7177, pp. 425–430, 2008.
[46]
M. W. Yap, S. Nisole, C. Lynch, and J. P. Stoye, “Trim5α protein restricts both HIV-1 and murine leukemia virus,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 29, pp. 10786–10791, 2004.
[47]
T. Hatziioannou, D. Perez-Caballero, A. Yang, S. Cowan, and P. D. Bieniasz, “Retrovirus resistance factors Ref1 and Lv1 are species-specific variants of TRIM5α,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 29, pp. 10774–10779, 2004.
[48]
D. I. Tai, S. L. Tsai, Y. M. Chen et al., “Activation of nuclear factor κB in hepatitis C virus infection: implications for pathogenesis and hepatocarcinogenesis,” Hepatology, vol. 31, no. 3, pp. 656–664, 2000.
[49]
J. T. Guo, J. A. Sohn, Q. Zhu, and C. Seeger, “Mechanism of the interferon alpha response against hepatitis C virus replicons,” Virology, vol. 325, no. 1, pp. 71–81, 2004.
[50]
K. Cheent and S. I. Khakoo, “Natural killer cells and hepatitis C: action and reaction,” Gut, vol. 60, no. 2, pp. 268–278, 2011.
[51]
G. D. Tomaras and B. F. Haynes, “HIV-1-specific antibody responses during acute and chronic HIV-1 infection,” Current Opinion in HIV and AIDS, vol. 4, no. 5, pp. 373–379, 2009.
[52]
M. Rode, S. Balkow, V. Sobek et al., “Perforin and fas act together in the induction of apoptosis, and both are critical in the clearance of lymphocytic choriomeningitis virus infection,” Journal of Virology, vol. 78, no. 22, pp. 12395–12405, 2004.
[53]
S. A. Younes, B. Yassine-Diab, A. R. Dumont et al., “HIV-1 viremia prevents the establishment of interleukin 2-producing HIV-specific memory CD4+ T cells endowed with proliferative capacity,” Journal of Experimental Medicine, vol. 198, no. 12, pp. 1909–1922, 2003.
[54]
C. Dong, “TH17 cells in development: an updated view of their molecular identity and genetic programming,” Nature Reviews Immunology, vol. 8, no. 5, pp. 337–348, 2008.
[55]
A. Prendergast, J. G. Prado, Y. H. Kang et al., “HIV-1 infection is characterized by profound depletion of CD161+ Th17 cells and gradual decline in regulatory T cells,” AIDS, vol. 24, no. 4, pp. 491–502, 2010.
[56]
S. Dandekar, M. D. George, and A. J. B？umler, “Th17 cells, HIV and the gut mucosal barrier,” Current Opinion in HIV and AIDS, vol. 5, no. 2, pp. 173–178, 2010.
[57]
S. Sakaguchi, “Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negative control of immune responses,” Annual Review of Immunology, vol. 22, pp. 531–562, 2004.
[58]
W. Cao, B. D. Jamieson, L. E. Hultin, P. M. Hultin, and R. Detels, “Regulatory T cell expansion and immune activation during untreated HIV type 1 infection are associated with disease progression,” AIDS Research and Human Retroviruses, vol. 25, no. 2, pp. 183–191, 2009.
[59]
J. D. Estes, S. Wietgrefe, T. Schacker et al., “Simian immunodeficiency virus-induced lymphatic tissue fibrosis is mediated by transforming growth factor β1-positive regulatory T cells and begins in early infection,” Journal of Infectious Diseases, vol. 195, no. 4, pp. 551–561, 2007.
[60]
P. A. Apoil, B. Puissant, F. Roubinet, M. Abbal, P. Massip, and A. Blancher, “FOXP3 mRNA levels are decreased in peripheral blood CD4+ lymphocytes from HIV-positive patients,” Journal of Acquired Immune Deficiency Syndromes, vol. 39, no. 4, pp. 381–385, 2005.
[61]
M. P. Eggena, B. Barugahare, N. Jones et al., “Depletion of regulatory T cells in HIV infection is associated with immune activation,” Journal of Immunology, vol. 174, no. 7, pp. 4407–4414, 2005.
[62]
S. Razvi, L. Schneider, M. M. Jonas, and C. Cunningham-Rundles, “Outcome of intravenous immunoglobulin-transmitted hepatitis C virus infection in primary immunodeficiency,” Clinical Immunology, vol. 101, no. 3, pp. 284–288, 2001.
[63]
H. M. Chapel, J. M. Christie, V. Peach, and R. W. G. Chapman, “Five-year follow-up of patients with primary antibody deficiencies following an outbreak of acute hepatitis C,” Clinical Immunology, vol. 99, no. 3, pp. 320–324, 2001.
[64]
M. Chen, M. S？llberg, A. S？nnerborg et al., “Limited humoral immunity in hepatitis C virus infection,” Gastroenterology, vol. 116, no. 1, pp. 135–143, 1999.
[65]
S. L. Tsai, Y. F. Liaw, M. H. Chen, C. Y. Huang, and G. C. Kuo, “Detection of type 2-like T-helper cells in hepatitis C virus infection: implications for hepatitis C virus chronicity,” Hepatology, vol. 25, no. 2, pp. 449–458, 1997.
[66]
P. Farci, H. J. Alter, D. C. Wong et al., “Prevention of hepatitis C virus infection in chimpanzees after antibody-mediated in vitro neutralization,” Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 16, pp. 7792–7796, 1994.
[67]
Y. K. Shimizu, H. Igarashi, T. Kiyohara et al., “A hyperimmune serum against a synthetic peptide corresponding to the hypervariable region 1 of hepatitis C virus can prevent viral infection in cell cultures,” Virology, vol. 223, no. 2, pp. 409–412, 1996.
[68]
P. Farci, A. Shimoda, D. Wong et al., “Prevention of hepatitis C virus infection in chimpanzees by hyperimmune serum against the hypervariable region 1 of the envelope 2 protein,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 26, pp. 15394–15399, 1996.
[69]
Y. K. Shimizu, M. Hijikata, A. Iwamoto, H. J. Alter, R. H. Purcell, and H. Yoshikura, “Neutralizing antibodies against hepatitis C virus and the emergence of neutralization escape mutant viruses,” Journal of Virology, vol. 68, no. 3, pp. 1494–1500, 1994.
[70]
K. Yamaguchi, E. Tanaka, K. Higashi et al., “Adaptation of hepatitis C virus for persistent infection in patients with acute hepatitis,” Gastroenterology, vol. 106, no. 5, pp. 1344–1348, 1994.
[71]
K. Bj？ro, S. S. Fr？land, Z. Yun, H. H. Samdal, and T. Haaland, “Hepatitis C infection in patients with primary hypogammaglobulinemia after treatment with contaminated immune globulin,” The New England Journal of Medicine, vol. 331, no. 24, pp. 1607–1611, 1994.
[72]
E. C. Shin, U. Seifert, T. Kato et al., “Virus-induced type I IFN stimulates generation of immunoproteasomes at the site of infection,” Journal of Clinical Investigation, vol. 116, no. 11, pp. 3006–3014, 2006.
[73]
R. Thimme, J. Bukh, H. C. Spangenberg et al., “Viral and immunological determinants of hepatitis C virus clearance, persistence, and disease,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 24, pp. 15661–15668, 2002.
[74]
H. M. Diepolder, R. Zachoval, R. M. Hoffmann et al., “Possible mechanism involving T-lymphocyte response to non-structural protein 3 in viral clearance in acute hepatitis C virus infection,” The Lancet, vol. 346, no. 8981, pp. 1006–1007, 1995.
[75]
F. Lechner, D. K. Wong, P. R. Dunbar et al., “Analysis of successful immune responses in persons infected with hepatitis C virus,” Journal of Experimental Medicine, vol. 191, no. 9, pp. 1499–1512, 2000.
[76]
G. M. Lauer, E. Barnes, M. Lucas et al., “High resolution analysis of cellular immune responses in resolved and persistent hepatitis C virus infection,” Gastroenterology, vol. 127, no. 3, pp. 924–936, 2004.
[77]
N. H. Gruner, T. J. Gerlach, M.-C. Jung, et al., “Association of hepatitis C virus-specific CD8+ T cells with viral clearnce in acute hepatitis C,” Journal of Infectious Diseases, vol. 181, pp. 1528–1536, 2000.
[78]
M. Cucchiarini, A. R. Kammer, B. Brahscheid, et al., “Vigorous peripheral blood cytotoxic T cell response during the acute phase of hepatitis C virus infection,” Cellular Immunology, vol. 203, pp. 111–123, 2000.
[79]
S. Cooper, A. L. Erickson, E. J. Adams et al., “Analysis of a successful immune response against hepatitis C virus,” Immunity, vol. 10, no. 4, pp. 439–449, 1999.
[80]
R. Thimme, D. Oldach, K. M. Chang, C. Steiger, S. C. Ray, and F. V. Chisari, “Determinants of viral clearance and persistence during acute hepatitis C virus infection,” Journal of Experimental Medicine, vol. 194, no. 10, pp. 1395–1406, 2001.
[81]
V. Kasprowicz, J. S. Zur Wiesch, T. Kuntzen et al., “High level of PD-1 expression on hepatitis C virus (HCV)-specific CD8+ and CD4+ T cells during acute HCV infection, irrespective of clinical outcome,” Journal of Virology, vol. 82, no. 6, pp. 3154–3160, 2008.
[82]
F. Lechner, D. K. H. Wong, P. R. Dunbar et al., “Analysis of successful immune responses in persons infected with hepatitis C virus,” Journal of Experimental Medicine, vol. 191, no. 9, pp. 1499–1512, 2000.
[83]
S. Urbani, B. Amadei, P. Fisicaro et al., “Outcome of acute hepatitis C is related to virus-specific CD4 function and maturation of antiviral memory CD8 responses,” Hepatology, vol. 44, no. 1, pp. 126–139, 2006.
[84]
R. Wyatt, E. Des Jardins, R. W. Sweet, J. Robinson, W. A. Hendrickson, and J. G. Sodroski, “The antigenic structure of the HIV gp120 envelope glycoprotein,” Nature, vol. 393, no. 6686, pp. 705–711, 1998.
[85]
N. K. Back, L. Smit, J. J. De Jong et al., “An N-glycan within the human immunodeficiency virus type 1？gp120？V3 loop affects virus neutralization,” Virology, vol. 199, no. 2, pp. 431–438, 1994.
[86]
W. Kamp, M. B. Berk, C. J. Visser, and H. S. Nottet, “Mechanisms of HIV-1 to escape from the host immune surveillance,” European Journal of Clinical Investigation, vol. 30, no. 8, pp. 740–746, 2000.
[87]
P. J. Goulder, C. Brander, Y. Tang et al., “Evolution and transmission of stable CTL escape mutations in HIV infection,” Nature, vol. 412, no. 6844, pp. 334–338, 2001.
[88]
Y. Yokomaku, H. Miura, H. Tomiyama et al., “Impaired processing and presentation of cytotoxic-T-lymphocyte (CTL) epitopes are major escape mechanisms from CTL immune pressure in human immunodeficiency virus type 1 infection,” Journal of Virology, vol. 78, no. 3, pp. 1324–1332, 2004.
[89]
N. Gulzar, “CD8+ T-cells: function and response to HIV infection,” Current HIV Research, vol. 2, no. 1, pp. 23–37, 2004.
[90]
M. Lambotin, S. Raghuraman, F. Stoll-Keller, T. F. Baumert, and H. Barth, “A look behind closed doors: interaction of persistent viruses with dendritic cells,” Nature Reviews Microbiology, vol. 8, no. 5, pp. 350–360, 2010.
[91]
B. Liu, A. M. Woltman, H. L. Janssen, and A. Boonstra, “Modulation of dendritic cell function by persistent viruses,” Journal of Leukocyte Biology, vol. 85, no. 2, pp. 205–214, 2009.
[92]
M. J. Gale Jr., M. J. Korth, and M. G. Katze Jr., “Repression of the PKR protein kinase by the hepatitis C virus NS5A protein: a potential mechanism of interferon resistance,” Clinical and Diagnostic Virology, vol. 10, no. 2-3, pp. 157–162, 1998.
[93]
S. Chang, K. Kodys, and G. Szabo, “Impaired expression and function of toll-like receptor 7 in hepatitis C virus infection in human hepatoma cells,” Hepatology, vol. 51, no. 1, pp. 35–42, 2010.
[94]
A. M. Woltman, A. Boonstra, and H. L. Janssen, “Dendritic cells in chronic viral hepatitis B and C: victims or guardian angels?” Gut, vol. 59, no. 1, pp. 115–125, 2010.
[95]
E. J. Ryan and C. O'Farrelly, “The affect of chronic hepatitis C infection on dendritic cell function: a summary of the experimental evidence,” Journal of Viral Hepatitis, vol. 18, no. 9, pp. 601–607, 2011.
[96]
H. Murakami, S. M. F. Akbar, H. Matsui, N. Horiike, and M. Onji, “Decreased interferon-α production and impaired T helper 1 polarization by dendritic cells from patients with chronic hepatitis C,” Clinical and Experimental Immunology, vol. 137, no. 3, pp. 559–565, 2004.
[97]
T. Kanto, M. Inoue, M. Miyazaki et al., “Impaired function of dendritic cells circulating in patients infected with hepatitis C virus who have persistently normal alanine aminotransferase levels,” Intervirology, vol. 49, no. 1-2, pp. 58–63, 2006.
[98]
T. Kanto, M. Inoue, H. Miyatake et al., “Reduced numbers and impaired ability of myeloid and plasmacytoid dendritic cells to polarize T helper cells in chronic hepatitis C virus infection,” Journal of Infectious Diseases, vol. 190, no. 11, pp. 1919–1926, 2004.
[99]
A. Ulsenheimer, J. T. Gerlach, M. C. Jung et al., “Plasmacytoid dendritic cells in acute and chronic hepatitis C virus infection,” Hepatology, vol. 41, no. 3, pp. 643–651, 2005.
[100]
S. Della Bella, A. Crosignani, A. Riva et al., “Decrease and dysfunction of dendritic cells correlate with impaired hepatitis C virus-specific CD4+ T-cell proliferation in patients with hepatitis C virus infection,” Immunology, vol. 121, no. 2, pp. 283–292, 2007.
[101]
R. S. Longman, A. H. Talal, I. M. Jacobson, C. M. Rice, and M. L. Albert, “Normal functional capacity in circulating myeloid and plasmacytoid dendritic cells in patients with chronic hepatitis C,” Journal of Infectious Diseases, vol. 192, no. 3, pp. 497–503, 2005.
[102]
L. Averill, W. M. Lee, and N. J. Karandikar, “Differential dysfunction in dendritic cell subsets during chronic HCV infection,” Clinical Immunology, vol. 123, no. 1, pp. 40–49, 2007.
[103]
R. S. Longman, A. H. Talal, I. M. Jacobson, M. L. Albert, and C. M. Rice, “Presence of functional dendritic cells in patients chronically infected with hepatitis C virus,” Blood, vol. 103, no. 3, pp. 1026–1029, 2004.
[104]
D. Piccioli, S. Tavarini, S. Nuti et al., “Comparable functions of plasmacytoid and monocyte-derived dendritic cells in chronic hepatitis C patients and healthy donors,” Journal of Hepatology, vol. 42, no. 1, pp. 61–67, 2005.
[105]
D. D. Anthony, N. L. Yonkers, A. B. Post et al., “Selective impairments in dendritic cell-associated function distinguish hepatitis C virus and HIV infection,” Journal of Immunology, vol. 172, no. 8, pp. 4907–4916, 2004.
[106]
J. A. Mengshol, L. Golden-Mason, N. Castelblanco, et al., “Impaired plasmacytoid dendritic cell maturation and differential chemotaxis in chronic hepatitis C virus: associations with antiviral treatment outcomes,” Gut, vol. 58, pp. 964–973, 2009.
[107]
S. Crotta, A. Stilla, A. Wack et al., “Inhibition of natural killer cells through engagement of CD81 by the major hepatitis C virus envelope protein,” Journal of Experimental Medicine, vol. 195, no. 1, pp. 35–41, 2002.
[108]
C. T. Tseng and G. R. Klimpel, “Binding of the hepatitis C virus envelope protein E2 to CD81 inhibits natural killer cell functions,” Journal of Experimental Medicine, vol. 195, no. 1, pp. 43–49, 2002.
[109]
L. Golden-Mason and H. R. Rosen, “Natural killer cells: primary target for hepatitis C virus immune evasion strategies?” Liver Transplantation, vol. 12, no. 3, pp. 363–372, 2006.
[110]
R. Liu, W. A. Paxton, S. Choe et al., “Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection,” Cell, vol. 86, no. 3, pp. 367–377, 1996.
[111]
D. den Uyl, I. E. van der Horst-Bruinsma, and M. van Agtmael, “Progression of HIV to AIDS: a protective role for HLA-B27?” AIDS Reviews, vol. 6, no. 2, pp. 89–96, 2004.
[112]
H. Streeck, M. Lichterfeld, G. Alter et al., “Recognition of a defined region within p24 GAG by CD8+ T cells during primary human immunodeficiency virus type 1 infection in individuals expressing protective HLA class I alleles,” Journal of Virology, vol. 81, no. 14, pp. 7725–7731, 2007.
[113]
A. McMichael, “T cell responses and viral escape,” Cell, vol. 93, no. 5, pp. 673–676, 1998.
[114]
I. P. Keet, J. Tang, M. R. Klein et al., “Consistent associations of HLA class I and II and transporter gene products with progression of human immunodeficiency virus type 1 infection in homosexual men,” Journal of Infectious Diseases, vol. 180, no. 2, pp. 299–309, 1999.
[115]
H. Hendel, S. Caillat-Zucman, H. Lebuanec et al., “New class I and II HLA alleles strongly associated with opposite patterns of progression to AIDS,” Journal of Immunology, vol. 162, no. 11, pp. 6942–6946, 1999.
[116]
S. P. Buchbinder, M. H. Katz, N. A. Hessol, P. M. O'Malley, and S. D. Holmberg, “Long-term HIV-1 infection without immunologic progression,” AIDS, vol. 8, no. 8, pp. 1123–1128, 1994.
[117]
P. J. Easterbrook, “Long-term non-progression in HIV infection: definitions and epidemiological issues,” Journal of Infection, vol. 38, no. 2, pp. 71–73, 1999.
[118]
R. A. Kaslow, M. Carrington, R. Apple et al., “Influence of combinations of human major histocompatibility complex genes on the course of HIV-1 infection,” Nature Medicine, vol. 2, no. 4, pp. 405–411, 1996.
[119]
M. Magierowska, I. Theodorou, P. Debré et al., “Combined genotypes of CCR5, CCR2, SDF1, and HLA genes can predict the long-term nonprogressor status in human immunodeficiency virus-1-infected individuals,” Blood, vol. 93, no. 3, pp. 936–941, 1999.
[120]
E. Trachtenberg, B. Korber, C. Sollars et al., “Advantage of rare HLA supertype in HIV disease progression,” Nature Medicine, vol. 9, no. 7, pp. 928–935, 2003.
[121]
P. J. Goulder and D. I. Watkins, “HIV and SIV CTL escape: implications for vaccine design,” Nature Reviews Immunology, vol. 4, no. 8, pp. 630–640, 2004.
[122]
A. Pontillo, L. A. Brandao, R. L. Guimaraes, L. Segat, E. Athanasakis, and S. A. Crovella, “3'UTR SNP in NLRP3 gene is associated with susceptibility to HIV-1 infection,” Journal of Acquired Immune Deficiency Syndromes, vol. 54, pp. 236–240, 2010.
[123]
P. Y. Bochud, M. Hersberger, P. Taffé, et al., “Polymorphisms in Toll-like receptor 9 influence the clinical course of HIV-1 infection,” AIDS, vol. 21, pp. 441–446, 2007.
[124]
S. O. Pine, M. J. McElrath, and P. Y. Bochud, “Polymorphisms in toll-like receptor 4 and toll-like receptor 9 influence viral load in a seroincident cohort of HIV-1-infected individuals,” AIDS, vol. 23, no. 18, pp. 2387–2395, 2009.
[125]
D. Y. Oh, K. Baumann, O. Hamouda et al., “A frequent functional toll-like receptor 7 polymorphism is associated with accelerated HIV-1 disease progression,” AIDS, vol. 23, no. 3, pp. 297–307, 2009.
[126]
A. Meier, J. J. Chang, E. S. Chan et al., “Sex differences in the Toll-like receptor-mediated response of plasmacytoid dendritic cells to HIV-1,” Nature Medicine, vol. 15, no. 8, pp. 955–959, 2009.
[127]
H. Farzadegan, D. R. Hoover, J. Astemborski et al., “Sex differences in HIV-1 viral load and progression to AIDS,” The Lancet, vol. 352, no. 9139, pp. 1510–1514, 1998.
[128]
M. W. Fried, M. L. Shiffman, K. R. Reddy et al., “Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection,” The New England Journal of Medicine, vol. 347, no. 13, pp. 975–982, 2002.
[129]
J. Nattermann, L. Leifeld, and U. Spengler, “Host genetic factors and treatment of hepatitis C,” Current Molecular Pharmacology, vol. 1, no. 2, pp. 171–180, 2008.
[130]
L. J. Yee, “Host genetic determinants in hepatitis C virus infection,” Genes and Immunity, vol. 5, no. 4, pp. 237–245, 2004.
[131]
R. Singh, R. Kaul, A. Kaul, and K. Khan, “A comparative review of HLA associates with hepatitis B and C viral infections across global populations,” World Journal of Gastroenterology, vol. 13, no. 12, pp. 1770–1787, 2007.
[132]
D. Ge, J. Fellay, A. J. Thompson et al., “Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance,” Nature, vol. 461, no. 7262, pp. 399–401, 2009.
[133]
V. Suppiah, M. Moldovan, G. Ahlenstiel et al., “IL28B is associated with response to chronic hepatitis C interferon-α and ribavirin therapy,” Nature Genetics, vol. 41, no. 10, pp. 1100–1104, 2009.
[134]
A. Balagopal, D. L. Thomas, and C. L. Thio, “IL28B and the control of hepatitis C virus infection,” Gastroenterology, vol. 139, no. 6, pp. 1865–1876, 2010.
[135]
Y. Tanaka, N. Nishida, M. Sugiyama et al., “Genome-wide association of IL28B with response to pegylated interferon-α and ribavirin therapy for chronic hepatitis C,” Nature Genetics, vol. 41, no. 10, pp. 1105–1109, 2009.
[136]
R. Lopez-Rodriguez, M. Trapero-Marugan, M. J. Borque, et al., “Genetic variants of interferon-stimulated genes and IL-28B as host prognostic factors of response to combination treatment for chronic hepatitis C,” Clinical Pharmacology & Therapeutics, vol. 90, pp. 712–721, 2011.
[137]
H. M. Diepolder, J. T. Gerlach, R. Zachoval et al., “Immunodominant CD4+ T-cell epitope within nonstructural protein 3 in acute hepatitis C virus infection,” Journal of Virology, vol. 71, no. 8, pp. 6011–6019, 1997.
[138]
V. Lamonaca, G. Missale, S. Urbani et al., “Conserved hepatitis C virus sequences are highly immunogenic for CD4+ T cells: implications for vaccine development,” Hepatology, vol. 30, no. 4, pp. 1088–1098, 1999.
[139]
S. Barrett, M. Sweeney, and J. Crowe, “Host immune responses in hepatitis C virus clearance,” European Journal of Gastroenterology & Hepatology, vol. 17, pp. 1089–1097, 2005.
[140]
S. I. Khakoo, C. L. Thio, M. P. Martin et al., “HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection,” Science, vol. 305, no. 5685, pp. 872–874, 2004.
[141]
S. Knapp, U. Warshow, D. Hegazy et al., “Consistent beneficial effects of killer cell immunoglobulin-like receptor 2Dl3 and group 1 human leukocyte antigen-c following exposure to hepatitis c virus,” Hepatology, vol. 51, no. 4, pp. 1168–1175, 2010.
[142]
J. R. Vidal-Casti？eira, A. López-Vázquez, R. Díaz-Pe？a et al., “Effect of killer immunoglobulin-like receptors in the response to combined treatment in patients with chronic hepatitis C virus infection,” Journal of Virology, vol. 84, no. 1, pp. 475–481, 2010.
[143]
L. Fadda, G. Borhis, P. Ahmed et al., “Peptide antagonism as a mechanism for NK cell activation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 22, pp. 10160–10165, 2010.
[144]
A. K. Moesta, P. J. Norman, M. Yawata, N. Yawata, M. Gleimer, and P. Parham, “Synergistic polymorphism at two positions distal to the ligand-binding site makes KIR2DL2 a stronger receptor for HLA-C Than KIR2DL3,” Journal of Immunology, vol. 180, no. 6, pp. 3969–3979, 2008.
[145]
D. Schulte, M. Vogel, B. Langhans et al., “The HLA-ER/HLA-ER genotype affects the natural course of hepatitis C virus (HCV) infection and is associated with HLA-E-Restricted recognition of an HCV-Derived peptide by interferon-γ-secreting human CD8+ T cells,” Journal of Infectious Diseases, vol. 200, no. 9, pp. 1397–1401, 2009.
[146]
R. K. Strong, M. A. Holmes, P. Li, L. Braun, N. Lee, and D. E. Geraghty, “HLA-E allelic variants: correlating differential expression, peptide affinities, crystal structures, and thermal stabilities,” Journal of Biological Chemistry, vol. 278, no. 7, pp. 5082–5090, 2003.
[147]
S. M. McKiernan, R. Hagan, M. Curry et al., “Distinct MHC class I and II alleles are associated with hepatitis C viral clearance, originating from a single source,” Hepatology, vol. 40, no. 1, pp. 108–114, 2004.
[148]
C. Neumann-Haefelin, S. McKiernan, S. Ward et al., “Dominant influence of an HLA-B27 restricted CD8+ T cell response in mediating HCV clearance and evolution,” Hepatology, vol. 43, no. 3, pp. 563–572, 2006.
[149]
R. Sawhney and K. Visvanathan, “Polymorphisms of toll-like receptors and their pathways in viral hepatitis,” Antiviral Therapy, vol. 16, no. 4, pp. 443–458, 2011.
[150]
S. Knapp, B. J. W. Hennig, A. J. Frodsham et al., “Interleukin-10 promoter polymorphisms and the outcome of hepatitis C virus infection,” Immunogenetics, vol. 55, no. 6, pp. 362–369, 2003.
[151]
A. Mangia, R. Santoro, M. Piattelli et al., “IL-10 haplotypes as possible predictors of spontaneous clearance of HCV infection,” Cytokine, vol. 25, no. 3, pp. 103–109, 2004.
[152]
T. Kimura, T. Saito, M. Yoshimura et al., “Association of transforming growth factor-β1 functional polymorphisms with natural clearance of hepatitis C virus,” Journal of Infectious Diseases, vol. 193, no. 10, pp. 1371–1374, 2006.
