1887

Abstract

Effective host immune responses are essential for the control of hepatitis C virus (HCV) infection and persistence of HCV has indeed been attributed to their failure. In recent years, several and experimental models have allowed studies of host immune responses against HCV. Numerous observations derived from these models have improved our understanding of the mechanisms responsible for the host's ability to clear the virus as well as of the mechanisms responsible for the host's failure to control HCV replication. Importantly, several findings obtained with these model systems have been confirmed in studies of acutely or chronically HCV-infected individuals. Collectively, several mechanisms are used by HCV to escape host immune responses, such as poor induction of the innate immune response and escaping/impairing adaptive immunity. In this review, we summarize current findings from experimental models available for studies of the immune response targeting HCV and discuss the relevance of these findings for the situation in HCV-infected humans.

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2011-03-01
2024-12-05
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References

  1. Ahlenstiel, G., Titerence, R. H., Koh, C., Edlich, B., Feld, J. J., Rotman, Y., Ghany, M. G., Hoofnagle, J. H., Liang, T. J. & other authors(2010). Natural killer cells are polarized towards cytotoxicity in chronic hepatitis C in an interferon-α-dependent manner. Gastroenterology 138, 325–335.[CrossRef] [Google Scholar]
  2. Amadei, B., Urbani, S., Cazaly, A., Fisicaro, P., Zerbini, A., Ahmed, P., Missale, G., Ferrari, C. & Khakoo, S. I.(2010). Activation of natural killer cells during acute infection with hepatitis C virus. Gastroenterology 138, 1536–1545.[CrossRef] [Google Scholar]
  3. Amako, Y., Tsukiyama-Kohara, K., Katsume, A., Hirata, Y., Sekiguchi, S., Tobita, Y., Hayashi, Y., Hishima, T., Funata, N. & other authors(2010). Pathogenesis of hepatitis C virus infection in Tupaia belangeri. J Virol 84, 303–311.[CrossRef] [Google Scholar]
  4. Anthony, D. D., Yonkers, N. L., Post, A. B., Asaad, R., Heinzel, F. P., Lederman, M. M., Lehmann, P. V. & Valdez, H.(2004). Selective impairments in dendritic cell-associated function distinguish hepatitis C virus and HIV infection. J Immunol 172, 4907–4916.[CrossRef] [Google Scholar]
  5. Arnaud, N., Dabo, S., Maillard, P., Budkowska, A., Kalliampakou, K. I., Mavromara, P., Garcin, D., Hugon, J., Gatignol, A. & other authors(2010). Hepatitis C virus controls interferon production through PKR activation. PLoS ONE 5, e10575.[CrossRef] [Google Scholar]
  6. Auffermann-Gretzinger, S., Keeffe, E. B. & Levy, S.(2001). Impaired dendritic cell maturation in patients with chronic, but not resolved, hepatitis C virus infection. Blood 97, 3171–3176.[CrossRef] [Google Scholar]
  7. Bain, C., Fatmi, A., Zoulim, F., Zarski, J. P., Trepo, C. & Inchauspe, G.(2001). Impaired allostimulatory function of dendritic cells in chronic hepatitis C infection. Gastroenterology 120, 512–524.[CrossRef] [Google Scholar]
  8. Balachandran, S., Roberts, P. C., Brown, L. E., Truong, H., Pattnaik, A. K., Archer, D. R. & Barber, G. N.(2000). Essential role for the dsRNA-dependent protein kinase PKR in innate immunity to viral infection. Immunity 13, 129–141.[CrossRef] [Google Scholar]
  9. Banchereau, J., Briere, F., Caux, C., Davoust, J., Lebecque, S., Liu, Y. J., Pulendran, B. & Palucka, K.(2000). Immunobiology of dendritic cells. Annu Rev Immunol 18, 767–811.[CrossRef] [Google Scholar]
  10. Bartenschlager, R. & Sparacio, S.(2007). Hepatitis C virus molecular clones and their replication capacity in vivo and in cell culture. Virus Res 127, 195–207.[CrossRef] [Google Scholar]
  11. Barth, H., Robinet, E., Liang, T. J. & Baumert, T. F.(2008). Mouse models for the study of HCV infection and virus-host interactions. J Hepatol 49, 134–142.[CrossRef] [Google Scholar]
  12. Bartosch, B., Bukh, J., Meunier, J. C., Granier, C., Engle, R. E., Blackwelder, W. C., Emerson, S. U., Cosset, F. L. & Purcell, R. H.(2003).In vitro assay for neutralizing antibody to hepatitis C virus: evidence for broadly conserved neutralization epitopes. Proc Natl Acad Sci U S A 100, 14199–14204.[CrossRef] [Google Scholar]
  13. Bellecave, P., Sarasin-Filipowicz, M., Donze, O., Kennel, A., Gouttenoire, J., Meylan, E., Terracciano, L., Tschopp, J., Sarrazin, C. & other authors(2010). Cleavage of mitochondrial antiviral signaling protein in the liver of patients with chronic hepatitis C correlates with a reduced activation of the endogenous interferon system. Hepatology 51, 1127–1136.[CrossRef] [Google Scholar]
  14. Bigger, C. B., Brasky, K. M. & Lanford, R. E.(2001). DNA microarray analysis of chimpanzee liver during acute resolving hepatitis C virus infection. J Virol 75, 7059–7066.[CrossRef] [Google Scholar]
  15. Bigger, C. B., Guerra, B., Brasky, K. M., Hubbard, G., Beard, M. R., Luxon, B. A., Lemon, S. M. & Lanford, R. E.(2004). Intrahepatic gene expression during chronic hepatitis C virus infection in chimpanzees. J Virol 78, 13779–13792.[CrossRef] [Google Scholar]
  16. Binder, M., Kochs, G., Bartenschlager, R. & Lohmann, V.(2007). Hepatitis C virus escape from the interferon regulatory factor 3 pathway by a passive and active evasion strategy. Hepatology 46, 1365–1374.[CrossRef] [Google Scholar]
  17. Bissig, K. D., Wieland, S. F., Tran, P., Isogawa, M., Le, T. T., Chisari, F. V. & Verma, I. M.(2010). Human liver chimeric mice provide a model for hepatitis B and C virus infection and treatment. J Clin Invest 120, 924–930.[CrossRef] [Google Scholar]
  18. Bitzegeio, J., Bankwitz, D., Hueging, K., Haid, S., Brohm, C., Zeisel, M. B., Herrmann, E., Iken, M., Ott, M. & other authors(2010). Adaptation of hepatitis C virus to mouse CD81 permits infection of mouse cells in the absence of human entry factors. PLoS Pathog 6, e1000978.[CrossRef] [Google Scholar]
  19. Blindenbacher, A., Duong, F. H., Hunziker, L., Stutvoet, S. T., Wang, X., Terracciano, L., Moradpour, D., Blum, H. E., Alonzi, T. & other authors(2003). Expression of hepatitis C virus proteins inhibits interferon alpha signaling in the liver of transgenic mice. Gastroenterology 124, 1465–1475.[CrossRef] [Google Scholar]
  20. Boisvert, J., He, X. S., Cheung, R., Keeffe, E. B., Wright, T. & Greenberg, H. B.(2001). Quantitative analysis of hepatitis C virus in peripheral blood and liver: replication detected only in liver. J Infect Dis 184, 827–835.[CrossRef] [Google Scholar]
  21. Boonstra, A., van der Laan, L. J., Vanwolleghem, T. & Janssen, H. L.(2009). Experimental models for hepatitis C viral infection. Hepatology 50, 1646–1655.[CrossRef] [Google Scholar]
  22. Bowen, D. G. & Walker, C. M.(2005). Adaptive immune responses in acute and chronic hepatitis C virus infection. Nature 436, 946–952.[CrossRef] [Google Scholar]
  23. Bukh, J.(2004). A critical role for the chimpanzee model in the study of hepatitis C. Hepatology 39, 1469–1475.[CrossRef] [Google Scholar]
  24. Bukh, J., Thimme, R., Meunier, J. C., Faulk, K., Spangenberg, H. C., Chang, K. M., Satterfield, W., Chisari, F. V. & Purcell, R. H.(2008). Previously infected chimpanzees are not consistently protected against reinfection or persistent infection after reexposure to the identical hepatitis C virus strain. J Virol 82, 8183–8195.[CrossRef] [Google Scholar]
  25. Burlone, M. E. & Budkowska, A.(2009). Hepatitis C virus cell entry: role of lipoproteins and cellular receptors. J Gen Virol 90, 1055–1070.[CrossRef] [Google Scholar]
  26. Chen, M., Sallberg, M., Sonnerborg, A., Weiland, O., Mattsson, L., Jin, L., Birkett, A., Peterson, D. & Milich, D. R.(1999). Limited humoral immunity in hepatitis C virus infection. Gastroenterology 116, 135–143.[CrossRef] [Google Scholar]
  27. Chen, L., Borozan, I., Feld, J., Sun, J., Tannis, L. L., Coltescu, C., Heathcote, J., Edwards, A. M. & McGilvray, I. D.(2005). Hepatic gene expression discriminates responders and nonresponders in treatment of chronic hepatitis C viral infection. Gastroenterology 128, 1437–1444.[CrossRef] [Google Scholar]
  28. Choo, Q. L., Kuo, G., Weiner, A. J., Overby, L. R., Bradley, D. W. & Houghton, M.(1989). Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 244, 359–362.[CrossRef] [Google Scholar]
  29. Cooper, S., Erickson, A. L., Adams, E. J., Kansopon, J., Weiner, A. J., Chien, D. Y., Houghton, M., Parham, P. & Walker, C. M.(1999). Analysis of a successful immune response against hepatitis C virus. Immunity 10, 439–449.[CrossRef] [Google Scholar]
  30. Cox, A. L., Mosbruger, T., Mao, Q., Liu, Z., Wang, X. H., Yang, H. C., Sidney, J., Sette, A., Pardoll, D. & other authors(2005). Cellular immune selection with hepatitis C virus persistence in humans. J Exp Med 201, 1741–1752.[CrossRef] [Google Scholar]
  31. Crawford, A. & Wherry, E. J.(2009). The diversity of costimulatory and inhibitory receptor pathways and the regulation of antiviral T cell responses. Curr Opin Immunol 21, 179–186.[CrossRef] [Google Scholar]
  32. Dazert, E., Neumann-Haefelin, C., Bressanelli, S., Fitzmaurice, K., Kort, J., Timm, J., McKiernan, S., Kelleher, D., Gruener, N. & other authors(2009). Loss of viral fitness and cross-recognition by CD8+ T cells limit HCV escape from a protective HLA-B27-restricted human immune response. J Clin Invest 119, 376–386. [Google Scholar]
  33. Decalf, J., Fernandes, S., Longman, R., Ahloulay, M., Audat, F., Lefrerre, F., Rice, C. M., Pol, S. & Albert, M. L.(2007). Plasmacytoid dendritic cells initiate a complex chemokine and cytokine network and are a viable drug target in chronic HCV patients. J Exp Med 204, 2423–2437.[CrossRef] [Google Scholar]
  34. Diepolder, H. M., Zachoval, R., Hoffmann, R. M., Wierenga, E. A., Santantonio, T., Jung, M. C., Eichenlaub, D. & Pape, G. R.(1995). Possible mechanism involving T-lymphocyte response to non-structural protein 3 in viral clearance in acute hepatitis C virus infection. Lancet 346, 1006–1007.[CrossRef] [Google Scholar]
  35. Dolganiuc, A., Chang, S., Kodys, K., Mandrekar, P., Bakis, G., Cormier, M. & Szabo, G.(2006). Hepatitis C virus (HCV) core protein-induced, monocyte-mediated mechanisms of reduced IFN-alpha and plasmacytoid dendritic cell loss in chronic HCV infection. J Immunol 177, 6758–6768.[CrossRef] [Google Scholar]
  36. Dolganiuc, A., Paek, E., Kodys, K., Thomas, J. & Szabo, G.(2008). Myeloid dendritic cells of patients with chronic HCV infection induce proliferation of regulatory T lymphocytes. Gastroenterology 135, 2119–2127.[CrossRef] [Google Scholar]
  37. Dowd, K. A., Netski, D. M., Wang, X. H., Cox, A. L. & Ray, S. C.(2009). Selection pressure from neutralizing antibodies drives sequence evolution during acute infection with hepatitis C virus. Gastroenterology 136, 2377–2386.[CrossRef] [Google Scholar]
  38. Ebihara, T., Shingai, M., Matsumoto, M., Wakita, T. & Seya, T.(2008). Hepatitis C virus-infected hepatocytes extrinsically modulate dendritic cell maturation to activate T cells and natural killer cells. Hepatology 48, 48–58.[CrossRef] [Google Scholar]
  39. Eksioglu, E. A., Bess, J. R., Zhu, H., Xu, Y., Dong, H. J., Elyar, J., Nelson, D. R. & Liu, C.(2010). Hepatitis C virus modulates human monocyte-derived dendritic cells. J Viral Hepat 17, 757–769.[CrossRef] [Google Scholar]
  40. Erickson, A. L., Houghton, M., Choo, Q. L., Weiner, A. J., Ralston, R., Muchmore, E. & Walker, C. M.(1993). Hepatitis C virus-specific CTL responses in the liver of chimpanzees with acute and chronic hepatitis C. J Immunol 151, 4189–4199. [Google Scholar]
  41. Erickson, A. L., Kimura, Y., Igarashi, S., Eichelberger, J., Houghton, M., Sidney, J., McKinney, D., Sette, A., Hughes, A. L. & other authors(2001). The outcome of hepatitis C virus infection is predicted by escape mutations in epitopes targeted by cytotoxic T lymphocytes. Immunity 15, 883–895.[CrossRef] [Google Scholar]
  42. Erickson, A. K., Seiwert, S. & Gale, M., Jr(2008). Antiviral potency analysis and functional comparison of consensus interferon, interferon-α2a and pegylated interferon-α2b against hepatitis C virus infection. Antivir Ther 13, 851–862. [Google Scholar]
  43. Farci, P., Shimoda, A., Wong, D., Cabezon, T., De Gioannis, D., Strazzera, A., Shimizu, Y., Shapiro, M., Alter, H. J. & Purcell, R. H.(1996). Prevention of hepatitis C virus infection in chimpanzees by hyperimmune serum against the hypervariable region 1 of the envelope 2 protein. Proc Natl Acad Sci U S A 93, 15394–15399.[CrossRef] [Google Scholar]
  44. Farci, P., Shimoda, A., Coiana, A., Diaz, G., Peddis, G., Melpolder, J. C., Strazzera, A., Chien, D. Y., Munoz, S. J. & other authors(2000). The outcome of acute hepatitis C predicted by the evolution of the viral quasispecies. Science 288, 339–344.[CrossRef] [Google Scholar]
  45. Frese, M., Pietschmann, T., Moradpour, D., Haller, O. & Bartenschlager, R.(2001). Interferon-alpha inhibits hepatitis C virus subgenomic RNA replication by an MxA-independent pathway. J Gen Virol 82, 723–733. [Google Scholar]
  46. Frese, M., Schwärzle, V., Barth, K., Krieger, N., Lohmann, V., Mihm, S., Haller, O. & Bartenschlager, R.(2002). Interferon-γ inhibits replication of subgenomic and genomic hepatitis C virus RNAs. Hepatology 35, 694–703.[CrossRef] [Google Scholar]
  47. Fuller, M. J., Shoukry, N. H., Gushima, T., Bowen, D. G., Callendret, B., Campbell, K. J., Hasselschwert, D. L., Hughes, A. L. & Walker, C. M.(2010). Selection-driven immune escape is not a significant factor in the failure of CD4 T cell responses in persistent hepatitis C virus infection. Hepatology 51, 378–387.[CrossRef] [Google Scholar]
  48. Gale, M. J., Jr, Korth, M. J., Tang, N. M., Tan, S. L., Hopkins, D. A., Dever, T. E., Polyak, S. J., Gretch, D. R. & Katze, M. G.(1997). Evidence that hepatitis C virus resistance to interferon is mediated through repression of the PKR protein kinase by the nonstructural 5A protein. Virology 230, 217–227.[CrossRef] [Google Scholar]
  49. Gale, M., Jr, Blakely, C. M., Kwieciszewski, B., Tan, S. L., Dossett, M., Tang, N. M., Korth, M. J., Polyak, S. J., Gretch, D. R. & other authors(1998). Control of PKR protein kinase by hepatitis C virus nonstructural 5A protein: molecular mechanisms of kinase regulation. Mol Cell Biol 18, 5208–5218. [Google Scholar]
  50. Garaigorta, U. & Chisari, F. V.(2009). Hepatitis C virus blocks interferon effector function by inducing protein kinase R phosphorylation. Cell Host Microbe 6, 513–522.[CrossRef] [Google Scholar]
  51. Ge, D., Fellay, J., Thompson, A. J., Simon, J. S., Shianna, K. V., Urban, T. J., Heinzen, E. L., Qiu, P., Bertelsen, A. H. & other authors(2009). Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 461, 399–401.[CrossRef] [Google Scholar]
  52. Geissmann, F., Manz, M. G., Jung, S., Sieweke, M. H., Merad, M. & Ley, K.(2010). Development of monocytes, macrophages, and dendritic cells. Science 327, 656–661.[CrossRef] [Google Scholar]
  53. Gerlach, J. T., Diepolder, H. M., Jung, M. C., Gruener, N. H., Schraut, W. W., Zachoval, R., Hoffmann, R., Schirren, C. A., Santantonio, T. & other authors(1999). Recurrence of hepatitis C virus after loss of virus-specific CD4+ T-cell response in acute hepatitis C. Gastroenterology 117, 933–941.[CrossRef] [Google Scholar]
  54. Golden-Mason, L., Madrigal-Estebas, L., McGrath, E., Conroy, M. J., Ryan, E. J., Hegarty, J. E., O'Farrelly, C. & Doherty, D. G.(2008). Altered natural killer cell subset distributions in resolved and persistent hepatitis C virus infection following single source exposure. Gut 57, 1121–1128.[CrossRef] [Google Scholar]
  55. Goutagny, N., Fatmi, A., De Ledinghen, V., Penin, F., Couzigou, P., Inchauspe, G. & Bain, C.(2003). Evidence of viral replication in circulating dendritic cells during hepatitis C virus infection. J Infect Dis 187, 1951–1958.[CrossRef] [Google Scholar]
  56. Grakoui, A., Shoukry, N. H., Woollard, D. J., Han, J. H., Hanson, H. L., Ghrayeb, J., Murthy, K. K., Rice, C. M. & Walker, C. M.(2003). HCV persistence and immune evasion in the absence of memory T cell help. Science 302, 659–662.[CrossRef] [Google Scholar]
  57. Grebely, J., Conway, B., Raffa, J. D., Lai, C., Krajden, M. & Tyndall, M. W.(2006). Hepatitis C virus reinfection in injection drug users. Hepatology 44, 1139–1145.[CrossRef] [Google Scholar]
  58. Haller, O. & Weber, F.(2007). Pathogenic viruses: smart manipulators of the interferon system. Curr Top Microbiol Immunol 316, 315–334. [Google Scholar]
  59. Han, J. Q. & Barton, D. J.(2002). Activation and evasion of the antiviral 2′-5′ oligoadenylate synthetase/ribonuclease L pathway by hepatitis C virus mRNA. RNA 8, 512–525.[CrossRef] [Google Scholar]
  60. Helbig, K. J., Lau, D. T., Semendric, L., Harley, H. A. & Beard, M. R.(2005). Analysis of ISG expression in chronic hepatitis C identifies viperin as a potential antiviral effector. Hepatology 42, 702–710.[CrossRef] [Google Scholar]
  61. Hinson, E. R. & Cresswell, P.(2009). The antiviral protein, viperin, localizes to lipid droplets via its N-terminal amphipathic alpha-helix. Proc Natl Acad Sci U S A 106, 20452–20457.[CrossRef] [Google Scholar]
  62. Jo, J., Aichele, U., Kersting, N., Klein, R., Aichele, P., Bisse, E., Sewell, A. K., Blum, H. E., Bartenschlager, R. & other authors(2009). Analysis of CD8+ T-cell-mediated inhibition of hepatitis C virus replication using a novel immunological model. Gastroenterology 136, 1391–1401.[CrossRef] [Google Scholar]
  63. Jones, C. T., Catanese, M. T., Law, L. M., Khetani, S. R., Syder, A. J., Ploss, A., Oh, T. S., Schoggins, J. W., MacDonald, M. R. & other authors(2010). Real-time imaging of hepatitis C virus infection using a fluorescent cell-based reporter system. Nat Biotechnol 28, 167–171.[CrossRef] [Google Scholar]
  64. Kang, J. I., Kwon, S. N., Park, S. H., Kim, Y. K., Choi, S. Y., Kim, J. P. & Ahn, B. Y.(2009). PKR protein kinase is activated by hepatitis C virus and inhibits viral replication through translational control. Virus Res 142, 51–56.[CrossRef] [Google Scholar]
  65. Kanto, T., Hayashi, N., Takehara, T., Tatsumi, T., Kuzushita, N., Ito, A., Sasaki, Y., Kasahara, A. & Hori, M.(1999). Impaired allostimulatory capacity of peripheral blood dendritic cells recovered from hepatitis C virus-infected individuals. J Immunol 162, 5584–5591. [Google Scholar]
  66. Kato, T., Date, T., Miyamoto, M., Furusaka, A., Tokushige, K., Mizokami, M. & Wakita, T.(2003). Efficient replication of the genotype 2a hepatitis C virus subgenomic replicon. Gastroenterology 125, 1808–1817.[CrossRef] [Google Scholar]
  67. Kremsdorf, D. & Brezillon, N.(2007). New animal models for hepatitis C viral infection and pathogenesis studies. World J Gastroenterol 13, 2427–2435.[CrossRef] [Google Scholar]
  68. Lai, W. K., Curbishley, S. M., Goddard, S., Alabraba, E., Shaw, J., Youster, J., McKeating, J. & Adams, D. H.(2007). Hepatitis C is associated with perturbation of intrahepatic myeloid and plasmacytoid dendritic cell function. J Hepatol 47, 338–347.[CrossRef] [Google Scholar]
  69. Lambotin, M., Baumert, T. F. & Barth, H.(2010). Distinct intracellular trafficking of hepatitis C virus in myeloid and plasmacytoid dendritic cells. J Virol 84, 8964–8969.[CrossRef] [Google Scholar]
  70. Larkin, J., Boost, A., Glass, J. I. & Tan, S.-L.(2006). Cytokine-activated natural killer cells exert direct killing of hepatoma cells harboring hepatitis C virus replicons. J Interferon Cytokine Res 26, 854–865.[CrossRef] [Google Scholar]
  71. Larsson, M., Babcock, E., Grakoui, A., Shoukry, N., Lauer, G., Rice, C., Walker, C. & Bhardwaj, N.(2004). Lack of phenotypic and functional impairment in dendritic cells from chimpanzees chronically infected with hepatitis C virus. J Virol 78, 6151–6161.[CrossRef] [Google Scholar]
  72. Lauer, G. M. & Walker, B. D.(2001). Hepatitis C virus infection. N Engl J Med 345, 41–52.[CrossRef] [Google Scholar]
  73. Lechner, F., Wong, D. K. H., Dunbar, P. R., Chapman, R., Chung, R. T., Dohrenwend, P., Robbins, G., Phillips, R., Klenerman, P. & other authors(2000). Analysis of successful immune responses in persons infected with hepatitis C virus. J Exp Med 191, 1499–1512.[CrossRef] [Google Scholar]
  74. Lerat, H., Rumin, S., Habersetzer, F., Berby, F., Trabaud, M. A., Trepo, C. & Inchauspe, G.(1998).In vivo tropism of hepatitis C virus genomic sequences in hematopoietic cells: influence of viral load, viral genotype, and cell phenotype. Blood 91, 3841–3849. [Google Scholar]
  75. Li, Y., Zhang, T., Ho, C., Orange, J. S., Douglas, S. D. & Ho, W. Z.(2004). Natural killer cells inhibit hepatitis C virus expression. J Leukoc Biol 76, 1171–1179.[CrossRef] [Google Scholar]
  76. Li, K., Foy, E., Ferreon, J. C., Nakamura, M., Ferreon, A. C., Ikeda, M., Ray, S. C., Gale, M., Jr & Lemon, S. M.(2005). Immune evasion by hepatitis C virus NS3/4A protease-mediated cleavage of the Toll-like receptor 3 adaptor protein TRIF. Proc Natl Acad Sci U S A 102, 2992–2997.[CrossRef] [Google Scholar]
  77. Liang, H., Russell, R. S., Yonkers, N. L., McDonald, D., Rodriguez, B., Harding, C. V. & Anthony, D. D.(2009). Differential effects of hepatitis C virus JFH1 on human myeloid and plasmacytoid dendritic cells. J Virol 83, 5693–5707.[CrossRef] [Google Scholar]
  78. Lindenbach, B. D., Meuleman, P., Ploss, A., Vanwolleghem, T., Syder, A. J., McKeating, J. A., Lanford, R. E., Feinstone, S. M., Major, M. E. & other authors(2006). Cell culture-grown hepatitis C virus is infectious in vivo and can be recultured in vitro. Proc Natl Acad Sci U S A 103, 3805–3809.[CrossRef] [Google Scholar]
  79. Liu, Y. J., Kanzler, H., Soumelis, V. & Gilliet, M.(2001). Dendritic cell lineage, plasticity and cross-regulation. Nat Immunol 2, 585–589.[CrossRef] [Google Scholar]
  80. Liu, C., Zhu, H., Tu, Z., Xu, Y.-L. & Nelson, D. R.(2003). CD8+ T-cell interaction with HCV replicon cells: evidence for both cytokine- and cell-mediated antiviral activity. Hepatology 37, 1335–1342.[CrossRef] [Google Scholar]
  81. Liu, L., Fisher, B. E., Dowd, K. A., Astemborski, J., Cox, A. L. & Ray, S. C.(2010). Acceleration of hepatitis C virus envelope evolution in humans is consistent with progressive humoral immune selection during the transition from acute to chronic infection. J Virol 84, 5067–5077.[CrossRef] [Google Scholar]
  82. Ljunggren, H. G. & Karre, K.(1985). Host resistance directed selectively against H-2-deficient lymphoma variants. Analysis of the mechanism. J Exp Med 162, 1745–1759.[CrossRef] [Google Scholar]
  83. Logvinoff, C., Major, M. E., Oldach, D., Heyward, S., Talal, A., Balfe, P., Feinstone, S. M., Alter, H., Rice, C. M. & other authors(2004). Neutralizing antibody response during acute and chronic hepatitis C virus infection. Proc Natl Acad Sci U S A 101, 10149–10154.[CrossRef] [Google Scholar]
  84. Lohmann, V., Körner, F., Koch, J., Herian, U., Theilmann, L. & Bartenschlager, R.(1999). Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line. Science 285, 110–113.[CrossRef] [Google Scholar]
  85. Longman, R. S., Talal, A. H., Jacobson, I. M., Albert, M. L. & Rice, C. M.(2004). Presence of functional dendritic cells in patients chronically infected with hepatitis C virus. Blood 103, 1026–1029. [Google Scholar]
  86. Luquin, E., Larrea, E., Civeira, M. P., Prieto, J. & Aldabe, R.(2007). HCV structural proteins interfere with interferon-alpha Jak/STAT signalling pathway. Antiviral Res 76, 194–197.[CrossRef] [Google Scholar]
  87. Major, M. E., Mihalik, K., Fernandez, J., Seidman, J., Kleiner, D., Kolykhalov, A. A., Rice, C. M. & Feinstone, S. M.(1999). Long-term follow-up of chimpanzees inoculated with the first infectious clone for hepatitis C virus. J Virol 73, 3317–3325. [Google Scholar]
  88. Major, M. E., Mihalik, K., Puig, M., Rehermann, B., Nascimbeni, M., Rice, C. M. & Feinstone, S. M.(2002). Previously infected and recovered chimpanzees exhibit rapid responses that control hepatitis C virus replication upon rechallenge. J Virol 76, 6586–6595.[CrossRef] [Google Scholar]
  89. Major, M. E., Dahari, H., Mihalik, K., Puig, M., Rice, C. M., Neumann, A. U. & Feinstone, S. M.(2004). Hepatitis C virus kinetics and host responses associated with disease and outcome of infection in chimpanzees. Hepatology 39, 1709–1720.[CrossRef] [Google Scholar]
  90. Marcello, T., Grakoui, A., Barba-Spaeth, G., Machlin, E. S., Kotenko, S. V., MacDonald, M. R. & Rice, C. M.(2006). Interferons alpha and lambda inhibit hepatitis C virus replication with distinct signal transduction and gene regulation kinetics. Gastroenterology 131, 1887–1898.[CrossRef] [Google Scholar]
  91. Marukian, S., Jones, C. T., Andrus, L., Evans, M. J., Ritola, K. D., Charles, E. D., Rice, C. M. & Dustin, L. B.(2008). Cell culture-produced hepatitis C virus does not infect peripheral blood mononuclear cells. Hepatology 48, 1843–1850.[CrossRef] [Google Scholar]
  92. Matheoud, D., Perie, L., Hoeffel, G., Vimeux, L., Parent, I., Maranon, C., Bourdoncle, P., Renia, L., Prevost-Blondel, A. & other authors(2010). Cross-presentation by dendritic cells from live cells induces protective immune responses in vivo. Blood 115, 4412–4420.[CrossRef] [Google Scholar]
  93. Mehta, S. H., Cox, A., Hoover, D. R., Wang, X. H., Mao, Q., Ray, S., Strathdee, S. A., Vlahov, D. & Thomas, D. L.(2002). Protection against persistence of hepatitis C. Lancet 359, 1478–1483.[CrossRef] [Google Scholar]
  94. Mengshol, J. A., Golden-Mason, L., Castelblanco, N., Im, K. A., Dillon, S. M., Wilson, C. C. & Rosen, H. R.(2009). Impaired plasmacytoid dendritic cell maturation and differential chemotaxis in chronic hepatitis C virus: associations with antiviral treatment outcomes. Gut 58, 964–973.[CrossRef] [Google Scholar]
  95. Mercer, D. F., Schiller, D. E., Elliott, J. F., Douglas, D. N., Hao, C., Rinfret, A., Addison, W. R., Fischer, K. P., Churchill, T. A. & other authors(2001). Hepatitis C virus replication in mice with chimeric human livers. Nat Med 7, 927–933.[CrossRef] [Google Scholar]
  96. Meylan, E., Curran, J., Hofmann, K., Moradpour, D., Binder, M., Bartenschlager, R. & Tschopp, J.(2005). Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature 437, 1167–1172.[CrossRef] [Google Scholar]
  97. Missale, G., Bertoni, R., Lamonaca, V., Valli, A., Massari, M., Mori, C., Rumi, M. G., Houghton, M., Fiaccadori, F. & other authors(1996). Different clinical behaviors of acute hepatitis C virus infection are associated with different vigor of the anti-viral cell-mediated immune response. J Clin Invest 98, 706–714.[CrossRef] [Google Scholar]
  98. Mizukoshi, E., Nascimbeni, M., Blaustein, J. B., Mihalik, K., Rice, C. M., Liang, T. J., Feinstone, S. M. & Rehermann, B.(2002). Molecular and immunological significance of chimpanzee major histocompatibility complex haplotypes for hepatitis C virus immune response and vaccination studies. J Virol 76, 6093–6103.[CrossRef] [Google Scholar]
  99. Moradpour, D., Penin, F. & Rice, C. M.(2007). Replication of hepatitis C virus. Nat Rev Microbiol 5, 453–463.[CrossRef] [Google Scholar]
  100. Muchmore, E., Popper, H., Peterson, D. A., Miller, M. F. & Lieberman, H. M.(1988). Non-A, non-B hepatitis-related hepatocellular carcinoma in a chimpanzee. J Med Primatol 17, 235–246. [Google Scholar]
  101. Mueller, M., Spangenberg, H. C., Kersting, N., Altay, T., Blum, H. E., Klenerman, P., Thimme, R. & Semmo, N.(2010). Virus-specific CD4+ T cell responses in chronic HCV infection in blood and liver identified by antigen-specific upregulation of CD154. J Hepatol 52, 800–811. [Google Scholar]
  102. Mullins, L. J. & Mullins, J. J.(2004). Insights from the rat genome sequence. Genome Biol 5, 221.[CrossRef] [Google Scholar]
  103. Muratori, L., Gibellini, D., Lenzi, M., Cataleta, M., Muratori, P., Morelli, M. C. & Bianchi, F. B.(1996). Quantification of hepatitis C virus-infected peripheral blood mononuclear cells by in situ reverse transcriptase-polymerase chain reaction. Blood 88, 2768–2774. [Google Scholar]
  104. Nakamoto, N., Kaplan, D. E., Coleclough, J., Li, Y., Kaminski, M., Shaked, A., Olthoff, K., Gostick, E., Price, D. A. & other authors(2008). Functional restoration of HCV-specific CD8 T-cells by PD1 blockade is defined by PD1 expression and compartmentalization. Gastroenterology 134, 1927–1937.[CrossRef] [Google Scholar]
  105. Nattermann, J., Zimmermann, H., Iwan, A., von Lilienfeld-Toal, M., Leifeld, L., Nischalke, H. D., Langhans, B., Sauerbruch, T. & Spengler, U.(2006). Hepatitis C virus E2 and CD81 interaction may be associated with altered trafficking of dendritic cells in chronic hepatitis C. Hepatology 44, 945–954.[CrossRef] [Google Scholar]
  106. Neumann-Haefelin, C., Blum, H. E., Chisari, F. V. & Thimme, R.(2005). T cell response in hepatitis C virus infection. J Clin Virol 32, 75–85.[CrossRef] [Google Scholar]
  107. Neumann-Haefelin, C., Timm, J., Spangenberg, H. C., Wischniowski, N., Nazarova, N., Kersting, N., Roggendorf, M., Allen, T. M., Blum, H. E. & other authors(2008). Virological and immunological determinants of intrahepatic virus-specific CD8+ T-cell failure in chronic hepatitis C virus infection. Hepatology 47, 1824–1836.[CrossRef] [Google Scholar]
  108. Ohira, M., Ishiyama, K., Tanaka, Y., Doskali, M., Igarashi, Y., Tashiro, H., Hiraga, N., Imamura, M., Sakamoto, N. & other authors(2009). Adoptive immunotherapy with liver allograft-derived lymphocytes induces anti-HCV activity after liver transplantation in humans and humanized mice. J Clin Invest 119, 3226–3235. [Google Scholar]
  109. Oliviero, B., Varchetta, S., Paudice, E., Michelone, G., Zaramella, M., Mavilio, D., De Filippi, F., Bruno, S. & Mondelli, M. U.(2009). Natural killer cell functional dichotomy in chronic hepatitis B and chronic hepatitis C virus infections. Gastroenterology 137, 1151–1160.[CrossRef] [Google Scholar]
  110. Osugi, Y., Vuckovic, S. & Hart, D. N.(2002). Myeloid blood CD11c+ dendritic cells and monocyte-derived dendritic cells differ in their ability to stimulate T lymphocytes. Blood 100, 2858–2866.[CrossRef] [Google Scholar]
  111. Pal, S., Sullivan, D. G., Kim, S., Lai, K. K., Kae, J., Cotler, S. J., Carithers, R. L., Jr, Wood, B. L., Perkins, J. D. & other authors(2006). Productive replication of hepatitis C virus in perihepatic lymph nodes in vivo: implications of HCV lymphotropism. Gastroenterology 130, 1107–1116.[CrossRef] [Google Scholar]
  112. Patzwahl, R., Meier, V., Ramadori, G. & Mihm, S.(2001). Enhanced expression of interferon-regulated genes in the liver of patients with chronic hepatitis C virus infection: detection by suppression-subtractive hybridization. J Virol 75, 1332–1338.[CrossRef] [Google Scholar]
  113. Pedersen, I. M., Cheng, G., Wieland, S., Volinia, S., Croce, C. M., Chisari, F. V. & David, M.(2007). Interferon modulation of cellular microRNAs as an antiviral mechanism. Nature 449, 919–922.[CrossRef] [Google Scholar]
  114. Pestka, J. M., Zeisel, M. B., Blaser, E., Schurmann, P., Bartosch, B., Cosset, F. L., Patel, A. H., Meisel, H., Baumert, J. & other authors(2007). Rapid induction of virus-neutralizing antibodies and viral clearance in a single-source outbreak of hepatitis C. Proc Natl Acad Sci U S A 104, 6025–6030.[CrossRef] [Google Scholar]
  115. Pietschmann, T., Zayas, M., Meuleman, P., Long, G., Appel, N., Koutsoudakis, G., Kallis, S., Leroux-Roels, G., Lohmann, V. & other authors(2009). Production of infectious genotype 1b virus particles in cell culture and impairment by replication enhancing mutations. PLoS Pathog 5, e1000475.[CrossRef] [Google Scholar]
  116. Ploss, A. & Rice, C. M.(2009). Towards a small animal model for hepatitis C. EMBO Rep 10, 1220–1227.[CrossRef] [Google Scholar]
  117. Ploss, A., Khetani, S. R., Jones, C. T., Syder, A. J., Trehan, K., Gaysinskaya, V. A., Mu, K., Ritola, K., Rice, C. M. & other authors(2010). Persistent hepatitis C virus infection in microscale primary human hepatocyte cultures. Proc Natl Acad Sci U S A 107, 3141–3145.[CrossRef] [Google Scholar]
  118. Podevin, P., Carpentier, A., Pene, V., Aoudjehane, L., Carriere, M., Zaidi, S., Hernandez, C., Calle, V., Meritet, J. F. & other authors(2010). Production of infectious hepatitis C virus in primary cultures of human adult hepatocytes. Gastroenterology 139, 1355–1364.[CrossRef] [Google Scholar]
  119. Rauch, A., Kutalik, Z., Descombes, P., Cai, T., Di Iulio, J., Mueller, T., Bochud, M., Battegay, M., Bernasconi, E. & other authors(2010). Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome-wide association study. Gastroenterology 138, 1338–1345.[CrossRef] [Google Scholar]
  120. Ray, S. C., Fanning, L., Wang, X. H., Netski, D. M., Kenny-Walsh, E. & Thomas, D. L.(2005). Divergent and convergent evolution after a common-source outbreak of hepatitis C virus. J Exp Med 201, 1753–1759.[CrossRef] [Google Scholar]
  121. Robert, F., Kapp, L. D., Khan, S. N., Acker, M. G., Kolitz, S., Kazemi, S., Kaufman, R. J., Merrick, W. C., Koromilas, A. E. & other authors(2006). Initiation of protein synthesis by hepatitis C virus is refractory to reduced eIF2.GTP.Met-tRNA(i)(Met) ternary complex availability. Mol Biol Cell 17, 4632–4644.[CrossRef] [Google Scholar]
  122. Rodrigue-Gervais, I. G., Jouan, L., Beaule, G., Sauve, D., Bruneau, J., Willems, B., Sekaly, R. P. & Lamarre, D.(2007). Poly(I:C) and lipopolysaccharide innate sensing functions of circulating human myeloid dendritic cells are affected in vivo in hepatitis C virus-infected patients. J Virol 81, 5537–5546.[CrossRef] [Google Scholar]
  123. Rollier, C., Drexhage, J. A., Verstrepen, B. E., Verschoor, E. J., Bontrop, R. E., Koopman, G. & Heeney, J. L.(2003). Chronic hepatitis C virus infection established and maintained in chimpanzees independent of dendritic cell impairment. Hepatology 38, 851–858.[CrossRef] [Google Scholar]
  124. Saito, K., Ait-Goughoulte, M., Truscott, S. M., Meyer, K., Blazevic, A., Abate, G., Ray, R. B., Hoft, D. F. & Ray, R.(2008a). Hepatitis C virus inhibits cell surface expression of HLA-DR, prevents dendritic cell maturation, and induces interleukin-10 production. J Virol 82, 3320–3328.[CrossRef] [Google Scholar]
  125. Saito, T., Owen, D. M., Jiang, F., Marcotrigiano, J. & Gale, M., Jr(2008b). Innate immunity induced by composition-dependent RIG-I recognition of hepatitis C virus RNA. Nature 454, 523–527.[CrossRef] [Google Scholar]
  126. Salloum, S., Oniangue-Ndza, C., Neumann-Haefelin, C., Hudson, L., Giugliano, S., aus dem Siepen, M., Nattermann, J., Spengler, U., Lauer, G. M. & other authors(2008). Escape from HLA-B*08-restricted CD8 T cells by hepatitis C virus is associated with fitness costs. J Virol 82, 11803–11812.[CrossRef] [Google Scholar]
  127. Sarasin-Filipowicz, M., Oakeley, E. J., Duong, F. H., Christen, V., Terracciano, L., Filipowicz, W. & Heim, M. H.(2008). Interferon signaling and treatment outcome in chronic hepatitis C. Proc Natl Acad Sci U S A 105, 7034–7039.[CrossRef] [Google Scholar]
  128. Sarasin-Filipowicz, M., Krol, J., Markiewicz, I., Heim, M. H. & Filipowicz, W.(2009). Decreased levels of microRNA miR-122 in individuals with hepatitis C responding poorly to interferon therapy. Nat Med 15, 31–33.[CrossRef] [Google Scholar]
  129. Semmo, N., Day, C. L., Ward, S. M., Lucas, M., Harcourt, G., Loughry, A. & Klenerman, P.(2005). Preferential loss of IL-2-secreting CD4+ T helper cells in chronic HCV infection. Hepatology 41, 1019–1028.[CrossRef] [Google Scholar]
  130. Shepard, C. W., Finelli, L. & Alter, M. J.(2005). Global epidemiology of hepatitis C virus infection. Lancet Infect Dis 5, 558–567.[CrossRef] [Google Scholar]
  131. Shiina, M. & Rehermann, B.(2008). Cell culture-produced hepatitis C virus impairs plasmacytoid dendritic cell function. Hepatology 47, 385–395. [Google Scholar]
  132. Shimoike, T., McKenna, S. A., Lindhout, D. A. & Puglisi, J. D.(2009). Translational insensitivity to potent activation of PKR by HCV IRES RNA. Antiviral Res 83, 228–237.[CrossRef] [Google Scholar]
  133. Shoukry, N. H., Grakoui, A., Houghton, M., Chien, D. Y., Ghrayeb, J., Reimann, K. A. & Walker, C. M.(2003). Memory CD8+ T cells are required for protection from persistent hepatitis C virus infection. J Exp Med 197, 1645–1655.[CrossRef] [Google Scholar]
  134. Soderholm, J., Ahlen, G., Kaul, A., Frelin, L., Alheim, M., Barnfield, C., Liljestrom, P., Weiland, O., Milich, D. R. & other authors(2006). Relation between viral fitness and immune escape within the hepatitis C virus protease. Gut 55, 266–274.[CrossRef] [Google Scholar]
  135. Spangenberg, H. C., Viazov, S., Kersting, N., Neumann-Haefelin, C., McKinney, D., Roggendorf, M., von Weizsäcker, F., Blum, H. E. & Thimme, R.(2005). Intrahepatic CD8+ T-cell failure during chronic hepatitis C virus infection. Hepatology 42, 828–837.[CrossRef] [Google Scholar]
  136. Stamataki, Z., Grove, J., Balfe, P. & McKeating, J. A.(2008). Hepatitis C virus entry and neutralization. Clin Liver Dis 12, 693–712.[CrossRef] [Google Scholar]
  137. Stamataki, Z., Shannon-Lowe, C., Shaw, J., Mutimer, D., Rickinson, A. B., Gordon, J., Adams, D. H., Balfe, P. & McKeating, J. A.(2009). Hepatitis C virus association with peripheral blood B lymphocytes potentiates viral infection of liver-derived hepatoma cells. Blood 113, 585–593.[CrossRef] [Google Scholar]
  138. Stegmann, K. A., Bjorkstrom, N. K., Liermann, H., Ciesek, S., Riese, P., Wiegand, J., Hadem, J., Suneetha, P. V., Jaroszewicz, J. & other authors(2010). Interferon alpha induces TRAIL on natural killer cells is associated with control of hepatitis C virus infection. Gastroenterology 138, 1885–1897.[CrossRef] [Google Scholar]
  139. Su, A. I., Pezacki, J. P., Wodicka, L., Brideau, A. D., Supekova, L., Thimme, R., Wieland, S., Bukh, J., Purcell, R. H. & other authors(2002). Genomic analysis of the host response to hepatitis C virus infection. Proc Natl Acad Sci U S A 99, 15669–15674.[CrossRef] [Google Scholar]
  140. Suppiah, V., Moldovan, M., Ahlenstiel, G., Berg, T., Weltman, M., Abate, M. L., Bassendine, M., Spengler, U., Dore, G. J. & other authors(2009). IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat Genet 41, 1100–1104.[CrossRef] [Google Scholar]
  141. Takahashi, K., Asabe, S., Wieland, S., Garaigorta, U., Gastaminza, P., Isogawa, M. & Chisari, F. V.(2010). Plasmacytoid dendritic cells sense hepatitis C virus-infected cells, produce interferon, and inhibit infection. Proc Natl Acad Sci U S A 107, 7431–7436.[CrossRef] [Google Scholar]
  142. Tanaka, Y., Nishida, N., Sugiyama, M., Kurosaki, M., Matsuura, K., Sakamoto, N., Nakagawa, M., Korenaga, M., Hino, K. & other authors(2009). Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet 41, 1105–1109.[CrossRef] [Google Scholar]
  143. Taylor, D. R., Shi, S. T., Romano, P. R., Barber, G. N. & Lai, M. M.(1999). Inhibition of the interferon-inducible protein kinase PKR by HCV E2 protein. Science 285, 107–110.[CrossRef] [Google Scholar]
  144. Taylor, D. R., Puig, M., Darnell, M. E., Mihalik, K. & Feinstone, S. M.(2005). New antiviral pathway that mediates hepatitis C virus replicon interferon sensitivity through ADAR1. J Virol 79, 6291–6298.[CrossRef] [Google Scholar]
  145. Terenin, I. M., Dmitriev, S. E., Andreev, D. E. & Shatsky, I. N.(2008). Eukaryotic translation initiation machinery can operate in a bacterial-like mode without eIF2. Nat Struct Mol Biol 15, 836–841.[CrossRef] [Google Scholar]
  146. Tester, I., Smyk-Pearson, S., Wang, P., Wertheimer, A., Yao, E., Lewinsohn, D. M., Tavis, J. E. & Rosen, H. R.(2005). Immune evasion versus recovery after acute hepatitis C virus infection from a shared source. J Exp Med 201, 1725–1731.[CrossRef] [Google Scholar]
  147. Thimme, R., Oldach, D., Chang, K.-M., Steiger, C., Ray, S. C. & Chisari, F. V.(2001). Determinants of viral clearance and persistence during acute hepatitis C virus infection. J Exp Med 194, 1395–1406.[CrossRef] [Google Scholar]
  148. Thimme, R., Bukh, J., Spangenberg, H. C., Wieland, S., Pemberton, J., Steiger, C., Govindarajan, S., Purcell, R. H. & Chisari, F. V.(2002). Viral and immunological determinants of hepatitis C virus clearance, persistence, and disease. Proc Natl Acad Sci U S A 99, 15661–15668.[CrossRef] [Google Scholar]
  149. Thomas, D. L., Thio, C. L., Martin, M. P., Qi, Y., Ge, D., O'Huigin, C., Kidd, J., Kidd, K., Khakoo, S. I. & other authors(2009). Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature 461, 798–801.[CrossRef] [Google Scholar]
  150. Timm, J., Lauer, G. M., Kavanagh, D. G., Sheridan, I., Kim, A. Y., Lucas, M., Pillay, T., Ouchi, K., Reyor, L. L. & other authors(2004). CD8 epitope escape and reversion in acute HCV infection. J Exp Med 200, 1593–1604.[CrossRef] [Google Scholar]
  151. Timpe, J. M., Stamataki, Z., Jennings, A., Hu, K., Farquhar, M. J., Harris, H. J., Schwarz, A., Desombere, I., Roels, G. L. & other authors(2008). Hepatitis C virus cell-cell transmission in hepatoma cells in the presence of neutralizing antibodies. Hepatology 47, 17–24. [Google Scholar]
  152. Uebelhoer, L., Han, J. H., Callendret, B., Mateu, G., Shoukry, N. H., Hanson, H. L., Rice, C. M., Walker, C. M. & Grakoui, A.(2008). Stable cytotoxic T cell escape mutation in hepatitis C virus is linked to maintenance of viral fitness. PLoS Pathog 4, e1000143.[CrossRef] [Google Scholar]
  153. Ueno, H., Klechevsky, E., Morita, R., Aspord, C., Cao, T., Matsui, T., Di Pucchio, T., Connolly, J., Fay, J. W. & other authors(2007). Dendritic cell subsets in health and disease. Immunol Rev 219, 118–142.[CrossRef] [Google Scholar]
  154. Ulsenheimer, A., Gerlach, J. T., Gruener, N. H., Jung, M. C., Schirren, C. A., Schraut, W., Zachoval, R., Pape, G. R. & Diepolder, H. M.(2003). Detection of functionally altered hepatitis C virus-specific CD4 T cells in acute and chronic hepatitis C. Hepatology 37, 1189–1198.[CrossRef] [Google Scholar]
  155. Villadangos, J. A. & Young, L.(2008). Antigen-presentation properties of plasmacytoid dendritic cells. Immunity 29, 352–361.[CrossRef] [Google Scholar]
  156. Virgin, H. W., Wherry, E. J. & Ahmed, R.(2009). Redefining chronic viral infection. Cell 138, 30–50.[CrossRef] [Google Scholar]
  157. von Hahn, T., Yoon, J. C., Alter, H., Rice, C. M., Rehermann, B., Balfe, P. & McKeating, J. A.(2007). Hepatitis C virus continuously escapes from neutralizing antibody and T-cell responses during chronic infection in vivo. Gastroenterology 132, 667–678.[CrossRef] [Google Scholar]
  158. Wakita, T., Taya, C., Katsume, A., Kato, J., Yonekawa, H., Kanegae, Y., Saito, I., Hayashi, Y., Koike, M. & other authors(1998). Efficient conditional transgene expression in hepatitis C virus cDNA transgenic mice mediated by the Cre/loxP system. J Biol Chem 273, 9001–9006.[CrossRef] [Google Scholar]
  159. Wakita, T., Katsume, A., Kato, J., Taya, C., Yonekawa, H., Kanegae, Y., Saito, I., Hayashi, Y., Koike, M. & other authors(2000). Possible role of cytotoxic T cells in acute liver injury in hepatitis C virus cDNA transgenic mice mediated by Cre/loxP system. J Med Virol 62, 308–317.[CrossRef] [Google Scholar]
  160. Wakita, T., Pietschmann, T., Kato, T., Date, T., Miyamoto, M., Zhao, Z., Murthy, K., Habermann, A., Kräusslich, H.-G. & other authors(2005). Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nat Med 11, 791–796.[CrossRef] [Google Scholar]
  161. Walters, K. A., Joyce, M. A., Thompson, J. C., Smith, M. W., Yeh, M. M., Proll, S., Zhu, L. F., Gao, T. J., Kneteman, N. M. & other authors(2006). Host-specific response to HCV infection in the chimeric SCID-beige/Alb-uPA mouse model: role of the innate antiviral immune response. PLoS Pathog 2, e59.[CrossRef] [Google Scholar]
  162. Weiner, A., Erickson, A. L., Kansopon, J., Crawford, K., Muchmore, E., Hughes, A. L., Houghton, M. & Walker, C. M.(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, 2755–2759.[CrossRef] [Google Scholar]
  163. Wertheimer, A. M., Bakke, A. & Rosen, H. R.(2004). Direct enumeration and functional assessment of circulating dendritic cells in patients with liver disease. Hepatology 40, 335–345. [Google Scholar]
  164. Windisch, M. P., Frese, M., Kaul, A., Trippler, M., Lohmann, V. & Bartenschlager, R.(2005). Dissecting the interferon-induced inhibition of hepatitis C virus replication by using a novel host cell line. J Virol 79, 13778–13793.[CrossRef] [Google Scholar]
  165. Witteveldt, J., Evans, M. J., Bitzegeio, J., Koutsoudakis, G., Owsianka, A. M., Angus, A. G., Keck, Z. Y., Foung, S. K., Pietschmann, T. & other authors(2009). CD81 is dispensable for hepatitis C virus cell-to-cell transmission in hepatoma cells. J Gen Virol 90, 48–58.[CrossRef] [Google Scholar]
  166. Xie, Z. C., Riezu-Boj, J. I., Lasarte, J. J., Guillen, J., Su, J. H., Civeira, M. P. & Prieto, J.(1998). Transmission of hepatitis C virus infection to tree shrews. Virology 244, 513–520.[CrossRef] [Google Scholar]
  167. Xu, X., Chen, H., Cao, X. & Ben, K.(2007). Efficient infection of tree shrew (Tupaia belangeri) with hepatitis C virus grown in cell culture or from patient plasma. J Gen Virol 88, 2504–2512.[CrossRef] [Google Scholar]
  168. Yonkers, N. L., Rodriguez, B., Milkovich, K. A., Asaad, R., Lederman, M. M., Heeger, P. S. & Anthony, D. D.(2007). TLR ligand-dependent activation of naive CD4 T cells by plasmacytoid dendritic cells is impaired in hepatitis C virus infection. J Immunol 178, 4436–4444.[CrossRef] [Google Scholar]
  169. Yoon, J. C., Shiina, M., Ahlenstiel, G. & Rehermann, B.(2009). Natural killer cell function is intact after direct exposure to infectious hepatitis C virions. Hepatology 49, 12–21.[CrossRef] [Google Scholar]
  170. Zhao, X., Tang, Z. Y., Klumpp, B., Wolff-Vorbeck, G., Barth, H., Levy, S., von Weizsacker, F., Blum, H. E. & Baumert, T. F.(2002). Primary hepatocytes of Tupaia belangeri as a potential model for hepatitis C virus infection. J Clin Invest 109, 221–232.[CrossRef] [Google Scholar]
  171. Zhong, J., Gastaminza, P., Cheng, G., Kapadia, S., Kato, T., Burton, D. R., Wieland, S. F., Uprichard, S. L., Wakita, T. & other authors(2005). Robust hepatitis C virus infection in vitro. Proc Natl Acad Sci U S A 102, 9294–9299.[CrossRef] [Google Scholar]
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