2016, Number 1
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Ann Hepatol 2016; 15 (1)
Hepatitis C virus strategies to evade the specific-T cell response: a possible mission favoring its persistence
Quarleri JF, Oubiña JR
Language: English
References: 65
Page: 17-26
PDF size: 305.89 Kb.
ABSTRACT
Hepatitis C virus (HCV) is a small, enveloped RNA virus. The number of HCV-infected individuals worldwide is estimated to be approximately
200 million. The vast majority of HCV infections persist, with up to 80% of all cases leading to chronic hepatitis associated
with liver fibrosis, cirrhosis, and hepatocellular carcinoma. The interaction between HCV and the host have a pivotal role in viral
fitness, persistence, pathogenicity, and disease progression. The control of HCV infection requires both effective innate and adaptive
immune responses. The HCV clearance during acute infection is associated with an early induction of the innate and a delayed initiation
of the adaptive immune responses. However, in the vast majority of acute HCV infections, these responses are overcome and
the virus persistence almost inexorably occurs. Recently, several host- and virus-related mechanisms responsible for the failure of
both the innate and the adaptive immune responses have been recognized. Among the latter, the wide range of escape mutations to
evade the specific-T-and B-cell responses as well as the T cell anergy and the CD8+ T cell exhaustion together with the interference
with its function after prolonged virus exposure hold a pivotal role. Other HCV strategies include the modification or manipulation of
molecules playing key roles in the induction of the interferon response and its induced effector proteins. In this review, we attempt
to gain insights on the main T cell immune evasion strategies used by the virus in order to favor its persistence.
REFERENCES
Samuel CE. Thematic minireview series: elucidating hepatitis C virus-host interactions at the biochemical level. J Biol Chem 2010; 285: 22723-4.
Ireton RC, Gale M, Jr. Pushing to a cure by harnessing innate immunity against hepatitis C virus. Antiviral Res 2014; 108: 156-64.
Holz L, Rehermann B. T cell responses in hepatitis C virus infection: historical overview and goals for future research. Antiviral Res 2015; 114: 96-105.
Wack A, Terczyñska-Dyla E, Hartmann R. Guarding the frontiers: the biology of type III interferons. Nat Immunol 2015; 16: 802-09.
Duggal P, Thio CL, Wojcik GL, Goedert JJ, Mangia A, Latanich R, Kim AY, et al. Genome-wide association study of spontaneous resolution of hepatitis C virus infection: data from multiple cohorts. Ann Intern Med 2013; 158: 235-45.
McFarland AP, Horner SM, Jarret A, Joslyn RC, Bindewald E, Shapiro BA, Delker DA, et al. The favorable IFNL3 genotype escapes mRNA decay mediated by AU-rich elements and hepatitis C virus-induced microRNAs. Nat Immunol 2014; 15: 72-9.
Prokunina-Olsson L, Muchmore B, Tang W, Pfeiffer RM, Park H, Dickensheets H, Hergott D, et al. A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus. Nat Genet 2013; 45: 164-71.
Terczynska-Dyla E, Bibert S, Duong FH, Krol I, Jorgensen S, Collinet E, Kutalik Z, et al. Reduced IFNλ4 activity is associated with improved HCV clearance and reduced expression of interferon-stimulated genes. Nat Commun 2014; 5: 5699.
Rosen HR. Emerging concepts in immunity to hepatitis C virus infection. J Clin Invest 2013; 123: 4121-30.
Shin EC, Park SH, Demino M, Nascimbeni M, Mihalik K, Major M, Veerapu NS, et al. Delayed induction, not impaired recruitment, of specific CD8(+) T cells causes the late onset of acute hepatitis C. Gastroenterology 2011; 14: 686-95.
Claassen MA, Janssen HL, Boonstra A. Role of T cell immunity in hepatitis C virus infections. Curr Opin Virol 2013; 3: 461-7.
Heim MH, Thimme R. Innate and adaptive immune responses in HCV infections. J Hepatol 2014; 61: S14-S25.
Grafmueller S, Billerbeck E, Blum HE, Neumann-Haefelin C, Thimme R. Differential antigen specificity of hepatitis C virusspecific interleukin 17- and interferon gamma-producing CD8(+) T cells during chronic infection. J Infect Dis 2012; 205: 1142-6.
Kuniholm MH, Kovacs A, Gao X, Xue X, Marti D, Thio CL, Peters MG, et al. Specific human leukocyte antigen class I and II alleles associated with hepatitis C virus viremia. Hepatology 2010; 51: 1514-22.
Klenerman P, Thimme R. T cell responses in hepatitis C: the good, the bad and the unconventional. Gut 2012; 61: 1226- 34.
Thimme R, Binder M, Bartenschlager R. Failure of innate and adaptive immune responses in controlling hepatitis C virus infection. FEMS Microbiol Rev 2012; 36: 663-83.
Foster RG, Golden-Mason L, Rutebemberwa A, Rosen HR. Interleukin (IL)-17/IL-22-producing T cells enriched within the liver of patients with chronic hepatitis C viral (HCV) infection. Dig Dis Sci 2012; 57: 381-9.
Lucas M, Ulsenheimer A, Pfafferot K, Heeg MH, Gaudieri S, Gruner N, Rauch A, et al. Tracking virus-specific CD4+ T cells during and after acute hepatitis C virus infection. PLoS One 2007; 2: e649.
Kared H, Fabre T, Bedard N, Bruneau J, Shoukry NH. Galectin- 9 and IL-21 mediate cross-regulation between Th17 and Treg cells during acute hepatitis C. PLoS Pathog 2013; 9: e1003422.
Neumann-Haefelin C, Timm J, Spangenberg HC, Wischniowski N, Nazarova N, Kersting N, Roggendorf M, et al. Virological and immunological determinants of intrahepatic virus-specific CD8+ T-cell failure in chronic hepatitis C virus infection. Hepatology 2008; 47: 1824-36.
Dazert E, Neumann-Haefelin C, Bressanelli S, Fitzmaurice K, Kort J, Timm J, McKiernan S, et al. 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 2009; 119: 376-86.
Ruhl M, Chhatwal P, Strathmann H, Kuntzen T, Bankwitz D, Skibbe K, Walker A, et al. Escape from a dominant HLAB* 15-restricted CD8+ T cell response against hepatitis C virus requires compensatory mutations outside the epitope. J Virol 2012; 86: 991-1000.
Tester I, Smyk-Pearson S, Wang P, Wertheimer A, Yao E, Lewinsohn DM, Tavis JE, et al. Immune evasion versus recovery after acute hepatitis C virus infection from a shared source. J Exp Med 2005; 201: 1725-31.
Fleming VM, Harcourt G, Barnes E, Klenerman P. Virological footprint of CD4+ T-cell responses during chronic hepatitis C virus infection. J Gen Virol 2010; 91: 1396-406.
Larrea E, Riezu-Boj JI, Aldabe R, Guembe L, Echeverria I, Balasiddaiah A, Gastaminza P, et al. Dysregulation of interferon regulatory factors impairs the expression of immunostimulatory molecules in hepatitis C virus genotype 1-infected hepatocytes. Gut 2014; 63: 665-73.
Virgin HW, Wherry EJ, Ahmed R. Redefining chronic viral infection. Cell 2009; 138: 30-50.
Zhao BB, Zheng SJ, Gong LL, Wang Y, Chen CF, Jin WJ, Zhang D, et al. T lymphocytes from chronic HCV-infected patients are primed for activation-induced apoptosis and express unique pro-apoptotic gene signature. PLoS One 2013; 8: e77008.
Lui JB, Devarajan P, Teplicki SA, Chen Z. Cross-differentiation from the CD8 lineage to CD4 T cells in the gut-associated microenvironment with a nonessential role of microbiota. Cell Rep 2015; 10: 574-85.
Seigel B, Bengsch B, Lohmann V, Bartenschlager R, Blum HE, Thimme R. Factors that determine the antiviral efficacy of HCV-specific CD8(+) T cells ex vivo. Gastroenterology 2013; 144: 426-36.
Larrubia JR, Lokhande MU, Garcia-Garzon S, Miquel J, Gonzalez-Praetorius A, Parra-Cid T, Sanz-de-Villalobos E. Persistent hepatitis C virus (HCV) infection impairs HCV-specific cytotoxic T cell reactivity through Mcl-1/Bim imbalance due to CD127 down-regulation. J Viral Hepat 2013; 20: 85-94.
Gupta PK, Godec J, Wolski D, Adland E, Yates K, Pauken KE, Cosgrove C, et al. CD39 expression identifies terminally exhausted CD8+ T Cells. PLoS Pathog 2015; 11: e1005177.
McMahan RH, Golden-Mason L, Nishimura MI, McMahon BJ, Kemper M, Allen TM, Gretch DR, et al. Tim-3 expression on PD-1+ HCV-specific human CTLs is associated with viral persistence, and its blockade restores hepatocyte-directed in vitro cytotoxicity. J Clin Invest 2010; 120: 4546-57.
Kasprowicz V, Schulze Zur Wiesch J, Kuntzen T, Nolan BE, Longworth S, Berical A, Blum J, 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. J Virol 2008; 82: 3154-60.
Wherry EJ, Blattman JN, Murali-Krishna K, van der Most R, Ahmed R. Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment. J Virol 2003; 77: 4911-27.
Shin EC, Park SH, Nascimbeni M, Major M, Caggiari L, de Re V, Feinstone SM, et al. The frequency of CD127(+) hepatitis C virus (HCV)-specific T cells but not the expression of exhaustion markers predicts the outcome of acute HCV infection. J Virol 2013; 87: 4772-7.
Owusu Sekyere S, Suneetha PV, Kraft AR, Zhang S, Dietz J, Sarrazin C, Manns MP, et al. A heterogeneous hierarchy of co-regulatory receptors regulates exhaustion of HCVspecific CD8 T cells in patients with chronic hepatitis C. J Hepatol 2015; 62: 31-40.
Petrovic D, Stamataki Z, Dempsey E, Golden-Mason L, Freeley M, Doherty D, Prichard D, et al. Hepatitis C virus targets the T cell secretory machinery as a mechanism of immune evasion. Hepatology 2011; 53: 1846-53.
Lokhande MU, Thimme R, Klenerman P, Semmo N. Methodologies for the analysis of HCV-specific CD4 T Cells. Front Immunol 2015; 6: 57.
Bhattarai N, McLinden JH, Xiang J, Kaufman TM, Stapleton JT. Conserved motifs within hepatitis C virus envelope (E2) RNA and protein independently inhibit T cell activation. PLoS Pathog 2015; 11: e1005183.
Xiao W, Jiang LF, Deng XZ, Zhu DY, Pei JP, Xu ML, Li BJ, et al. PD-1/PD-L1 signal pathway participates in HCV F proteininduced T cell dysfunction in chronic HCV infection. Immunol Res 2015 [In press].
Vignali DA, Collison LW, Workman CJ. How regulatory T cells work. Nat Rev Immunol 2008; 8: 523-32.
Smyk-Pearson S, Golden-Mason L, Klarquist J, Burton JR, Jr., Tester IA, Wang CC, Culbertson N, et al. Functional suppression by FoxP3+CD4+CD25(high) regulatory T cells during acute hepatitis C virus infection. J Infect Dis 2008; 197: 46-57.
Cusick MF, Schiller JJ, Gill JC, Eckels DD. Hepatitis C virus induces regulatory T cells by naturally occurring viral variants to suppress T cell responses. Clin Dev Immunol 2011: 806061.
Franceschini D, Paroli M, Francavilla V, Videtta M, Morrone S, Labbadia G, Cerino A, et al. PD-L1 negatively regulates CD4+CD25+Foxp3+ Tregs by limiting STAT-5 phosphorylation in patients chronically infected with HCV. J Clin Invest 2009; 119: 551-64.
Qureshi OS, Zheng Y, Nakamura K, Attridge K, Manzotti C, Schmidt EM, Baker J, et al. Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4. Science 2011; 332: 600-3.
Liang B, Workman C, Lee J, Chew C, Dale BM, Colonna L, Flores M, et al. Regulatory T cells inhibit dendritic cells by lymphocyte activation gene-3 engagement of MHC class II. J Immunol 2008; 180: 5916-26.
Dolganiuc A, Kodys K, Kopasz A, Marshall C, Do T, Romics L Jr, Mandrekar P, et al. Hepatitis C virus core and nonstructural protein 3 proteins induce pro- and anti-inflammatory cytokines and inhibit dendritic cell differentiation. J Immunol 2003; 170: 5615-24.
Rodrigue-Gervais IG, Rigsby H, Jouan L, Sauvé D, Sékaly RP, Willems B, Lamarre D. Dendritic cell inhibition is connected to exhaustion of CD8+ T cell polyfunctionality during chronic hepatitis C virus infection. J Immunol 2010; 184: 3134-44.
Krishnadas DK, Ahn JS, Han J, Kumar R, Agrawal B. Immunomodulation by hepatitis C virus-derived proteins: targeting human dendritic cells by multiple mechanisms. Int Immunol 2010; 22: 491-502.
Ebinuma H, Nakamoto N, Li Y, Price DA, Gostick E, Levine BL, Tobias J, et al. Identification and in vitro expansion of functional antigen-specific CD25+ FoxP3+ regulatory T cells in hepatitis C virus infection. J Virol 2008; 82: 5043-53.
Ji XJ, Ma CJ, Wang JM, Wu XY, Niki T, Hirashima M, Moorman JP, et al. HCV-infected hepatocytes drive CD4+ CD25+ Foxp3+ regulatory T-cell development through the Tim-3/Gal- 9 pathway. Eur J Immunol 2013; 43: 458-67.
Sturm N, Thelu MA, Camous X, Dimitrov G, Ramzan M, Dufeu- Duchesne T, Bonorino P, et al. Characterization and role of intra-hepatic regulatory T cells in chronic hepatitis C pathogenesis. J Hepatol 2010; 53: 25-35.
Pelletier S, Drouin C, Bedard N, Khakoo SI, Bruneau J, Shoukry NH. Increased degranulation of natural killer cells during acute HCV correlates with the magnitude of virusspecific T cell responses. J Hepatol 2010; 53: 805-16.
Knapp S, Warshow U, Hegazy D, Brackenbury L, Guha IN, Fowell A, Little AM, 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 2010; 51: 1168-75.
Kokordelis P, Krämer B, Körner C, Boesecke C, Voigt E, Ingiliz P, Glässner A, et al. An effective interferon-gamma-mediated inhibition of hepatitis C virus replication by natural killer cells is associated with spontaneous clearance of acute hepatitis C in human immunodeficiency virus-positive patients. Hepatology 2014; 59: 814-27.
Ahlenstiel G, Titerence RH, Koh C, Edlich B, Feld JJ, Rotman Y, Ghany MG, et al. Natural killer cells are polarized toward cytotoxicity in chronic hepatitis C in an interferon-alfa-dependent manner. Gastroenterology 2010; 138: 325-35.
Oliviero B, Varchetta S, Paudice E, Michelone G, Zaramella M, Mavilio D, De Filippi F, et al. Natural killer cell functional dichotomy in chronic hepatitis B and chronic hepatitis C virus infections. Gastroenterology 2009; 137: 1151-6.
Wang JM, Cheng YQ, Shi L, Ying RS, Wu XY, Li GY, Moorman JP, et al. KLRG1 negatively regulates natural killer cell functions through the Akt pathway in individuals with chronic hepatitis C virus infection. J Virol 2013; 87: 11626-36.
Ding Q, Huang B, Lu J, Liu YJ, Zhong J. Hepatitis C virus NS3/4A protease blocks IL-28 production. Eur J Immunol 2012; 42: 2374-82.
Sene D, Levasseur F, Abel M, Lambert M, Camous X, Hernandez C, Pene V, et al. Hepatitis C virus (HCV) evades NKG2D-dependent NK cell responses through NS5A-mediated imbalance of inflammatory cytokines. PLoS Pathog 2010; 6: e1001184.
Foy E, Li K, Wang C, Sumpter R, Jr., Ikeda M, Lemon SM, Gale M, Jr. Regulation of interferon regulatory factor-3 by the hepatitis C virus serine protease. Science 2003; 300: 1145-8.
Teijaro JR, Ng C, Lee AM, Sullivan BM, Sheehan KC, Welch M, Schreiber RD, et al. Persistent LCMV infection is controlled by blockade of type I interferon signaling. Science 2013; 340: 207-11.
Lee MS, Kim B, Oh GT, Kim YJ. OASL1 inhibits translation of the type I interferon-regulating transcription factor IRF7. Nat Immunol 2013; 14: 346-55.
Lee MS, Park CH, Jeong YH, Kim YJ, Ha SJ. Negative regulation of type I IFN expression by OASL1 permits chronic viral infection and CD8(+) T-cell exhaustion. PLoS Pathog 2013; 9: e1003478.
Kang W, Sung PS, Park SH, Yoon S, Chang DY, Kim S, Han KH, et al. Hepatitis C virus attenuates interferon-induced major histocompatibility complex class I expression and decreases CD8+ T cell effector functions. Gastroenterology 2014; 146: 1351-60.