Erratum: Hepatitis C virus evasion of adaptive immune responses: A model for viral persistence (Immunologic Research DOI: 10.1007/s12026-009-8152-3);Hepatitis C virus evasion of adaptive immune responses: A model for viral persistence

Immunologic Research

Volumn 47, Issue 1-3, 2010, Pages 216-227

  Burke, Kelly P ^a   Cox, Andrea L ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

CD8 T cell; Epitope variant; Hepatitis C virus; Viral escape; Viral immunity

Indexed keywords

CELL SURFACE RECEPTOR; EPITOPE; PROGRAMMED DEATH 1 RECEPTOR; NEUTRALIZING ANTIBODY;

ADAPTIVE IMMUNITY; CELLULAR IMMUNITY; ENZYME REGULATION; HEPATITIS C; HEPATITIS C VIRUS; IMMUNE RESPONSE; NONHUMAN; PRIORITY JOURNAL; REINFECTION; REVIEW; T LYMPHOCYTE; VIRUS MUTATION; VIRUS STRAIN; ANIMAL; BLOOD; GENETICS; HEPACIVIRUS; HUMAN; IMMUNE EVASION; IMMUNOLOGY; MUTATION; PHYSIOLOGY; VIROLOGY;

ANIMALS; ANTIBODIES, NEUTRALIZING; EPITOPES, T-LYMPHOCYTE; HEPACIVIRUS; HEPATITIS C, CHRONIC; HUMANS; IMMUNE EVASION; MUTATION; T-LYMPHOCYTES;

EID: 77953960796     PISSN: 0257277X     EISSN: None     Source Type: Journal    
DOI: 10.1007/s12026-010-8161-2     Document Type: Erratum

References (72)

1. World Health Organization. Hepatitis C: global prevalence. Wkly Epidemiol Rec. 1997;72:341-8.
2. JB Wong GM McQuillan JG McHutchison T Poynard 2000 Estimating future hepatitis C morbidity, mortality, and costs in the United States Am J Public Health 90 1562 1569 10.2105/AJPH.90.10.1562 11029989
3. MJ Alter D Kruszon-Moran OV Nainan GM McQuillan F Gao LA Moyer RA Kaslow HS Margolis 1999 The prevalence of hepatitis C virus infection in the United States, 1988 through 1994 N Engl J Med 341 556 562 10.1056/NEJM199908193410802 10451460 (Pubitemid 29384163)
4. Centers for Disease Control, Prevention 1998 Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease MMWR 47 PR-19 1 39
5. MJ Alter 1995 Epidemiology of hepatitis C in the West Semin Liver Dis 15 5 14 10.1055/s-2007-1007259 7597444
6. SA Villano D Vlahov KE Nelson S Cohn DL Thomas 1999 Persistence of viremia and the importance of long-term follow-up after acute hepatitis C infection Hepatology 29 908 914 10.1002/hep.510290311 10051497
7. J Cao N Sullivan E Desjardin C Parolin J Robinson R Wyatt J Sodroski 1997 Replication and neutralization of human immunodeficiency virus type 1 lacking the V1 and V2 variable loops of the gp120 envelope glycoprotein J Virol 71 9808 9812 9371651 (Pubitemid 27492434)
8. MJ Tong NS El-Farra AR Reikes RL Co 1995 Clinical outcomes after transfusion-associated hepatitis C N Engl J Med 332 1463 1466 10.1056/NEJM199506013322202 7739682
9. S Cooper AL Erickson EJ Adams J Kansopon AJ Weiner DY Chien M Houghton P Parham CM Walker 1999 Analysis of a successful immune response against hepatitis C virus Immunity 10 439 449 10.1016/S1074-7613(00)80044-8 10229187 (Pubitemid 29205480)
10. NH Gruner TJ Gerlach MC Jung HM Diepolder CA Schirren WW Schraut R Hoffmann R Zachoval T Santantonio M Cucchiarini A Cerny GR Pape 2000 Association of hepatitis C virus-specific CD8+ T cells with viral clearance in acute hepatitis C J Infect Dis 181 1528 1536 10.1086/315450 10823750 (Pubitemid 30387741)
11. F Lechner DK Wong PR Dunbar R Chapman RT Chung P Dohrenwend G Robbins R Phillips P Klenerman BD Walker 2000 Analysis of successful immune responses in persons infected with hepatitis C virus J Exp Med 191 1499 1512 10.1084/jem.191.9.1499 10790425 (Pubitemid 30257347)
12. A Takaki M Wiese G Maertens E Depla U Seifert A Liebetrau JL Miller MP Manns B Rehermann 2000 Cellular immune responses persist and humoral responses decrease two decades after recovery from a single-source outbreak of hepatitis C Nat Med 6 578 582 10.1038/75063 10802716 (Pubitemid 30305910)
13. K Hiroishi H Kita M Kojima H Okamoto T Moriyama T Kaneko T Ishikawa S Ohnishi T Aikawa N Tanaka Y Yazaki K Mitamura M Imawari 1997 Cytotoxic T lymphocyte response and viral load in hepatitis C virus infection Hepatology 25 705 712 10.1002/hep.510250336 9049223 (Pubitemid 27106458)
14. B Rehermann KM Chang JG McHutchison R Kokka M Houghton FV Chisari 1996 Quantitative analysis of the peripheral blood cytotoxic T lymphocyte response in patients with chronic hepatitis C virus infection J Clin Invest 98 1432 1440 10.1172/JCI118931 8823309
15. A Cerny JG McHutchison C Pasquinelli ME Brown MA Brothers B Grabscheid P Fowler M Houghton FV Chisari 1995 Cytotoxic T lymphocyte response to hepatitis C virus-derived peptides containing the HLA A2.1 binding motif J Clin Invest 95 521 530 10.1172/JCI117694 7860734
16. XS He B Rehermann FX Lopez-Labrador J Boisvert R Cheung J Mumm H Wedemeyer M Berenguer TL Wright MM Davis HB Greenberg 1999 Quantitative analysis of hepatitis C virus-specific CD8(+) T cells in peripheral blood and liver using peptide-MHC tetramers Proc Natl Acad Sci USA 96 5692 5697 10.1073/pnas.96.10.5692 10318946 (Pubitemid 29234680)
17. M Shirai H Okada M Nishioka T Akatsuka C Wychowski R Houghten CD Pendleton SM Feinstone JA Berzofsky 1994 An epitope in hepatitis C virus core region recognized by cytotoxic T cells in mice and humans J Virol 68 3334 3342 7512163
18. M Battegay J Fikes AM Di Bisceglie PA Wentworth A Sette E Celis WM Ching A Grakoui CM Rice K Kurokohchi JA Berzofsky JH Hoofnagle SM Feinstone T Akatsuka 1995 Patients with chronic hepatitis C have circulating cytotoxic T cells which recognize hepatitis C virus-encoded peptides binding to HLA-A2.1 molecules J Virol 69 2462 2470 7884894
19. E Foy K Li C Wang R Sumpter Jr M Ikeda SM Lemon M Gale Jr 2003 Regulation of interferon regulatory factor-3 by the hepatitis C virus serine protease Science 300 1145 1148 10.1126/science.1082604 12702807 (Pubitemid 36583099)
20. K Li E Foy JC Ferreon M Nakamura ACM Ferreon M Ikeda SC Ray M Gale SM Lemon 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 USA 102 2992 2997 10.1073/pnas.0408824102 15710891 (Pubitemid 40299904)
21. E Foy K Li R Sumpter Jr YM Loo CL Johnson C Wang PM Fish M Yoneyama T Fujita SM Lemon M Gale Jr 2005 Control of antiviral defenses through hepatitis C virus disruption of retinoic acid-inducible gene-I signaling Proc Natl Acad Sci USA 102 2986 2991 10.1073/pnas.0408707102 15710892 (Pubitemid 40299903)
22. JT Gerlach HM Diepolder MC Jung NH Gruener WW Schraut R Zachoval R Hoffmann CA Schirren T Santantonio GR Pape 1999 Recurrence of hepatitis C virus after loss of virus-specific CD4(+) T-cell response in acute hepatitis C Gastroenterology 117 933 941 10.1016/S0016-5085(99)70353-7 10500077 (Pubitemid 29468237)
23. HR Rosen C Miner AW Sasaki DM Lewinsohn AJ Conrad A Bakke HG Bouwer DJ Hinrichs 2002 Frequencies of HCV-specific effector CD4+ T cells by flow cytometry: correlation with clinical disease stages Hepatology 35 190 198 10.1053/jhep.2002.30293 11786976 (Pubitemid 34032560)
24. A Grakoui NH Shoukry DJ Woollard JH Han HL Hanson J Ghrayeb KK Murthy CM Rice CM Walker 2003 HCV persistence and immune evasion in the absence of memory T cell help Science 302 659 662 10.1126/science.1088774 14576438 (Pubitemid 37310924)
25. NH Shoukry A Grakoui M Houghton DY Chien J Ghrayeb KA Reimann CM Walker 2003 Memory CD8+ T cells are required for protection from persistent hepatitis C virus infection J Exp Med 197 1645 1655 10.1084/jem.20030239 12810686 (Pubitemid 36745340)
26. R Thimme D Oldach KM Chang C Steiger SC Ray FV Chisari 2001 Determinants of viral clearance and persistence during acute hepatitis C virus infection J Exp Med 194 1395 1406 10.1084/jem.194.10.1395 11714747 (Pubitemid 33081515)
27. AL Cox T Mosbruger GM Lauer D Pardoll DL Thomas SC Ray 2005 Comprehensive analyses of CD8+ T cell responses during longitudinal study of acute human hepatitis C Hepatology 42 104 112 10.1002/hep.20749 15962289 (Pubitemid 40911317)
28. NH Gruener F Lechner MC Jung H Diepolder T Gerlach G Lauer B Walker J Sullivan R Phillips GR Pape P Klenerman 2001 Sustained dysfunction of antiviral CD8+ T lymphocytes after infection with hepatitis C virus J Virol 75 5550 5558 10.1128/JVI.75.12.5550-5558.2001 11356962 (Pubitemid 32488148)
29. A Weiner AL Erickson J Kansopon K Crawford E Muchmore AL Hughes M Houghton CM Walker 1995 Persistent hepatitis C virus infection in a chimpanzee is associated with emergence of a cytotoxic T lymphocyte escape variant Proc Natl Acad Sci USA 92 2755 2759 10.1073/pnas.92.7.2755 7708719
30. AU Neumann NP Lam H Dahari DR Gretch TE Wiley TJ Layden AS Perelson 1998 Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy Science 282 103 107 10.1126/science.282.5386.103 9756471 (Pubitemid 28471138)
31. DD Eckels H Wang TH Bian N Tabatabai JC Gill 2000 Immunobiology of hepatitis C virus (HCV) infection: the role of CD4 T cells in HCV infection Immunol Rev 174 90 97 10.1034/j.1600-0528.2002.017403.x 10807509
32. KM Chang B Rehermann JG McHutchison C Pasquinelli S Southwood A Sette FV Chisari 1997 Immunological significance of cytotoxic T lymphocyte epitope variants in patients chronically infected by the hepatitis C virus J Clin Invest 100 2376 2385 10.1172/JCI119778 9410918
33. E Domingo E Martinez-Salas F Sobrino JC de la Torre A Portela J Ortin C Lopez-Galindez P Perez-Brena N Villanueva R Najera 1985 The quasispecies (extremely heterogeneous) nature of viral RNA genome populations: biological relevance-a review Gene 40 1 8 10.1016/0378-1119(85)90017-4 3912262 (Pubitemid 16132020)
34. E Domingo D Sabo T Taniguchi C Weissmann 1978 Nucleotide sequence heterogeneity of an RNA phage population Cell 13 735 744 10.1016/0092-8674(78) 90223-4 657273
35. M Eigen 1971 Self organization of matter and the evolution of biological macromolecules Naturwissenschaften 58 465 523 10.1007/BF00623322 4942363
36. N Kato Y Ootsuyama T Tanaka M Nakagawa T Nakazawa K Muraiso S Ohkoshi M Hijikata K Shimotohno 1992 Marked sequence diversity in the putative envelope proteins of hepatitis C viruses Virus Res 22 107 123 10.1016/0168-1702(92)90038- B 1314471
37. M Martell JI Esteban J Quer J Genesca A Weiner R Esteban J Guardia Gomez 1992 Hepatitis C virus (HCV) circulates as a population of different but closely related genomes: quasispecies nature of HCV genome distribution J Virol 66 3225 3229 1313927
38. SC Ray Q Mao RE Lanford S Bassett O Laeyendecker YM Wang DL Thomas 2000 Hypervariable region 1 sequence stability during hepatitis C virus replication in chimpanzees J Virol 74 3058 3066 10.1128/JVI.74.7.3058-3066.2000 10708420 (Pubitemid 30143728)
39. SC Ray YM Wang O Laeyendecker J Ticehurst SA Villano DL Thomas 1998 Acute hepatitis C virus structural gene sequences as predictors of persistent viremia: hypervariable region 1 as decoy J Virol 73 2938 2946
40. Q Mao SC Ray O Laeyendecker JR Ticehurst SA Strathdee D Vlahov DL Thomas 2001 Human immunodeficiency virus seroconversion and evolution of the hepatitis C virus quasispecies J Virol 75 3259 3267 10.1128/JVI.75.7.3259-3267.2001 11238852 (Pubitemid 32225889)
41. AL Cox T Mosbruger Q Mao Z Liu XH Wang HC Yang J Sidney A Sette D Pardoll DL Thomas SC Ray 2005 Cellular immune selection with hepatitis C virus persistence in humans J Exp Med 201 1741 1752 10.1084/jem.20050121 15939790 (Pubitemid 41002893)
42. F Gonzalez-Candelas MA Bracho A Moya 2003 Molecular epidemiology and forensic genetics: application to a hepatitis C virus transmission event at a hemodialysis unit J Infect Dis 187 352 358 10.1086/367965 12552418 (Pubitemid 36184575)
43. TM Allen M Altfeld XG Yu KM O'Sullivan M Lichterfeld S Le Gall M John BR Mothe PK Lee ET Kalife DE Cohen KA Freedberg DA Strick MN Johnston A Sette ES Rosenberg SA Mallal PJ Goulder C Brander BD Walker 2004 Selection, transmission, and reversion of an antigen-processing cytotoxic T-lymphocyte escape mutation in human immunodeficiency virus type 1 infection J Virol 78 7069 7078 10.1128/JVI.78.13.7069-7078.2004 15194783 (Pubitemid 38781545)
44. J Timm GM Lauer DG Kavanagh I Sheridan AY Kim M Lucas T Pillay K Ouchi LL Reyor JS Zur Wiesch RT Gandhi RT Chung N Bhardwaj P Klenerman BD Walker TM Allen 2004 CD8 epitope escape and reversion in acute HCV infection J Exp Med 200 1593 1604 10.1084/jem.20041006 15611288 (Pubitemid 40094183)
45. Y Kimura T Gushima S Rawale P Kaumaya CM Walker 2005 Escape mutations alter proteasome processing of major histocompatibility complex class I-restricted epitopes in persistent hepatitis C virus infection J Virol 79 4870 4876 10.1128/JVI.79.8.4870-4876.2005 15795272 (Pubitemid 40464237)
46. U Seifert H Liermann V Racanelli A Halenius M Wiese H Wedemeyer T Ruppert K Rispeter P Henklein A Sijts H Hengel PM Kloetzel B Rehermann 2004 Hepatitis C virus mutation affects proteasomal epitope processing J Clin Invest 114 250 259 15254592
47. TM Allen DH O'Connor P Jing JL Dzuris BR Mothe TU Vogel E Dunphy ME Liebl C Emerson N Wilson KJ Kunstman X Wang DB Allison AL Hughes RC Desrosiers JD Altman SM Wolinsky A Sette DI Watkins 2000 Tat-specific cytotoxic T lymphocytes select for SIV escape variants during resolution of primary viraemia Nature 407 386 390 10.1038/35036559 11014195
48. NA Jones X Wei DR Flower M Wong F Michor MS Saag BH Hahn MA Nowak GM Shaw P Borrow 2004 Determinants of human immunodeficiency virus type 1 escape from the primary CD8+ cytotoxic T lymphocyte response J Exp Med 200 1243 1256 10.1084/jem.20040511 15545352 (Pubitemid 39552566)
49. R Draenert S Le Gall KJ Pfafferott AJ Leslie P Chetty C Brander EC Holmes SC Chang ME Feeney MM Addo L Ruiz D Ramduth P Jeena M Altfeld S Thomas Y Tang CL Verrill C Dixon JG Prado P Kiepiela J Martinez-Picado BD Walker PJ Goulder 2004 Immune selection for altered antigen processing leads to cytotoxic T lymphocyte escape in chronic HIV-1 infection J Exp Med 199 905 915 10.1084/jem.20031982 15067030 (Pubitemid 38481082)
50. Y Yokomaku H Miura H Tomiyama A Kawana-Tachikawa M Takiguchi A Kojima Y Nagai A Iwamoto Z Matsuda K Ariyoshi 2004 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 J Virol 78 1324 1332 10.1128/JVI.78.3.1324-1332.2004 14722287 (Pubitemid 38095842)
51. FV Chisari C Ferrari 1995 Hepatitis B virus immunopathogenesis Annul Rev Immunol 13 29 60 10.1146/annurev.iy.13.040195.000333
52. M Wolfl A Rutebemberwa T Mosbruger Q Mao HM Li D Netski SC Ray D Pardoll J Sidney A Sette T Allen T Kuntzen DG Kavanagh J Kuball PD Greenberg AL Cox 2008 Hepatitis C virus immune escape via exploitation of a hole in the T cell repertoire J Immunol 181 6435 6446 18941234
53. T Koibuchi TM Allen M Lichterfeld SK Mui KM O'Sullivan A Trocha SA Kalams RP Johnson BD Walker 2005 Limited sequence evolution within persistently targeted CD8 epitopes in chronic human immunodeficiency virus type 1 infection J Virol 79 8171 8181 10.1128/JVI.79.13.8171-8181.2005 15956562 (Pubitemid 40853520)
54. H Dong G Zhu K Tamada L Chen 1999 B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion Nat Med 5 1365 1369 10.1038/70932 10581077
55. GJ Freeman AJ Long Y Iwai K Bourque T Chernova H Nishimura LJ Fitz N Malenkovich T Okazaki MC Byrne HF Horton L Fouser L Carter V Ling MR Bowman BM Carreno M Collins CR Wood T Honjo 2000 Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation J Exp Med 192 1027 1034 10.1084/jem.192.7.1027 11015443
56. SY Tseng M Otsuji K Gorski X Huang JE Slansky SI Pai A Shalabi T Shin DM Pardoll H Tsuchiya 2001 B7-DC, a new dendritic cell molecule with potent costimulatory properties for T cells J Exp Med 193 839 846 10.1084/jem.193.7.839 11283156 (Pubitemid 32524533)
57. Y Latchman CR Wood T Chernova D Chaudhary M Borde I Chernova Y Iwai AJ Long JA Brown R Nunes EA Greenfield K Bourque VA Boussiotis LL Carter BM Carreno N Malenkovich H Nishimura T Okazaki T Honjo AH Sharpe GJ Freeman 2001 PD-L2 is a second ligand for PD-1 and inhibits T cell activation Nat Immunol 2 261 268 10.1038/85330 11224527 (Pubitemid 33706004)
58. H Radziewicz CC Ibegbu ML Fernandez KA Workowski K Obideen M Wehbi HL Hanson JP Steinberg D Masopust EJ Wherry JD Altman BT Rouse GJ Freeman R Ahmed A Grakoui 2007 Liver-infiltrating lymphocytes in chronic human hepatitis C virus infection display an exhausted phenotype with high levels of PD-1 and low levels of CD127 expression J Virol 81 2545 2553 10.1128/JVI.02021-06 17182670 (Pubitemid 46447020)
59. A Penna M Pilli A Zerbini A Orlandini S Mezzadri L Sacchelli G Missale C Ferrari 2007 Dysfunction and functional restoration of HCV-specific CD8 responses in chronic hepatitis C virus infection Hepatology 45 588 601 10.1002/hep.21541 17326153 (Pubitemid 46450610)
60. S Urbani B Amadei D Tola MC Cavallo S Mezzadri G Missale C Ferrari 2006 PD-1 expression in acute hepatitis C virus infection Hepatology 44 292A 293A 10.1002/hep.21242 (Pubitemid 44049146)
61. A Rutebemberwa SC Ray J Astemborski J Levine L Liu KA Dowd S Clute C Wang A Korman A Sette J Sidney DM Pardoll AL Cox 2008 High-programmed death-1 levels on hepatitis C virus-specific T cells during acute infection are associated with viral persistence and require preservation of cognate antigen during chronic infection J Immunol 181 8215 8225 19050238
62. DL Barber EJ Wherry D Masopust B Zhu JP Allison AH Sharpe GJ Freeman R Ahmed 2006 Restoring function in exhausted CD8 T cells during chronic viral infection Nature 439 682 687 10.1038/nature04444 16382236 (Pubitemid 43237609)
63. Goldberg MV, Maris CH, Hipkiss EL, Flies AS, Zhen L, Tuder RM, Grosso JF, Harris TJ, Getnet D, Whartenby KA, Brockstedt DG, Dubensky TW Jr, Chen L, Pardoll DM, Drake CG. Role of PD-1 and its ligand, B7-H1, in early fate decisions of CD8 T cells. Blood 2007.
64. Petrovas C, Price DA, Mattapallil J, Ambrozak DR, Geldmacher C, Cecchinato V, Vaccari M, Tryniszewska E, Gostick E, Roederer M, Douek DC, Morgan SH, Davis SJ, Franchini G, Koup RA. SIV-specific CD8+ T-cells express high levels of PD1 and cytokines but have impaired proliferative capacity in acute and chronic SIVmac251 infection. Blood, 2007.
65. P Farci HJ Alter S Govindarajan DC Wong R Engle RR Lesniewski IK Mushahwar SM Desai RH Miller N Ogata 1992 Lack of protective immunity against reinfection with hepatitis C virus Science 258 135 140 10.1126/science.1279801 1279801
66. Schulze zur WJ, Lauer GM, Timm J, Kuntzen T, Neukamm M, Berical A, Jones AM, Nolan BE, Longworth SA, Kasprowicz V, McMahon C, Wurcel A, Lohse AW, Lewis-Ximenez LL, Chung RT, Kim AY, Allen TM, Walker BD. Immunologic evidence for lack of heterologous protection following resolution of HCV in subjects with non-genotype 1 infection. Blood, 2007.
67. J Grebely B Conway JD Raffa C Lai M Krajden MW Tyndall 2006 Hepatitis C virus reinfection in injection drug users Hepatology 44 1139 1145 10.1002/hep.21376 17058216 (Pubitemid 44748365)
68. SH Mehta A Cox DR Hoover XH Wang Q Mao S Ray SA Strathdee D Vlahov DL Thomas 2002 Protection against persistence of hepatitis C Lancet 359 1478 1483 10.1016/S0140-6736(02)08435-0 11988247 (Pubitemid 34457766)
69. D Vlahov JC Anthony A Munoz J Margolick KE Nelson DD Celentano L Solomon BF Polk 1991 The ALIVE study, a longitudinal study of HIV-1 infection in intravenous drug users: description of methods and characteristics of participants NIDA Res Monogr 109 75 100 1661376
70. AL Cox DM Netski T Mosbruger SG Sherman S Strathdee D Ompad D Vlahov D Chien V Shyamala SC Ray DL Thomas 2005 Prospective evaluation of community-acquired acute-phase hepatitis C virus infection Clin Infect Dis 40 951 958 10.1086/428578 15824985 (Pubitemid 40418300)
71. KA Dowd DM Netski XH Wang AL Cox SC Ray 2009 Selection pressure from neutralizing antibodies drives sequence evolution during acute infection with hepatitis C virus Gastroenterology 136 2377 2386 10.1053/j.gastro.2009.02.080 19303013
72. Osburn WO, Fisher BE, Dowd KA, Urban G, Liu L, Ray SC, Thomas DL, Cox AL. Spontaneous control of primary hepatitis C virus infection and immunity against persistent reinfection. Gastroenterology 2009; (in press).