Skip to main content
Log in

Immune Escape by Hepatitis B Viruses

  • Published:
Virus Genes Aims and scope Submit manuscript

Abstract

Hepatitis B viruses are DNA viruses characterized by their very small genome size and their unique replication via reverse transcription. The circular genome has been efficiently exploited, thereby limiting genome variation, and leaves no space for genes in addition to those essentially needed during the viral live cycle. Hepatitis B viruses are prototype non-cytopathic viruses causing persistent infection. Human hepatitis B virus (HBV), as well as the closely related animal viruses, most frequently are transmitted vertically from mothers to their offspring. Because infection usually persists for many years, if not lifelong, hepatitis B viruses need efficient mechanisms to hide from the immune response of the host. To escape the immune response, they exploit different strategies. Firstly, they use their structural and non-structural proteins multiplely. One of the purposes is to alter the immune response. Secondly, they replicate by establishing a pool of stable extrachromosomal transcription templates, which allow the virus to react sensitively to changes in its microenvironment by up- or downregulating gene expression. Thirdly, hepatitis B viruses replicate in the liver which is an immunopriviledged site.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. WHO, WHO Communicable Series No. 1, 1-26, 1996.

    Google Scholar 

  2. Robinson W.S. in Zakim D. and Boyer T.D. (ed.). Biology of Human Hepatitis Viruses. W. B. Saunders Company, Philadelphia, pp. 1171-1174, 1996.

    Google Scholar 

  3. Chisari F.V. and Ferrari C., Annu Rev Immunol 13, 29-60, 1995.

    PubMed  Google Scholar 

  4. Guidotti L.G., Borrow P., Hobbs M.V., Matzke B., Gresser I., Oldstone M.B., and Chisari F.V., Proc Natl Acad Sci USA 93, 4589-4594, 1996.

    PubMed  Google Scholar 

  5. Rothmann K., Schnolzer M., Radziwill G., Hildt E., Moelling K., and Schaller H., J Virol 72, 10138-10147, 1998.

    PubMed  Google Scholar 

  6. Ganem D. in Fields B.N., Knipe D.M., and Howley P.M. (ed.). Hepadnaviridae: The Viruses and Their Replication. Lippincott-Raven Publishers, Philadelphia, 1996, pp. 2703-2737.

    Google Scholar 

  7. Nassal M. and Schaller H., Trends Microbiol 1, 221-228, 1993.

    PubMed  Google Scholar 

  8. Nassal M. and Schaller H., J Viral Hepat 3, 217-226, 1996.

    PubMed  Google Scholar 

  9. Hu J. and Seeger C., Seminars in Virology 8, 205-211, 1997.

    Google Scholar 

  10. Chisari F.V., Curr Top Microbiol Immunol 206, 149-173, 1996.

    PubMed  Google Scholar 

  11. Ando K., Guidotti L.G., Wirth S., Ishikawa T., Missale G., Moriyama T., Schreiber R.D., Schlicht H.J., Huang S.N., and Chisari F.V., J Immunol 152, 3245-3253, 1994.

    PubMed  Google Scholar 

  12. Nakamoto Y., Guidotti L.G., Kuhlen C.V., Fowler P., and Chisari F.V., J Exp Med 188, 341-350, 1998.

    PubMed  Google Scholar 

  13. Knolle P., Lohr H., Treichel U., Dienes H.P., Lohse A., Schlaack J., and Gerken G., Z Gastroenterol 33, 613-620, 1995.

    PubMed  Google Scholar 

  14. Janeway C.A. and Travers P., Immunobiology. The Immune System in Health and Disease. Current Biology Ltd., London, 1998, pp. 9:1-9:46.

    Google Scholar 

  15. Dienes H.P., Hutteroth T., Hess G., and Meuer S.C., Hepatology 7, 1317-1325, 1987.

    PubMed  Google Scholar 

  16. Zinkernagel R.M. and Hengartner H., Immunol Today 18, 258-260, 1997.

    PubMed  Google Scholar 

  17. Oldstone M.B.A., Curr Top Microbiol Immunol 189, 1-8, 1994.

    PubMed  Google Scholar 

  18. Lohr H.F., Gerken G., Schlicht H.J., Meryer zum Buschenfelde K.H., and Fleischer B., J Infect Dis 168, 1133-1139, 1993.

    PubMed  Google Scholar 

  19. Guidotti L.G., Matzke B., Schaller H., and Chisari F.V., J Virol 69, 6158-6169, 1995.

    PubMed  Google Scholar 

  20. Guidotti L.G., Ishikawa T., Hobbs M.V., Matzke B., Schreiber R., and Chisari F.V., Immunity 4, 25-36, 1996.

    PubMed  Google Scholar 

  21. Chisari F.V., J Clin Invest 99, 1472-1477, 1997.

    PubMed  Google Scholar 

  22. Jilbert A.R. Wu T.T., England J.M., Hall P.M., Carp N.Z., O'Connell A.P., and Mason W.S., J Virol 66, 1377-1388, 1992.

    PubMed  Google Scholar 

  23. Kajino K., Jilbert A.R., Saputelli J., Aldrich C.E., Cullen J., and Mason W.S., J Virol 68, 5792-5803, 1994.

    PubMed  Google Scholar 

  24. Guidotti L.G. and Chisari F.V., Curr Opin Immunol 8, 478-483, 1996.

    PubMed  Google Scholar 

  25. Mason W.S., Cullen J., Moraleda G., Saputelli J., Aldrich C.E., Miller D.S., Tennant B., Frick L., Averett D., Condreay L.D., and Jilbert A.R., Virology 245, 18-32, 1998.

    PubMed  Google Scholar 

  26. Moraleda G., Saputelli J., Aldrich C.E., Averett D., Condreay L., and Mason W.S., J Virol 71, 9392-9399, 1997.

    PubMed  Google Scholar 

  27. Fourel I., Cullen J.M., Saputelli J., Aldrich C.E., Schaffer P., Averett D.R., Pugh J., and Mason W.S., J Virol 68, 8321-8330, 1994.

    PubMed  Google Scholar 

  28. Onji M., Lever A.M., Saito I., and Thomas H.C., Hepatology 9, 92-96, 1989.

    PubMed  Google Scholar 

  29. Foster G.R., Ackrill A.M., Goldin R.D., Kerr I.M., Thomas H.C., and Stark G.R., Proc Natl Acad Sci USA 88, 2888-2892, 1991.

    PubMed  Google Scholar 

  30. Foster G.R., Goldin R.D., Hay A., McGarvey M.J., Stark G.R., and Thomas H.C., Hepatology 17, 757-762, 1993.

    PubMed  Google Scholar 

  31. Whitten T.M., Quets A.T., and Schloemer R.H., J Virol 65, 4699-4704, 1991.

    PubMed  Google Scholar 

  32. Alexander G. and Eddleston A., Lancet 1, 296-297, 1986.

    PubMed  Google Scholar 

  33. Millich D.R., Jones J.E., Hughes J.L., Price J., Raney A.K., and McLachlan A., Proc Natl Acad Sci U S A 87, 6599-6603, 1990.

    PubMed  Google Scholar 

  34. Jamieson B. and R A., Proc Natl Acad Sci USA 85, 2265-2268, 1988.

    PubMed  Google Scholar 

  35. Wisse E. and Knook D.L., Prog Liver Dis 6, 153-171, 1979.

    PubMed  Google Scholar 

  36. Schönrich G., Kalinke U., Momburg F., Malissen M., Schmitt V.A., Malissen B., Hammerling G.J., and Arnold B., Cell 65, 293-304, 1991.

    PubMed  Google Scholar 

  37. Limmer A., Sacher T., Alferink J., Kretschmar M., Schonrich G., Nichterlein T., Arnold B., and Hammerling G.J., Eur J Immunol 28, 2395-2406, 1998.

    PubMed  Google Scholar 

  38. Cantor H. and Dumont A., Nature 215, 744, 1967.

    PubMed  Google Scholar 

  39. Calne R.Y., Nature 223, 472-476, 1969.

    PubMed  Google Scholar 

  40. Callery M.P., Kamei T., and Flye M.W., Transplantation 47, 1092-1094, 1989.

    PubMed  Google Scholar 

  41. Gazzinelli R.T., Wysocka M., Hieny S., Scharton-Kersten T., Cheever A., Kuhn R., Muller W., Trinchieri G., and Sher A., J Immunol 157, 798-805, 1996.

    PubMed  Google Scholar 

  42. Callery M.P., Kamei T., and Flye M.W., Arch Surg 125, 36-40; discussion 31-40, 1990.

    PubMed  Google Scholar 

  43. Bertolino P., Trescol-Biemont M.C., and Rabourdin-Combe C., Eur J Immunol 28, 221-236, 1998.

    PubMed  Google Scholar 

  44. Lohse A.W., Knolle P.A., Bilo K., Uhrig A., Waldmann C., Ibe M., Schmitt E., Gerken G., and Meyer zum Büschenfelde K., Gastroenterology 110, 1175-1181, 1996.

    PubMed  Google Scholar 

  45. Rubinstein D., Roska A.K., and Lipsky P.E., J Immunol 137, 1803-1810, 1986.

    PubMed  Google Scholar 

  46. Knolle P., Schmitt E., Jin S., Germann T., Duchmann R., Hegenbarth S., Gerken G., and Lohse A., Gastroenterology 116, 1428-1440, 1999.

    PubMed  Google Scholar 

  47. Knolle P., Germann T., Treichel U., Uhrig A., Schmitt E., Hegenbarth S., Lohse A., and Gerken G., J Immunol in press, 1999.

  48. Yoffe B., Burns D.K., Bhatt H.S., and Combes B., Hepatology 12, 187-192, 1990.

    PubMed  Google Scholar 

  49. Ando K., Guidotti L.G., Cerny A., Ishikawa T., and Chisari F.V., J Immunol 153, 482-488, 1994.

    PubMed  Google Scholar 

  50. Cavanaugh V.J., Guidotti L.G., and Chisari F.V., J Virol 71, 3236-3243, 1997.

    PubMed  Google Scholar 

  51. Kock J., Theilmann L., Galle P., and Schlicht H.J., Hepatology 23, 405-413, 1996.

    PubMed  Google Scholar 

  52. Stoll-Becker S., Repp R., Glebe D., Schaefer S., Kreuder J., Kann M., Lampert F., and Gerlich W.H., J Virol 71, 5399-5407, 1997.

    PubMed  Google Scholar 

  53. Brind A., Jiang J., Samuel D., Gigou M., Feray C., Brechot C., and Kremsdorf D., J Hepatol 26, 228-235, 1997.

    PubMed  Google Scholar 

  54. Protzer U., Goergen B., Hopf U., Neuhaus P., König V., Meyer zum Büschenfelde K.H., and Gerken G., J Med Virol 50, 135-144, 1996.

    PubMed  Google Scholar 

  55. Mason A., Yoffe B., Noonan C., Mearns M., Campbell C., Kelley A., and Perrillo R.P., Hepatology 16, 36-41, 1992.

    PubMed  Google Scholar 

  56. Rehermann B., Ferrari C., Pasquinelli C., and Chisari F.V., Nat Med 2, 1104-1108, 1996.

    PubMed  Google Scholar 

  57. Penna A., Artini M., Cavalli A., Levrero M., Bertoletti A., Pilli M., Chisari F.V., Rehermann B., Del P.G., Fiaccadori F., and Ferrari C., J Clin Invest 98, 1185-1194, 1996.

    PubMed  Google Scholar 

  58. Barnaba V., Franco A., Alberti A., Benvenuto R., and Balsano F., Nature 345, 258-260, 1990.

    PubMed  Google Scholar 

  59. Schirmbeck R., Melber K., Kuhrober A., Janowicz Z.A., and Reimann J., J Immunol 152, 1110-1119, 1994.

    PubMed  Google Scholar 

  60. Planz O., Seiler P., Hengartner H., and Zinkernagel R.M., Nature 382, 726-729, 1996.

    PubMed  Google Scholar 

  61. Moskophidis D., Lechner F., Pircher H., and Zinkernagel R.M., Nature 362, 758-761, 1993.

    PubMed  Google Scholar 

  62. Gallimore A., Hengartner H., and Zinkernagel R., Immunol Rev 164, 29-36, 1998.

    PubMed  Google Scholar 

  63. Nowak M.A., Bonhoeffer S., Hill A.M., Boehme R., Thomas H.C., and McDade H., Proc Natl Acad Sci USA 93, 4398-4402, 1996.

    PubMed  Google Scholar 

  64. Butz E.A. and Bevan M.J., Immunity 8, 167-175, 1998.

    PubMed  Google Scholar 

  65. Pircher H., Moskophidis D., Rohrer U., Burki K., Hengartner H., and Zinkernagel R.M., Nature 346, 629-633, 1990.

    PubMed  Google Scholar 

  66. Franco A., Ferrari C., Sette A., and Chisari F.V., Curr Opin Immunol 7, 524-531, 1995.

    PubMed  Google Scholar 

  67. Bertoletti A., Sette A., Chisari F.V., Penna A., Levrero M., De C.M., Fiaccadori F., and Ferrari C., Nature 369, 407-410, 1994.

    PubMed  Google Scholar 

  68. Bertoletti A., Costanzo A., Chisari F.V., Levrero M., Artini M., Sette A., Penna A., Giuberti T., Fiaccadori F., and Ferrari C., J Exp Med 180, 933-943, 1994.

    PubMed  Google Scholar 

  69. Klenerman P. and Zinkernagel R.M., Nature 394, 482-485, 1998.

    PubMed  Google Scholar 

  70. Rehermann B., Pasquinelli C., Mosier S.M., and Chisari F.V., J Clin Invest 96, 1527-1534, 1995.

    PubMed  Google Scholar 

  71. Brunetto M.R., Stemler M., Bonino F., Schodel F., Oliveri F., Rizzetto M., Verme G., and Will H., J Hepatol 10, 258-261, 1990.

    PubMed  Google Scholar 

  72. Carman W.F., Jacyna M.R., Hadziyannis S., Karayiannis P., McGarvey M.J., Makris A., and Thomas H.C., Lancet 2, 588-591, 1989.

    Article  PubMed  Google Scholar 

  73. Junker Niepmann M., Bartenschlager R., and Schaller H., Embo J 9, 3389-3396, 1990.

    PubMed  Google Scholar 

  74. Wang G.H. and Seeger C., J Virol 67, 6507-6512, 1993.

    PubMed  Google Scholar 

  75. Protzer U., Trippler M., Ohl J., Knolle P., Duchmann R., Meyer zum Buschenfelde K.H., and Gerken G., J Viral Hepat 3, 155-162, 1996.

    PubMed  Google Scholar 

  76. Lok A.S.F., Akarca U., and Green S., Proc Natl Acad Sci 91, 4077-4081, 1994.

    PubMed  Google Scholar 

  77. Protzer-Knolle U., Knolle P., Schiedhelm E., Meyer zum Büschenfelde K.H., and Gerken G., Arch Virol 141, 2091-2101, 1996.

    PubMed  Google Scholar 

  78. Lai M., Solinas A., Mazzoleni A., Farci P., Lisci V., Porru A., Tocco A., and Balestrieri A., J Hepatol 20, 773-781, 1994.

    PubMed  Google Scholar 

  79. Naumann U., Protzer-Knolle U., Berg T., Leder K., Lobeck H., Bechstein W.O., Gerken G., Hopf U., and Neuhaus P., Hepatology 26, 478-484, 1997.

    PubMed  Google Scholar 

  80. Nassal M. and Rieger A., J Virol 67, 4307-4315, 1993.

    PubMed  Google Scholar 

  81. Schlicht H.J., von B.A., and Theilmann L., Hepatology 13, 57-61, 1991.

    PubMed  Google Scholar 

  82. Milich D.R., Chen M.K., Hughes J.L., and Jones J.E., J Immunol 160, 2013-2021, 1998.

    PubMed  Google Scholar 

  83. Lamberts C., Nassal M., Velhagen I., Zentgraf H., and Schroder C.H., J Virol 67, 3756-3762, 1993.

    PubMed  Google Scholar 

  84. Guidotti L.G., Matzke B., Pasquinelli C., Schoenberger J.M., Rogler C.E., and Chisari F.V., J Virol 70, 7056-7061, 1996.

    PubMed  Google Scholar 

  85. Miska S. and Will H., Arch Virol Suppl 8, 155-169, 1993.

    Google Scholar 

  86. Carman W.F., Intervirology 38, 75-88, 1995.

    PubMed  Google Scholar 

  87. Gunther S., Piwon N., Iwanska A., Schilling R., Meisel H., and Will H., J Virol 70, 8318-8331, 1996.

    PubMed  Google Scholar 

  88. Baumert T.F., Rogers S.A., Hasegawa K., and Liang T.J., J Clin Invest 98, 2268-2276, 1996.

    PubMed  Google Scholar 

  89. Okamoto H., Tsuda F., Akahane Y., Sugai Y., Yoshiba M., Moriyama K., Tanaka T., Miyakawa Y., and Mayumi M., J Virol 68, 8102-8110, 1994.

    PubMed  Google Scholar 

  90. Pult I., Chouard T., Wieland S., Klemenz R., Yaniv M., and Blum H.E., Hepatology 25, 1507-1515, 1997.

    PubMed  Google Scholar 

  91. Xu Z. and Yen T.S., J Virol 70, 133-140, 1996.

    PubMed  Google Scholar 

  92. Gerken G., Kremsdorf D., Capel F., Petit M.A., Dauguet C., Manns M.P., Meyer Z.B.K., and Brechot C., Virology 183, 555-565, 1991.

    PubMed  Google Scholar 

  93. Fernholz D., Galle P.R., Stemler M., Brunetto M., Bonino F., and Will H., Virology 194, 137-148, 1993.

    PubMed  Google Scholar 

  94. Bock C.T., Tillmann H.L., Maschek H.J., Manns M.P. and Trautwein C., Gastroenterology 113, 1976-1982, 1997.

    PubMed  Google Scholar 

  95. Tipples G.A., Ma M.M., Fischer K.P., Bain V.G., Kneteman N.M., and Tyrrell D.L., Hepatology 24, 714-717, 1996.

    PubMed  Google Scholar 

  96. Ling R., Mutimer D., Ahmed M., Boxall E.H., Elias E., Dusheiko G.M., and Harrison T.J., Hepatology 24, 711-713, 1996.

    PubMed  Google Scholar 

  97. Bartholomew M.M., Jansen R.W., Jeffers L.J., Reddy K.R., Johnson L.C., Bunzendahl H., Condreay L.D., Tzakis A.G., Schiff E.R., and Brown N.A., Lancet 349, 20-22, 1997.

    PubMed  Google Scholar 

  98. Aye T.T., Bartholomeusz A., Shaw T., Bowden S., Breschkin A., McMillan J., Angus P., and Locarnini S., J Hepatol 26, 1148-1153, 1997.

    PubMed  Google Scholar 

  99. Melegari M., Scaglioni P.P., and Wands J.R., Hepatology 27, 628-633, 1998.

    PubMed  Google Scholar 

  100. Protzer-Knolle U. and Gerken G., Biotest Biomedical Bulletin 5, 297-299, 1997.

    Google Scholar 

  101. Carman W.F., J Viral Hepat 1, 11-20, 1997.

    Google Scholar 

  102. Carman W., Zanetti A.R., Karayiannis P., Waters J., Manzillo G., Tanzi E., Zuckerman A.J., and Thomas H.C., Lancet 336, 325-329, 1990.

    PubMed  Google Scholar 

  103. Waters J.A., Kennedy M., Voet P., Hauser P., Petre J., Carman W. and Thomas H.C., J Clin Invest 90, 2543-2547, 1992.

    PubMed  Google Scholar 

  104. McMahon G., Ehrlich P.H., Moustafa Z.A., McCarthy L.A., Dottavio D., Tolpin M.D., Nadler P.I. and Östberg., Hepatology 15, 757-766, 1992.

    PubMed  Google Scholar 

  105. Protzer-Knolle U., Naumann U., Bartenschlager R., Berg T., Hopf U., Meyer zum Büschenfelde K.H., Neuhaus P., and Gerken G., Hepatology 27, 254-263, 1998.

    PubMed  Google Scholar 

  106. Ghany M.G., Ayola B., Villamil F.G., Gish R.G., Rojter S., Vierling J.M. and Lok A.S., Hepatology 27, 213-222, 1998.

    PubMed  Google Scholar 

  107. Carman W.F., Trautwein C., van Deursen F.J., Colman K., Dornan E., McIntyre G., Waters J., Kliem V., Muller R., Thomas H.C. and Manns M.P., Hepatology 24, 489-493, 1996.

    PubMed  Google Scholar 

  108. Guidotti L.G., Rochford R., Chung I., Shapiro M., Purcell R., and Chisari F., Viral Clearance Without Destruction of Infected Cells During Acute HBV Infection. Science 284, 825-829, 1999.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Protzer, U., Schaller, H. Immune Escape by Hepatitis B Viruses. Virus Genes 21, 27–37 (2000). https://doi.org/10.1023/A:1008128212380

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1008128212380

Navigation