Display options
Cite
Mason WS, Litwin S, Jilbert AR. Immune selection during chronic hepadnavirus infection. Hepatol Int. 2007;2(1):3-16doi: 10.1007/s12072-007-9024-3.
Mason, W. S., Litwin, S., & Jilbert, A. R. (2008). Immune selection during chronic hepadnavirus infection. Hepatology international, 2(1), 3-16. https://doi.org/10.1007/s12072-007-9024-3
Mason, William S, et al. "Immune selection during chronic hepadnavirus infection." Hepatology international vol. 2,1 (2008): 3-16. doi: https://doi.org/10.1007/s12072-007-9024-3
Mason WS, Litwin S, Jilbert AR. Immune selection during chronic hepadnavirus infection. Hepatol Int. 2008 Mar;2(1):3-16. doi: 10.1007/s12072-007-9024-3. Epub 2007 Dec 14. PMID: 19669275; PMCID: PMC2716866.
Copy Download .nbib Format: NLM
Share it on

Hepatol Int. 2008 Mar;2(1):3-16. doi: 10.1007/s12072-007-9024-3. Epub 2007 Dec 14.

Immune selection during chronic hepadnavirus infection.

Hepatology international

William S Mason, Sam Litwin, Allison R Jilbert

Affiliations

  1. Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111, USA, [email protected].

PMID: 19669275 PMCID: PMC2716866 DOI: 10.1007/s12072-007-9024-3

Abstract

PURPOSE: Late-stage outcomes of chronic hepatitis B virus (HBV) infection, including fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) result from persistent liver injury mediated by HBV antigen specific cytotoxic T lymphocytes (CTLs). Two other outcomes that often accompany chronic infection, the emergence of mutant viruses, including HBe-antigen negative (HBeAg (-)) HBV, and a reduction over time in the fraction of hepatocytes productively infected with HBV, may also result from persistent immune attack by antiviral CTLs. To gain insights into how these latter changes take place, we employed computer simulations of the chronically infected liver.

METHODS: Computational programs were used to model the emergence of both virus-free hepatocytes and mutant strains of HBV.

RESULTS: The computer modeling predicted that if cell-to-cell spread of virus is an efficient process during chronic infections, an HBV mutant that replicated significantly more efficiently than the wild type would emerge as the prevalent virus in a few years, much more rapidly than observed, while a mutant that replicated with the same or lower efficiency would fail to emerge. Thus, either cell-to-cell spread is inefficient or mutants do not replicate appreciably more efficiently than wild type. In contrast, with immune selection and a higher rate of killing of hepatocytes infected with wild-type virus, emergence of mutant virus can be explained without the need for a higher replication rate. Immune selection could also explain the emergence of virus-free hepatocytes that are unable to support HBV infection, since they should have a lower turnover rate than infected hepatocytes.

References

  1. Intervirology. 1985;24(4):220-5 - PubMed
  2. Proc Natl Acad Sci U S A. 2005 Dec 6;102(49):17780-5 - PubMed
  3. Virology. 1983 Dec;131(2):375-84 - PubMed
  4. J Virol. 1999 May;73(5):3616-22 - PubMed
  5. Hepatology. 1999 Feb;29(2):563-71 - PubMed
  6. World J Gastroenterol. 2007 Jan 7;13(1):39-47 - PubMed
  7. J Virol. 1989 Dec;63(12):5238-43 - PubMed
  8. Gastroenterology. 1976 Sep;71(3):462-9 - PubMed
  9. Hepatology. 1997 Dec;26(6):1607-15 - PubMed
  10. J Natl Cancer Inst. 1982 Sep;69(3):565-8 - PubMed
  11. J Virol. 1995 Jul;69(7):4029-36 - PubMed
  12. Cancer Res. 1993 May 1;53(9):2020-7 - PubMed
  13. J Cell Biol. 1988 Apr;106(4):1093-104 - PubMed
  14. J Clin Invest. 1995 Sep;96(3):1527-34 - PubMed
  15. Gastroenterology. 1987 Jan;92(1):192-6 - PubMed
  16. J Virol. 2000 Jun;74(11):5257-65 - PubMed
  17. Virology. 2007 Mar 15;359(2):283-94 - PubMed
  18. J Clin Pathol. 1985 Apr;38(4):393-8 - PubMed
  19. Virology. 1986 Jul 30;152(2):477-82 - PubMed
  20. Proc Natl Acad Sci U S A. 2004 Oct 12;101(41):14913-8 - PubMed
  21. J Virol. 2001 Jan;75(1):311-22 - PubMed
  22. Semin Liver Dis. 2006 May;26(2):116-29 - PubMed
  23. J Med Virol. 2006 Jul;78(7):906-10 - PubMed
  24. J Virol. 1999 Feb;73(2):1492-502 - PubMed
  25. Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12372-7 - PubMed
  26. J Virol. 1999 Dec;73(12):9710-7 - PubMed
  27. Hepatology. 2000 Jul;32(1):139-46 - PubMed
  28. Hepatology. 1995 Jul;22(1):160-8 - PubMed
  29. Toxicol Pathol. 2003 Jan-Feb;31(1):134-9 - PubMed
  30. Gastroenterology. 1977 Oct;73(4 Pt 1):664-7 - PubMed
  31. J Clin Microbiol. 1997 Jan;35(1):102-5 - PubMed
  32. Proc Natl Acad Sci U S A. 2005 Jan 25;102(4):1139-44 - PubMed
  33. Am J Epidemiol. 1977 Feb;105(2):94-8 - PubMed
  34. J Hepatol. 2000 Oct;33(4):580-600 - PubMed
  35. J Virol. 1991 Mar;65(3):1310-7 - PubMed
  36. J Virol. 1995 Dec;69(12):8102-8 - PubMed
  37. Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11652-9 - PubMed
  38. Methods Mol Med. 2004;95:213-26 - PubMed
  39. J Hepatol. 2002 Oct;37(4):478-85 - PubMed
  40. Virology. 1998 Nov 10;251(1):85-95 - PubMed
  41. J Virol. 2001 Oct;75(20):9623-32 - PubMed
  42. Int J Cancer. 1977 Nov 15;20(5):643-54 - PubMed
  43. Cancer. 1985 Jul 15;56(2):321-7 - PubMed
  44. Proc Natl Acad Sci U S A. 1999 Sep 14;96(19):10818-23 - PubMed
  45. J Virol. 1992 Sep;66(9):5682-4 - PubMed
  46. J Virol. 1996 Mar;70(3):2000-7 - PubMed
  47. Proc Natl Acad Sci U S A. 2004 Jul 27;101(30):11135-40 - PubMed
  48. Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):2129-34 - PubMed
  49. Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4398-402 - PubMed
  50. Gastroenterology. 1976 Jul;71(1):102-8 - PubMed
  51. Cancer. 1988 Sep 1;62(5):915-21 - PubMed
  52. Semin Liver Dis. 2006 May;26(2):130-41 - PubMed
  53. J Virol. 1994 Sep;68(9):5792-803 - PubMed
  54. Arch Pathol Lab Med. 1990 Oct;114(10):1042-5 - PubMed
  55. J Virol. 1992 Mar;66(3):1377-88 - PubMed
  56. J Virol. 1998 Nov;72(11):8710-7 - PubMed
  57. J Virol. 1987 Dec;61(12):3701-9 - PubMed
  58. J Clin Virol. 2005 Dec;34 Suppl 1:S96-S107 - PubMed
  59. Cancer Epidemiol Biomarkers Prev. 1998 Jul;7(7):559-65 - PubMed
  60. J Virol. 1995 Jun;69(6):3350-7 - PubMed

Publication Types