Skip to main content

Advertisement

SpringerLink
Log in

Cytotoxic T lymphocytes and CD4 epitope mutations in the pre-core/core region of hepatitis B virus in chronic hepatitis B carriers in Northeast Iran

  • Original Article
  • Published:
Indian Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Backgrounds

Hepatitis B virus (HBV) is vulnerable to many various mutations. Those within epitopes recognized by sensitized T cells may influence the re-emergence of the virus. This study was designed to investigate the mutation in immune epitope regions of HBV pre-core/core among chronic HBV patients of Golestan province, Northeast Iran.

Methods

In 120 chronic HBV carriers, HBV DNA was extracted from blood plasma samples and PCR was done using specific primers. Direct sequencing and alignment of the pre-core/core region were applied using reference sequence from Gene Bank database (Accession Number AB033559).

Results

The study showed 27 inferred amino acid substitutions, 9 of which (33.3%) were in CD4 and 2 (7.4%) in cytotoxic T lymphocytes’ (CTL) epitopes and 16 other mutations (59.2%) were observed in other regions.

Conclusions

CTL escape mutations were not commonly observed in pre-core/core sequences of chronic HBV carriers in the locale of study. It can be concluded that most of the inferred amino acid substitutions occur in different immune epitopes other than CTL and CD4.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Ganem D, Schneider RJ. Hepadnaviridae: the viruses and their replication. Fields Virol. 2001;2:2923–69.

    Google Scholar 

  2. Alexopoulou A. Mutants in the precore, core promoter, and core regions of hepatitis B virus, and their clinical relevance. Ann Gastroenterol. 2009;22:13–23.

    Google Scholar 

  3. Jung MC, Pape GR. Immunology of hepatitis B infection. Lancet Infect Dis. 2002;2:43–50.

    Article  CAS  PubMed  Google Scholar 

  4. Penna A, Del Prete G, Cavalli A, et al. Predominant T-helper 1 cytokine profile of hepatitis B virus nucleocapsid-specific T cells in acute self-limited hepatitis B. Hepatology. 1997;25:1022–7.

    Article  CAS  PubMed  Google Scholar 

  5. Sobao Y, Tomiyama H, Sugi K, et al. The role of hepatitis B virus-specific memory CD8 T cells in the control of viral replication. J Hepatol. 2002;36:105–15.

    Article  PubMed  Google Scholar 

  6. Webster GJ, Reignat S, Brown D, et al. Longitudinal analysis of CD8+ T cells specific for structural and nonstructural hepatitis B virus proteins in patients with chronic hepatitis B: implications for immunotherapy. J Virol. 2004;78:5707–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Chang JJ, Wightman F, Bartholomeusz A, et al. Reduced hepatitis B virus (HBV)-specific CD4+ T-cell responses in human immunodeficiency virus type 1-HBV-coinfected individuals receiving HBV-active antiretroviral therapy. J Virol. 2005;79:3038–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Urbani S, Boni C, Amadei B, et al. Acute phase HBV-specific T cell responses associated with HBV persistence after HBV/HCV coinfection. Hepatology. 2005;41:826–31.

    Article  PubMed  Google Scholar 

  9. Locarnini S, Eds. Virology of Hepatitis B Virus. Molecular. Seminars in liver Disease. Copyright© 2004 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. 2004.

  10. Kakimi K, Isogawa M, Chung J, Sette A, Chisari FV. Immunogenicity and tolerogenicity of hepatitis B virus structural and nonstructural proteins: implications for immunotherapy of persistent viral infections. J Virol. 2002;76:8609–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Hunt CM, McGill JM, Allen MI, Condreay LD. Clinical relevance of hepatitis B viral mutations. Hepatology. 2000;31:1037–44.

    Article  CAS  PubMed  Google Scholar 

  12. Gholamreza R, Shahryar S, Abbasali K, et al. Seroprevalence of hepatitis B virus and its co-infection with hepatitis D virus and hepatitis C virus in Iranian adult population. Indian J Med Sci. 2007;61:263–8.

    Article  PubMed  Google Scholar 

  13. Merat S, Rezvan H, Nouraie M, et al. The prevalence of hepatitis B surface antigen and anti-hepatitis B core antibody in Iran: a population-based study. Arch Iran Med. 2009;12:225–31.

    PubMed  Google Scholar 

  14. Alavian SM, Fallahian F, Lankarani KB. The changing epidemiology of viral hepatitis B in Iran. J Gastrointestin Liver Dis. 2007;16:403–6.

    PubMed  Google Scholar 

  15. Alghamdi A, Aref N, El-Hazmi M, et al. Correlation between hepatitis B surface antigen titers and HBV DNA levels. Saudi J Gastroenterol. 2013;19:252–7.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Mohamadkhani A, Jazii FR, Poustchi H, et al. The role of mutations in core protein of hepatitis B virus in liver fibrosis. Virol J. 2009;6:209.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Park YM, Kim BS, Tabor E. Precore codon 28 stop mutation in hepatitis B virus from patients with hepatocellular carcinoma. Korean J Intern Med. 1997;12:201–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Loggi E, Bihl FK, Cursaro C, et al. Virus-specific immune response in HBeAg-negative chronic hepatitis B: relationship with clinical profile and HBsAg serum levels. PLoS One. 2013;8:e65327.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kim D, Lyoo KS, Smith D, et al. Number of mutations within CTL-defined epitopes of the hepatitis B virus (HBV) core region is associated with HBV disease progression. J Med Virol. 2011;83:2082–7.

    Article  CAS  PubMed  Google Scholar 

  20. Gu XB, Yang XJ, Wang D, Hua Z, Xu YQ, Lu ZH. Relationship between serum HBV DNA level and HBV-specific, nonspecific cytotoxic T lymphocytes and natural killer cells in patients with chronic hepatitis B. Chin Med J (Engl). 2009;122:2129–32.

    CAS  Google Scholar 

  21. Cheng CP, Lee PF, Liu WC, et al. Analysis of precore/core covariances associated with viral kinetics and genotypes in hepatitis B e antigen-positive chronic hepatitis B patients. PLoS One. 2012;7:e32553.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Alexopoulou A, Baltayiannis G, Eroglu C, et al. Core mutations in patients with acute episodes of chronic HBV infection are associated with the emergence of new immune recognition sites and the development of high IgM anti-HBc index values. J Med Virol. 2009;81:34–41.

    Article  PubMed  Google Scholar 

  23. Sun L, Zhang Y, Zhao B, et al. A new unconventional HLA-A2-restricted epitope from HBV core protein elicits antiviral cytotoxic T lymphocytes. Protein Cell. 2014;5:317–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Moradi A, Zhand S, Ghaemi A, Javid N, Tabarraei A. Mutations in the S gene region of hepatitis B virus genotype D in Golestan Province-Iran. Virus Genes. 2012;44:382–7.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was performed with financial support from the Research Deputy, Golestan University of Medical Sciences.

Author information

Authors and Affiliations

  1. Department of Microbiology, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran

    Sareh Zhand, Alijan Tabarraei & Abdolvahab Moradi

  2. Tehran University of Medical Sciences, Tehran, Iran

    Amineh Nazari

Authors
  1. Sareh Zhand
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alijan Tabarraei
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Amineh Nazari
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Abdolvahab Moradi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Abdolvahab Moradi.

Ethics declarations

Conflict of interest

SZ, AT, AN, and AM declare that they have no conflict of interest.

Ethics statement

The authors declare that the study was performed in accordance with the Helsinki declaration of 1975, as revised in 2000 and 2008 concerning human and animal rights, and the authors followed the policy concerning informed consent as shown on springer.com.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhand, S., Tabarraei, A., Nazari, A. et al. Cytotoxic T lymphocytes and CD4 epitope mutations in the pre-core/core region of hepatitis B virus in chronic hepatitis B carriers in Northeast Iran. Indian J Gastroenterol 36, 253–257 (2017). https://doi.org/10.1007/s12664-017-0767-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12664-017-0767-z

Keywords

Search

Navigation