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Erschienen in: Indian Journal of Gastroenterology 4/2017

25.07.2017 | Original Article

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

verfasst von: Sareh Zhand, Alijan Tabarraei, Amineh Nazari, Abdolvahab Moradi

Erschienen in: Indian Journal of Gastroenterology | Ausgabe 4/2017

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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.
Literatur
1.
Zurück zum Zitat Ganem D, Schneider RJ. Hepadnaviridae: the viruses and their replication. Fields Virol. 2001;2:2923–69. Ganem D, Schneider RJ. Hepadnaviridae: the viruses and their replication. Fields Virol. 2001;2:2923–69.
2.
Zurück zum Zitat 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. 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.
3.
4.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
5.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
6.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
9.
Zurück zum Zitat 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. 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.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Hunt CM, McGill JM, Allen MI, Condreay LD. Clinical relevance of hepatitis B viral mutations. Hepatology. 2000;31:1037–44.CrossRefPubMed Hunt CM, McGill JM, Allen MI, Condreay LD. Clinical relevance of hepatitis B viral mutations. Hepatology. 2000;31:1037–44.CrossRefPubMed
12.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
13.
Zurück zum Zitat 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 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
14.
Zurück zum Zitat Alavian SM, Fallahian F, Lankarani KB. The changing epidemiology of viral hepatitis B in Iran. J Gastrointestin Liver Dis. 2007;16:403–6.PubMed Alavian SM, Fallahian F, Lankarani KB. The changing epidemiology of viral hepatitis B in Iran. J Gastrointestin Liver Dis. 2007;16:403–6.PubMed
15.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
16.
17.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
20.
Zurück zum Zitat 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. 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.
21.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
23.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
Metadaten
Titel
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
verfasst von
Sareh Zhand
Alijan Tabarraei
Amineh Nazari
Abdolvahab Moradi
Publikationsdatum
25.07.2017
Verlag
Springer India
Erschienen in
Indian Journal of Gastroenterology / Ausgabe 4/2017
Print ISSN: 0254-8860
Elektronische ISSN: 0975-0711
DOI
https://doi.org/10.1007/s12664-017-0767-z

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