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Susceptibility to chronic hepatitis C virus infection is influenced by sequence differences in immunodominant CD8+ T cell epitopes

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Susceptibility to chronic hepatitis C virus infection is influenced by sequence differences in immunodominant CD8+ T cell epitopes. / Ziegler, Susanne; Ruhl, Marianne; Tenckhoff, Hannelore; Wiese, Manfred; Heinemann, Falko M; Horn, Peter A; Spengler, Ulrich; Neumann-Haefelin, Christoph; Nattermann, Jacob; Timm, Jörg; East-German HCV Study Group.

In: J HEPATOL, Vol. 58, No. 1, 01.2013, p. 24-30.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Ziegler, S, Ruhl, M, Tenckhoff, H, Wiese, M, Heinemann, FM, Horn, PA, Spengler, U, Neumann-Haefelin, C, Nattermann, J, Timm, J & East-German HCV Study Group 2013, 'Susceptibility to chronic hepatitis C virus infection is influenced by sequence differences in immunodominant CD8+ T cell epitopes', J HEPATOL, vol. 58, no. 1, pp. 24-30. https://doi.org/10.1016/j.jhep.2012.08.016

APA

Ziegler, S., Ruhl, M., Tenckhoff, H., Wiese, M., Heinemann, F. M., Horn, P. A., Spengler, U., Neumann-Haefelin, C., Nattermann, J., Timm, J., & East-German HCV Study Group (2013). Susceptibility to chronic hepatitis C virus infection is influenced by sequence differences in immunodominant CD8+ T cell epitopes. J HEPATOL, 58(1), 24-30. https://doi.org/10.1016/j.jhep.2012.08.016

Vancouver

Ziegler S, Ruhl M, Tenckhoff H, Wiese M, Heinemann FM, Horn PA et al. Susceptibility to chronic hepatitis C virus infection is influenced by sequence differences in immunodominant CD8+ T cell epitopes. J HEPATOL. 2013 Jan;58(1):24-30. https://doi.org/10.1016/j.jhep.2012.08.016

Bibtex

@article{c1ead5a2f8ae4f118082d19e263deb51,
title = "Susceptibility to chronic hepatitis C virus infection is influenced by sequence differences in immunodominant CD8+ T cell epitopes",
abstract = "BACKGROUND & AIMS: The antiviral immune response against HCV by CD8+ T cells plays a central role in viral containment. In a large HCV genotype 1b outbreak in Ireland, HLA-B(∗)08 was identified as a risk allele for chronic infection and HLA-A(∗)03 and HLA-B(∗)27 were associated with higher clearance rates. Here we took advantage of a similar large common source HCV genotype 1b outbreak (East-German cohort) to determine the role of HLA class I alleles and the sequence of the infection source, in immunodominant CD8+ T cell epitopes for disease outcome.METHODS: HLA-type and IL28B genotype were determined in 216 patients with chronic and 95 with spontaneously resolved HCV infection. The viral sequence in immunodominant epitopes was determined in the infection source and in patients with chronic infection.RESULTS: In contrast to the Irish cohort, HLA-B(∗)08, HLA-A(∗)03 and HLA-B(∗)27 were neutral for disease outcome even when the cohort was stratified for the IL28B genotype. Sequence analysis of the immunodominant epitopes revealed that pre-existing substitutions in the infection source of both cohorts influenced the impact of the corresponding HLA-allele. The immunodominant epitopes presented by the {"}protective{"} alleles HLA-A(∗)03 and -B(∗)27 in the Irish cohort contained substitutions in the source virus of the East-German outbreak. Importantly, the pre-existing substitutions altered subsequent selection pressure and viral evolution in the East-German cohort.CONCLUSIONS: This study highlights that subtle sequence differences in the infection source may have profound effects on the ability to clear HCV infection in the presence of particular HLA class I alleles.",
keywords = "CD8-Positive T-Lymphocytes/immunology, Disease Outbreaks/statistics & numerical data, Disease Susceptibility/epidemiology, Epitopes, T-Lymphocyte/immunology, Genotype, Germany/epidemiology, HLA-A3 Antigen/genetics, HLA-B Antigens/genetics, HLA-B27 Antigen/genetics, HLA-B8 Antigen/genetics, Hepatitis C, Chronic/epidemiology, Humans, Immunodominant Epitopes/immunology, Ireland/epidemiology, Risk Factors",
author = "Susanne Ziegler and Marianne Ruhl and Hannelore Tenckhoff and Manfred Wiese and Heinemann, {Falko M} and Horn, {Peter A} and Ulrich Spengler and Christoph Neumann-Haefelin and Jacob Nattermann and J{\"o}rg Timm and {East-German HCV Study Group}",
note = "Copyright {\textcopyright} 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.",
year = "2013",
month = jan,
doi = "10.1016/j.jhep.2012.08.016",
language = "English",
volume = "58",
pages = "24--30",
journal = "J HEPATOL",
issn = "0168-8278",
publisher = "Elsevier",
number = "1",

}

RIS

TY - JOUR

T1 - Susceptibility to chronic hepatitis C virus infection is influenced by sequence differences in immunodominant CD8+ T cell epitopes

AU - Ziegler, Susanne

AU - Ruhl, Marianne

AU - Tenckhoff, Hannelore

AU - Wiese, Manfred

AU - Heinemann, Falko M

AU - Horn, Peter A

AU - Spengler, Ulrich

AU - Neumann-Haefelin, Christoph

AU - Nattermann, Jacob

AU - Timm, Jörg

AU - East-German HCV Study Group

N1 - Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

PY - 2013/1

Y1 - 2013/1

N2 - BACKGROUND & AIMS: The antiviral immune response against HCV by CD8+ T cells plays a central role in viral containment. In a large HCV genotype 1b outbreak in Ireland, HLA-B(∗)08 was identified as a risk allele for chronic infection and HLA-A(∗)03 and HLA-B(∗)27 were associated with higher clearance rates. Here we took advantage of a similar large common source HCV genotype 1b outbreak (East-German cohort) to determine the role of HLA class I alleles and the sequence of the infection source, in immunodominant CD8+ T cell epitopes for disease outcome.METHODS: HLA-type and IL28B genotype were determined in 216 patients with chronic and 95 with spontaneously resolved HCV infection. The viral sequence in immunodominant epitopes was determined in the infection source and in patients with chronic infection.RESULTS: In contrast to the Irish cohort, HLA-B(∗)08, HLA-A(∗)03 and HLA-B(∗)27 were neutral for disease outcome even when the cohort was stratified for the IL28B genotype. Sequence analysis of the immunodominant epitopes revealed that pre-existing substitutions in the infection source of both cohorts influenced the impact of the corresponding HLA-allele. The immunodominant epitopes presented by the "protective" alleles HLA-A(∗)03 and -B(∗)27 in the Irish cohort contained substitutions in the source virus of the East-German outbreak. Importantly, the pre-existing substitutions altered subsequent selection pressure and viral evolution in the East-German cohort.CONCLUSIONS: This study highlights that subtle sequence differences in the infection source may have profound effects on the ability to clear HCV infection in the presence of particular HLA class I alleles.

AB - BACKGROUND & AIMS: The antiviral immune response against HCV by CD8+ T cells plays a central role in viral containment. In a large HCV genotype 1b outbreak in Ireland, HLA-B(∗)08 was identified as a risk allele for chronic infection and HLA-A(∗)03 and HLA-B(∗)27 were associated with higher clearance rates. Here we took advantage of a similar large common source HCV genotype 1b outbreak (East-German cohort) to determine the role of HLA class I alleles and the sequence of the infection source, in immunodominant CD8+ T cell epitopes for disease outcome.METHODS: HLA-type and IL28B genotype were determined in 216 patients with chronic and 95 with spontaneously resolved HCV infection. The viral sequence in immunodominant epitopes was determined in the infection source and in patients with chronic infection.RESULTS: In contrast to the Irish cohort, HLA-B(∗)08, HLA-A(∗)03 and HLA-B(∗)27 were neutral for disease outcome even when the cohort was stratified for the IL28B genotype. Sequence analysis of the immunodominant epitopes revealed that pre-existing substitutions in the infection source of both cohorts influenced the impact of the corresponding HLA-allele. The immunodominant epitopes presented by the "protective" alleles HLA-A(∗)03 and -B(∗)27 in the Irish cohort contained substitutions in the source virus of the East-German outbreak. Importantly, the pre-existing substitutions altered subsequent selection pressure and viral evolution in the East-German cohort.CONCLUSIONS: This study highlights that subtle sequence differences in the infection source may have profound effects on the ability to clear HCV infection in the presence of particular HLA class I alleles.

KW - CD8-Positive T-Lymphocytes/immunology

KW - Disease Outbreaks/statistics & numerical data

KW - Disease Susceptibility/epidemiology

KW - Epitopes, T-Lymphocyte/immunology

KW - Genotype

KW - Germany/epidemiology

KW - HLA-A3 Antigen/genetics

KW - HLA-B Antigens/genetics

KW - HLA-B27 Antigen/genetics

KW - HLA-B8 Antigen/genetics

KW - Hepatitis C, Chronic/epidemiology

KW - Humans

KW - Immunodominant Epitopes/immunology

KW - Ireland/epidemiology

KW - Risk Factors

U2 - 10.1016/j.jhep.2012.08.016

DO - 10.1016/j.jhep.2012.08.016

M3 - SCORING: Journal article

C2 - 22925811

VL - 58

SP - 24

EP - 30

JO - J HEPATOL

JF - J HEPATOL

SN - 0168-8278

IS - 1

ER -