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CD8 epitope escape and reversion in acute HCV infection

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CD8 epitope escape and reversion in acute HCV infection. / Timm, Joerg; Lauer, Georg M; Kavanagh, Daniel G; Sheridan, Isabelle; Kim, Arthur Y; Lucas, Michaela; Pillay, Thillagavathie; Ouchi, Kei; Reyor, Laura L; Schulze zur Wiesch, Julian; Gandhi, Rajesh T; Chung, Raymond T; Bhardwaj, Nina; Klenerman, Paul; Walker, Bruce D; Allen, Todd M.

in: J EXP MED, Jahrgang 200, Nr. 12, 20.12.2004, S. 1593-1604.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Timm, J, Lauer, GM, Kavanagh, DG, Sheridan, I, Kim, AY, Lucas, M, Pillay, T, Ouchi, K, Reyor, LL, Schulze zur Wiesch, J, Gandhi, RT, Chung, RT, Bhardwaj, N, Klenerman, P, Walker, BD & Allen, TM 2004, 'CD8 epitope escape and reversion in acute HCV infection', J EXP MED, Jg. 200, Nr. 12, S. 1593-1604. https://doi.org/10.1084/jem.20041006

APA

Timm, J., Lauer, G. M., Kavanagh, D. G., Sheridan, I., Kim, A. Y., Lucas, M., Pillay, T., Ouchi, K., Reyor, L. L., Schulze zur Wiesch, J., Gandhi, R. T., Chung, R. T., Bhardwaj, N., Klenerman, P., Walker, B. D., & Allen, T. M. (2004). CD8 epitope escape and reversion in acute HCV infection. J EXP MED, 200(12), 1593-1604. https://doi.org/10.1084/jem.20041006

Vancouver

Timm J, Lauer GM, Kavanagh DG, Sheridan I, Kim AY, Lucas M et al. CD8 epitope escape and reversion in acute HCV infection. J EXP MED. 2004 Dez 20;200(12):1593-1604. https://doi.org/10.1084/jem.20041006

Bibtex

@article{96d6eafa89744ad19b935e77711b3ad7,
title = "CD8 epitope escape and reversion in acute HCV infection",
abstract = "In the setting of acute hepatitis C virus (HCV) infection, robust HCV-specific CD8+ cytotoxic T lymphocyte (CTL) responses are associated with initial control of viremia. Despite these responses, 70-80% of individuals develop persistent infection. Although viral escape from CD8 responses has been illustrated in the chimpanzee model of HCV infection, the effect of CD8 selection pressure on viral evolution and containment in acute HCV infection in humans remains unclear. Here, we examined viral evolution in an immunodominant human histocompatibility leukocyte antigen (HLA)-B8-restricted NS3 epitope in subjects with acute HCV infection. Development of mutations within the epitope coincided with loss of strong ex vivo tetramer and interferon gamma enzyme-linked immunospot responses, and endogenous expression of variant NS3 sequences suggested that the selected mutations altered processing and presentation of the variant epitope. Analysis of NS3 sequences from 30 additional chronic HCV-infected subjects revealed a strong association between sequence variation within this region and expression of HLA-B8, supporting reproducible allele-specific selection pressures at the population level. Interestingly, transmission of an HLA-B8-associated escape mutation to an HLA-B8 negative subject resulted in rapid reversion of the mutation. Together, these data indicate that viral escape from CD8+ T cell responses occurs during human HCV infection and that acute immune selection pressure is of sufficient magnitude to influence HCV evolution.",
keywords = "Acute Disease, Amino Acid Sequence/genetics, Amino Acid Substitution/genetics, Animals, CD8-Positive T-Lymphocytes/immunology, Chronic Disease, Epitopes, T-Lymphocyte/immunology, Evolution, Molecular, Female, Genetic Variation/genetics, HLA-B8 Antigen/immunology, Hepacivirus/genetics, Hepatitis C/genetics, Humans, Lymphocyte Activation/immunology, Male, Molecular Sequence Data, Mutation/genetics, Viral Nonstructural Proteins/genetics, Viremia/immunology",
author = "Joerg Timm and Lauer, {Georg M} and Kavanagh, {Daniel G} and Isabelle Sheridan and Kim, {Arthur Y} and Michaela Lucas and Thillagavathie Pillay and Kei Ouchi and Reyor, {Laura L} and {Schulze zur Wiesch}, Julian and Gandhi, {Rajesh T} and Chung, {Raymond T} and Nina Bhardwaj and Paul Klenerman and Walker, {Bruce D} and Allen, {Todd M}",
year = "2004",
month = dec,
day = "20",
doi = "10.1084/jem.20041006",
language = "English",
volume = "200",
pages = "1593--1604",
journal = "J EXP MED",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "12",

}

RIS

TY - JOUR

T1 - CD8 epitope escape and reversion in acute HCV infection

AU - Timm, Joerg

AU - Lauer, Georg M

AU - Kavanagh, Daniel G

AU - Sheridan, Isabelle

AU - Kim, Arthur Y

AU - Lucas, Michaela

AU - Pillay, Thillagavathie

AU - Ouchi, Kei

AU - Reyor, Laura L

AU - Schulze zur Wiesch, Julian

AU - Gandhi, Rajesh T

AU - Chung, Raymond T

AU - Bhardwaj, Nina

AU - Klenerman, Paul

AU - Walker, Bruce D

AU - Allen, Todd M

PY - 2004/12/20

Y1 - 2004/12/20

N2 - In the setting of acute hepatitis C virus (HCV) infection, robust HCV-specific CD8+ cytotoxic T lymphocyte (CTL) responses are associated with initial control of viremia. Despite these responses, 70-80% of individuals develop persistent infection. Although viral escape from CD8 responses has been illustrated in the chimpanzee model of HCV infection, the effect of CD8 selection pressure on viral evolution and containment in acute HCV infection in humans remains unclear. Here, we examined viral evolution in an immunodominant human histocompatibility leukocyte antigen (HLA)-B8-restricted NS3 epitope in subjects with acute HCV infection. Development of mutations within the epitope coincided with loss of strong ex vivo tetramer and interferon gamma enzyme-linked immunospot responses, and endogenous expression of variant NS3 sequences suggested that the selected mutations altered processing and presentation of the variant epitope. Analysis of NS3 sequences from 30 additional chronic HCV-infected subjects revealed a strong association between sequence variation within this region and expression of HLA-B8, supporting reproducible allele-specific selection pressures at the population level. Interestingly, transmission of an HLA-B8-associated escape mutation to an HLA-B8 negative subject resulted in rapid reversion of the mutation. Together, these data indicate that viral escape from CD8+ T cell responses occurs during human HCV infection and that acute immune selection pressure is of sufficient magnitude to influence HCV evolution.

AB - In the setting of acute hepatitis C virus (HCV) infection, robust HCV-specific CD8+ cytotoxic T lymphocyte (CTL) responses are associated with initial control of viremia. Despite these responses, 70-80% of individuals develop persistent infection. Although viral escape from CD8 responses has been illustrated in the chimpanzee model of HCV infection, the effect of CD8 selection pressure on viral evolution and containment in acute HCV infection in humans remains unclear. Here, we examined viral evolution in an immunodominant human histocompatibility leukocyte antigen (HLA)-B8-restricted NS3 epitope in subjects with acute HCV infection. Development of mutations within the epitope coincided with loss of strong ex vivo tetramer and interferon gamma enzyme-linked immunospot responses, and endogenous expression of variant NS3 sequences suggested that the selected mutations altered processing and presentation of the variant epitope. Analysis of NS3 sequences from 30 additional chronic HCV-infected subjects revealed a strong association between sequence variation within this region and expression of HLA-B8, supporting reproducible allele-specific selection pressures at the population level. Interestingly, transmission of an HLA-B8-associated escape mutation to an HLA-B8 negative subject resulted in rapid reversion of the mutation. Together, these data indicate that viral escape from CD8+ T cell responses occurs during human HCV infection and that acute immune selection pressure is of sufficient magnitude to influence HCV evolution.

KW - Acute Disease

KW - Amino Acid Sequence/genetics

KW - Amino Acid Substitution/genetics

KW - Animals

KW - CD8-Positive T-Lymphocytes/immunology

KW - Chronic Disease

KW - Epitopes, T-Lymphocyte/immunology

KW - Evolution, Molecular

KW - Female

KW - Genetic Variation/genetics

KW - HLA-B8 Antigen/immunology

KW - Hepacivirus/genetics

KW - Hepatitis C/genetics

KW - Humans

KW - Lymphocyte Activation/immunology

KW - Male

KW - Molecular Sequence Data

KW - Mutation/genetics

KW - Viral Nonstructural Proteins/genetics

KW - Viremia/immunology

U2 - 10.1084/jem.20041006

DO - 10.1084/jem.20041006

M3 - SCORING: Journal article

C2 - 15611288

VL - 200

SP - 1593

EP - 1604

JO - J EXP MED

JF - J EXP MED

SN - 0022-1007

IS - 12

ER -