Differential virus-specific CD8T-cell epitope repertoire in hepatitis C virus genotype 1 versus 4

TY - JOUR

T1 - Differential virus-specific CD8T-cell epitope repertoire in hepatitis C virus genotype 1 versus 4

AU - Luxenburger, Hendrik

AU - Graß, Franziska

AU - Baermann, Janina

AU - Boettler, Tobias

AU - Marget, Matthias

AU - Emmerich, Florian

AU - Panning, Marcus

AU - Thimme, Robert

AU - Nitschke, Katja

AU - Neumann-Haefelin, Christoph

N1 - This article is protected by copyright. All rights reserved.

PY - 2018/7

Y1 - 2018/7

N2 - Virus-specific CD8+ T-cell responses play an important role in the outcome of hepatitis C virus (HCV) infection. To date, most HCV-specific CD8+ T-cell epitopes have been defined in HCV genotype 1 infection. In contrast, the HCV genotype 4-specific CD8+ T-cell response is poorly defined. Here, we analysed whether known HCV-specific CD8+ T-cell epitopes are also recognized in HCV genotype 4-infected patients and set out to identify the first HCV genotype 4-specific CD8+ T-cell epitopes. We studied patients chronically infected with HCV genotype 1 (n = 20) or 4 (n = 21) using 91 well-described HCV-specific epitope peptides. In addition, we analysed 24 genotype 4-infected patients using 40 epitope candidates predicted using an in silico approach. HCV-specific CD8+ T-cell responses targeting previously described epitopes were detectable in the majority of genotype 1-infected patients (11 of 20). In contrast, patients infected with HCV genotype 4 rarely targeted these epitopes (4 of 21; P = .0247). Importantly, we were able to identify eight novel HCV genotype 4-specific CD8+ T-cell epitopes. Only one of these epitopes was shared between genotype 1 and genotype 4. These results indicate that there is little overlap between CD8+ T-cell repertoires targeting HCV genotype 1 and 4. Prophylactic vaccination studies based on HCV genotype 1 are currently underway. However, in countries with the highest prevalence of HCV infection, such as Egypt, most patients are infected with HCV genotype 4. Thus, prophylactic vaccination strategies need to be adapted to HCV genotype 4 before their application to regions where HCV genotype 4 is endemic.

AB - Virus-specific CD8+ T-cell responses play an important role in the outcome of hepatitis C virus (HCV) infection. To date, most HCV-specific CD8+ T-cell epitopes have been defined in HCV genotype 1 infection. In contrast, the HCV genotype 4-specific CD8+ T-cell response is poorly defined. Here, we analysed whether known HCV-specific CD8+ T-cell epitopes are also recognized in HCV genotype 4-infected patients and set out to identify the first HCV genotype 4-specific CD8+ T-cell epitopes. We studied patients chronically infected with HCV genotype 1 (n = 20) or 4 (n = 21) using 91 well-described HCV-specific epitope peptides. In addition, we analysed 24 genotype 4-infected patients using 40 epitope candidates predicted using an in silico approach. HCV-specific CD8+ T-cell responses targeting previously described epitopes were detectable in the majority of genotype 1-infected patients (11 of 20). In contrast, patients infected with HCV genotype 4 rarely targeted these epitopes (4 of 21; P = .0247). Importantly, we were able to identify eight novel HCV genotype 4-specific CD8+ T-cell epitopes. Only one of these epitopes was shared between genotype 1 and genotype 4. These results indicate that there is little overlap between CD8+ T-cell repertoires targeting HCV genotype 1 and 4. Prophylactic vaccination studies based on HCV genotype 1 are currently underway. However, in countries with the highest prevalence of HCV infection, such as Egypt, most patients are infected with HCV genotype 4. Thus, prophylactic vaccination strategies need to be adapted to HCV genotype 4 before their application to regions where HCV genotype 4 is endemic.

KW - Journal Article

U2 - 10.1111/jvh.12874

DO - 10.1111/jvh.12874

M3 - SCORING: Journal article

C2 - 29397015

VL - 25

SP - 779

EP - 790

JO - J VIRAL HEPATITIS

JF - J VIRAL HEPATITIS

SN - 1352-0504

IS - 7

ER -