Evidence of CD4+ T cell-mediated immune pressure on the Hepatitis C virus genome

Hepatitis C virus (HCV)-specific T cell responses are critical for immune control of infection. Viral adaptation to these responses, via mutations within regions of the virus targeted by CD8+ T cells, is associated with viral persistence. However, identifying viral adaptation to HCV-specific CD4+ T...

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Main Authors: Lucas, M, Deshpande, P, James, I, Rauch, A, Pfafferott, K, Gaylard, E, Merani, S, Plauzolles, A, Lucas, A, McDonnell, W, Kalams, S, Pilkinton, M, Chastain, C, Barnett, L, Prosser, A, Mallal, S, Fitzmaurice, K, Drummer, H, Ansari, M, Pedergnana, V, Barnes, E, John, M, Kelleher, D, Klenerman, P, Gaudieri, S
Formato: Journal article
Idioma:English
Publicado em: Nature Publishing Group 2018
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author Lucas, M
Deshpande, P
James, I
Rauch, A
Pfafferott, K
Gaylard, E
Merani, S
Plauzolles, A
Lucas, A
McDonnell, W
Kalams, S
Pilkinton, M
Chastain, C
Barnett, L
Prosser, A
Mallal, S
Fitzmaurice, K
Drummer, H
Ansari, M
Pedergnana, V
Barnes, E
John, M
Kelleher, D
Klenerman, P
Gaudieri, S
author_facet Lucas, M
Deshpande, P
James, I
Rauch, A
Pfafferott, K
Gaylard, E
Merani, S
Plauzolles, A
Lucas, A
McDonnell, W
Kalams, S
Pilkinton, M
Chastain, C
Barnett, L
Prosser, A
Mallal, S
Fitzmaurice, K
Drummer, H
Ansari, M
Pedergnana, V
Barnes, E
John, M
Kelleher, D
Klenerman, P
Gaudieri, S
author_sort Lucas, M
collection OXFORD
description Hepatitis C virus (HCV)-specific T cell responses are critical for immune control of infection. Viral adaptation to these responses, via mutations within regions of the virus targeted by CD8+ T cells, is associated with viral persistence. However, identifying viral adaptation to HCV-specific CD4+ T cell responses has been difficult although key to understanding anti-HCV immunity. In this context, HCV sequence and host genotype from a single source HCV genotype 1B cohort (n = 63) were analyzed to identify viral changes associated with specific human leucocyte antigen (HLA) class II alleles, as these variable host molecules determine the set of viral peptides presented to CD4+ T cells. Eight sites across the HCV genome were associated with HLA class II alleles implicated in infection outcome in this cohort (p ≤ 0.01; Fisher's exact test). We extended this analysis to chronic HCV infection (n = 351) for the common genotypes 1A and 3A. Variation at 38 sites across the HCV genome were associated with specific HLA class II alleles with no overlap between genotypes, suggestive of genotype-specific T cell targets, which has important implications for vaccine design. Here we show evidence of HCV adaptation to HLA class II-restricted CD4+ T cell pressure across the HCV genome in chronic HCV infection without a priori knowledge of CD4+ T cell epitopes.
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spelling oxford-uuid:aed01c48-4ee7-4114-a5f9-eb22a1c4c2c52022-03-27T03:45:20ZEvidence of CD4+ T cell-mediated immune pressure on the Hepatitis C virus genomeJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:aed01c48-4ee7-4114-a5f9-eb22a1c4c2c5EnglishSymplectic Elements at OxfordNature Publishing Group2018Lucas, MDeshpande, PJames, IRauch, APfafferott, KGaylard, EMerani, SPlauzolles, ALucas, AMcDonnell, WKalams, SPilkinton, MChastain, CBarnett, LProsser, AMallal, SFitzmaurice, KDrummer, HAnsari, MPedergnana, VBarnes, EJohn, MKelleher, DKlenerman, PGaudieri, SHepatitis C virus (HCV)-specific T cell responses are critical for immune control of infection. Viral adaptation to these responses, via mutations within regions of the virus targeted by CD8+ T cells, is associated with viral persistence. However, identifying viral adaptation to HCV-specific CD4+ T cell responses has been difficult although key to understanding anti-HCV immunity. In this context, HCV sequence and host genotype from a single source HCV genotype 1B cohort (n = 63) were analyzed to identify viral changes associated with specific human leucocyte antigen (HLA) class II alleles, as these variable host molecules determine the set of viral peptides presented to CD4+ T cells. Eight sites across the HCV genome were associated with HLA class II alleles implicated in infection outcome in this cohort (p ≤ 0.01; Fisher's exact test). We extended this analysis to chronic HCV infection (n = 351) for the common genotypes 1A and 3A. Variation at 38 sites across the HCV genome were associated with specific HLA class II alleles with no overlap between genotypes, suggestive of genotype-specific T cell targets, which has important implications for vaccine design. Here we show evidence of HCV adaptation to HLA class II-restricted CD4+ T cell pressure across the HCV genome in chronic HCV infection without a priori knowledge of CD4+ T cell epitopes.
spellingShingle Lucas, M
Deshpande, P
James, I
Rauch, A
Pfafferott, K
Gaylard, E
Merani, S
Plauzolles, A
Lucas, A
McDonnell, W
Kalams, S
Pilkinton, M
Chastain, C
Barnett, L
Prosser, A
Mallal, S
Fitzmaurice, K
Drummer, H
Ansari, M
Pedergnana, V
Barnes, E
John, M
Kelleher, D
Klenerman, P
Gaudieri, S
Evidence of CD4+ T cell-mediated immune pressure on the Hepatitis C virus genome
title Evidence of CD4+ T cell-mediated immune pressure on the Hepatitis C virus genome
title_full Evidence of CD4+ T cell-mediated immune pressure on the Hepatitis C virus genome
title_fullStr Evidence of CD4+ T cell-mediated immune pressure on the Hepatitis C virus genome
title_full_unstemmed Evidence of CD4+ T cell-mediated immune pressure on the Hepatitis C virus genome
title_short Evidence of CD4+ T cell-mediated immune pressure on the Hepatitis C virus genome
title_sort evidence of cd4 t cell mediated immune pressure on the hepatitis c virus genome
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