Imperial College London
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ProfessorChristopherChiu

Faculty of Medicine, Department of Infectious Disease

Professor of Infectious Diseases
 
 
 
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Contact

 

+44 (0)20 3313 2301c.chiu Website

 
 
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Location

 

8N.15Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Chiu:2014:10.1371/journal.ppat.1004008,
author = {Chiu, C and McCausland, M and Sidney, J and Duh, F-M and Rouphael, N and Mehta, A and Mulligan, M and Carrington, M and Wieland, A and Sullivan, NL and Weinberg, A and Levin, MJ and Pulendran, B and Peters, B and Sette, A and Ahmed, R},
doi = {10.1371/journal.ppat.1004008},
journal = {PLoS Pathogens},
pages = {1--12},
title = {Broadly reactive human CD8 T cells that recognize an epitope conserved between VZV, HSV and EBV},
url = {http://dx.doi.org/10.1371/journal.ppat.1004008},
volume = {10},
year = {2014}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Human herpesviruses are important causes of potentially severe chronic infections for which T cells are believed to be necessary for control. In order to examine the role of virus-specific CD8 T cells against Varicella Zoster Virus (VZV), we generated a comprehensive panel of potential epitopes predicted in silico and screened for T cell responses in healthy VZV seropositive donors. We identified a dominant HLA-A0201-restricted epitope in the VZV ribonucleotide reductase subunit 2 and used a tetramer to analyze the phenotype and function of epitope-specific CD8 T cells. Interestingly, CD8 T cells responding to this VZV epitope also recognized homologous epitopes, not only in the other α-herpesviruses, HSV-1 and HSV-2, but also the γ-herpesvirus, EBV. Responses against these epitopes did not depend on previous infection with the originating virus, thus indicating the cross-reactive nature of this T cell population. Between individuals, the cells demonstrated marked phenotypic heterogeneity. This was associated with differences in functional capacity related to increased inhibitory receptor expression (including PD-1) along with decreased expression of co-stimulatory molecules that potentially reflected their stimulation history. Vaccination with the live attenuated Zostavax vaccine did not efficiently stimulate a proliferative response in this epitope-specific population. Thus, we identified a human CD8 T cell epitope that is conserved in four clinically important herpesviruses but that was poorly boosted by the current adult VZV vaccine. We discuss the concept of a “pan-herpesvirus” vaccine that this discovery raises and the hurdles that may need to be overcome in order to achieve this.
AU  - Chiu,C
AU  - McCausland,M
AU  - Sidney,J
AU  - Duh,F-M
AU  - Rouphael,N
AU  - Mehta,A
AU  - Mulligan,M
AU  - Carrington,M
AU  - Wieland,A
AU  - Sullivan,NL
AU  - Weinberg,A
AU  - Levin,MJ
AU  - Pulendran,B
AU  - Peters,B
AU  - Sette,A
AU  - Ahmed,R
DO  - 10.1371/journal.ppat.1004008
EP  - 12
PY  - 2014///
SN  - 1553-7366
SP  - 1
TI  - Broadly reactive human CD8 T cells that recognize an epitope conserved between VZV, HSV and EBV
T2  - PLoS Pathogens
UR  - http://dx.doi.org/10.1371/journal.ppat.1004008
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000337470300050&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004008
UR  - http://hdl.handle.net/10044/1/82334
VL  - 10
ER  -
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