Imperial College London
Alternate

ProfessorFrancesGotch

Faculty of Medicine, Department of Infectious Disease

Emeritus Professor of Immunology
 
 
 
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Contact

 

+44 (0)20 3315 8257f.gotch

 
 
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Assistant

 

Mrs Julie James +44 (0)20 3315 8258

 
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Location

 

J 2 12Chelsea and Westminster HospitalChelsea and Westminster Campus

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Summary

 

Publications

Citation

BibTex format

@article{Matthews:2011:10.1002/eji.201040661,
author = {Matthews, NC and Goodier, MR and Robey, RC and Bower, M and Gotch, FM},
doi = {10.1002/eji.201040661},
journal = {European Journal of Immunology},
pages = {1958--1968},
title = {Killing of Kaposi's sarcoma-associated herpesvirus-infected fibroblasts during latent infection by activated natural killer cells},
url = {http://dx.doi.org/10.1002/eji.201040661},
volume = {41},
year = {2011}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) establishes life-long infection by evading clearance by the host immune system. In de novo infection and lytic replication, KSHV escapes cytotoxic T cells and NK cells through downregulation of MHC class-I and ICAM-1 molecules and associated antigens involved in forming and sustaining the immunological synapse. However, the efficacy of such mechanisms in the context of the predominantly latent KSHV infection reported in Kaposi's sarcoma (KS) lesions is unclear. Using primary dermal fibroblasts in a novel in vitro model of chronic latent KSHV infection, we generated target cells with viral loads similar to those in spindle cells extracted from KS lesions. We show that latently KSHV-infected fibroblasts had normal levels of MHC-class I, ICAM-1, HLA-E and NKG2D ligand expression, were resistant to NK-cell natural cytotoxicity and were highly susceptible to killing by cytokine-activated immunocompetent NK cells. KSHV-infected fibroblasts expressed normal levels of IFN-γR1 and responded to exogenous IFN-γ by upregulating MHC class I, ICAM-1 and HLA-E and resisting activated NK-cell killing. These data demonstrate that physiologically relevant levels of latent KSHV infection in primary cells cause limited activation of resting NK cells and confer little specific resistance to control by activated NK cells.
AU  - Matthews,NC
AU  - Goodier,MR
AU  - Robey,RC
AU  - Bower,M
AU  - Gotch,FM
DO  - 10.1002/eji.201040661
EP  - 1968
PY  - 2011///
SN  - 1521-4141
SP  - 1958
TI  - Killing of Kaposi's sarcoma-associated herpesvirus-infected fibroblasts during latent infection by activated natural killer cells
T2  - European Journal of Immunology
UR  - http://dx.doi.org/10.1002/eji.201040661
UR  - http://hdl.handle.net/10044/1/38374
VL  - 41
ER  -
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