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Killing of Kaposi's sarcoma-associated herpesvirus-infected fibroblasts during latent infection by activated natural killer cells

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 antige...

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Autores principales: Matthews, Nick C, Goodier, Martin R, Robey, Rebecca C, Bower, Mark, Gotch, Frances M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: WILEY-VCH Verlag 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3485667/
https://www.ncbi.nlm.nih.gov/pubmed/21509779
http://dx.doi.org/10.1002/eji.201040661
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author Matthews, Nick C
Goodier, Martin R
Robey, Rebecca C
Bower, Mark
Gotch, Frances M
author_facet Matthews, Nick C
Goodier, Martin R
Robey, Rebecca C
Bower, Mark
Gotch, Frances M
author_sort Matthews, Nick C
collection PubMed
description 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.
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spelling pubmed-34856672012-11-05 Killing of Kaposi's sarcoma-associated herpesvirus-infected fibroblasts during latent infection by activated natural killer cells Matthews, Nick C Goodier, Martin R Robey, Rebecca C Bower, Mark Gotch, Frances M Eur J Immunol Immunity to Infection 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. WILEY-VCH Verlag 2011-07 2011-05-27 /pmc/articles/PMC3485667/ /pubmed/21509779 http://dx.doi.org/10.1002/eji.201040661 Text en Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://wileyonlinelibrary.com/onlineopen#OnlineOpen_Terms
spellingShingle Immunity to Infection
Matthews, Nick C
Goodier, Martin R
Robey, Rebecca C
Bower, Mark
Gotch, Frances M
Killing of Kaposi's sarcoma-associated herpesvirus-infected fibroblasts during latent infection by activated natural killer cells
title Killing of Kaposi's sarcoma-associated herpesvirus-infected fibroblasts during latent infection by activated natural killer cells
title_full Killing of Kaposi's sarcoma-associated herpesvirus-infected fibroblasts during latent infection by activated natural killer cells
title_fullStr Killing of Kaposi's sarcoma-associated herpesvirus-infected fibroblasts during latent infection by activated natural killer cells
title_full_unstemmed Killing of Kaposi's sarcoma-associated herpesvirus-infected fibroblasts during latent infection by activated natural killer cells
title_short Killing of Kaposi's sarcoma-associated herpesvirus-infected fibroblasts during latent infection by activated natural killer cells
title_sort killing of kaposi's sarcoma-associated herpesvirus-infected fibroblasts during latent infection by activated natural killer cells
topic Immunity to Infection
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3485667/
https://www.ncbi.nlm.nih.gov/pubmed/21509779
http://dx.doi.org/10.1002/eji.201040661
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