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The human 2B4 and NTB-A receptors bind the influenza viral hemagglutinin and co-stimulate NK cell cytotoxicity

Natural Killer (NK) cells are critical in the defense against viruses in general and against influenza in particular. We previously demonstrated that the activating NK cell receptor NKp46 is involved in the killing of influenza-virus infected cells through its interaction with viral hemagglutinin (H...

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Autores principales: Duev-Cohen, Alexandra, Bar-On, Yotam, Glasner, Ariella, Berhani, Orit, Ophir, Yael, Levi-Schaffer, Francesca, Mandelboim, Michal, Mandelboim, Ofer
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4914344/
https://www.ncbi.nlm.nih.gov/pubmed/26919106
http://dx.doi.org/10.18632/oncotarget.7597
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author Duev-Cohen, Alexandra
Bar-On, Yotam
Glasner, Ariella
Berhani, Orit
Ophir, Yael
Levi-Schaffer, Francesca
Mandelboim, Michal
Mandelboim, Ofer
author_facet Duev-Cohen, Alexandra
Bar-On, Yotam
Glasner, Ariella
Berhani, Orit
Ophir, Yael
Levi-Schaffer, Francesca
Mandelboim, Michal
Mandelboim, Ofer
author_sort Duev-Cohen, Alexandra
collection PubMed
description Natural Killer (NK) cells are critical in the defense against viruses in general and against influenza in particular. We previously demonstrated that the activating NK cell receptor NKp46 is involved in the killing of influenza-virus infected cells through its interaction with viral hemagglutinin (HA). Furthermore, the recognition by NKp46 and consequent elimination of influenza infected cells were determined to be sialic-acid dependent. Here, we show that the human co-activating receptors 2B4 and NTB-A directly recognize the viral HA protein and co-stimulate killing by NK cells. We demonstrate that the 2B4/NTB-A-HA interactions require the sialylation of these receptors, and we identified the binding sites mediating these interactions. We also show that the virus counters these interactions through its neuraminidase (NA) protein. These results emphasize the critical role played by NK cells in eliminating influenza, a significant cause of worldwide morbidity and mortality.
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spelling pubmed-49143442016-07-11 The human 2B4 and NTB-A receptors bind the influenza viral hemagglutinin and co-stimulate NK cell cytotoxicity Duev-Cohen, Alexandra Bar-On, Yotam Glasner, Ariella Berhani, Orit Ophir, Yael Levi-Schaffer, Francesca Mandelboim, Michal Mandelboim, Ofer Oncotarget Research Paper Natural Killer (NK) cells are critical in the defense against viruses in general and against influenza in particular. We previously demonstrated that the activating NK cell receptor NKp46 is involved in the killing of influenza-virus infected cells through its interaction with viral hemagglutinin (HA). Furthermore, the recognition by NKp46 and consequent elimination of influenza infected cells were determined to be sialic-acid dependent. Here, we show that the human co-activating receptors 2B4 and NTB-A directly recognize the viral HA protein and co-stimulate killing by NK cells. We demonstrate that the 2B4/NTB-A-HA interactions require the sialylation of these receptors, and we identified the binding sites mediating these interactions. We also show that the virus counters these interactions through its neuraminidase (NA) protein. These results emphasize the critical role played by NK cells in eliminating influenza, a significant cause of worldwide morbidity and mortality. Impact Journals LLC 2016-02-22 /pmc/articles/PMC4914344/ /pubmed/26919106 http://dx.doi.org/10.18632/oncotarget.7597 Text en Copyright: © 2016 Duev-Cohen et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Duev-Cohen, Alexandra
Bar-On, Yotam
Glasner, Ariella
Berhani, Orit
Ophir, Yael
Levi-Schaffer, Francesca
Mandelboim, Michal
Mandelboim, Ofer
The human 2B4 and NTB-A receptors bind the influenza viral hemagglutinin and co-stimulate NK cell cytotoxicity
title The human 2B4 and NTB-A receptors bind the influenza viral hemagglutinin and co-stimulate NK cell cytotoxicity
title_full The human 2B4 and NTB-A receptors bind the influenza viral hemagglutinin and co-stimulate NK cell cytotoxicity
title_fullStr The human 2B4 and NTB-A receptors bind the influenza viral hemagglutinin and co-stimulate NK cell cytotoxicity
title_full_unstemmed The human 2B4 and NTB-A receptors bind the influenza viral hemagglutinin and co-stimulate NK cell cytotoxicity
title_short The human 2B4 and NTB-A receptors bind the influenza viral hemagglutinin and co-stimulate NK cell cytotoxicity
title_sort human 2b4 and ntb-a receptors bind the influenza viral hemagglutinin and co-stimulate nk cell cytotoxicity
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4914344/
https://www.ncbi.nlm.nih.gov/pubmed/26919106
http://dx.doi.org/10.18632/oncotarget.7597
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