Neuraminidase-Mediated, NKp46-Dependent Immune-Evasion Mechanism of Influenza Viruses

Yotam Bar-On; Ariella Glasner; Tal Meningher; Hagit Achdout; Chamutal Gur; Dikla Lankry; Alon Vitenshtein; Adrienne F.A. Meyers; Michal Mandelboim; Ofer Mandelboim

doi:10.1016/j.celrep.2013.03.034

Neuraminidase-Mediated, NKp46-Dependent Immune-Evasion Mechanism of Influenza Viruses

Yotam Bar-On, Ariella Glasner, Tal Meningher, Hagit Achdout, Chamutal Gur, Dikla Lankry, Alon Vitenshtein, Adrienne F.A. Meyers, Michal Mandelboim, Ofer Mandelboim

Department of Immunology and Cancer Research

The Hebrew University of Jerusalem

Research output: Contribution to journal › Article › peer-review

Abstract

Natural killer (NK) cells play an essential role in the defense against influenza virus, one of the deadliest respiratory viruses known today. The NKp46 receptor, expressed by NK cells, is critical for controlling influenza infections, as influenza-virus-infected cells are eliminated through the recognition of the viral hemagglutinin (HA) protein by NKp46. Here, we describe an immune-evasion mechanism of influenza viruses that is mediated by the neuraminidase (NA) protein. By using various NA blockers, we show that NA removes sialic acid residues from NKp46 and that this leads to reduced recognition of HA. Furthermore, we provide invivo and invitro evidence for the existence of this NA-mediated, NKp46-dependent immune-evasion mechanism and demonstrate that NA inhibitors, which are commonly used for the treatment of influenza infections, are useful not only as blockers of virus budding but also as boosters of NKp46 recognition.

Original language	English
Pages (from-to)	1044-1050
Number of pages	7
Journal	Cell Reports
Volume	3
Issue number	4
DOIs	https://doi.org/10.1016/j.celrep.2013.03.034
State	Published - 25 Apr 2013

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

All Science Journal Classification (ASJC) codes

General Biochemistry,Genetics and Molecular Biology

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10.1016/j.celrep.2013.03.034

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title = "Neuraminidase-Mediated, NKp46-Dependent Immune-Evasion Mechanism of Influenza Viruses",

abstract = "Natural killer (NK) cells play an essential role in the defense against influenza virus, one of the deadliest respiratory viruses known today. The NKp46 receptor, expressed by NK cells, is critical for controlling influenza infections, as influenza-virus-infected cells are eliminated through the recognition of the viral hemagglutinin (HA) protein by NKp46. Here, we describe an immune-evasion mechanism of influenza viruses that is mediated by the neuraminidase (NA) protein. By using various NA blockers, we show that NA removes sialic acid residues from NKp46 and that this leads to reduced recognition of HA. Furthermore, we provide invivo and invitro evidence for the existence of this NA-mediated, NKp46-dependent immune-evasion mechanism and demonstrate that NA inhibitors, which are commonly used for the treatment of influenza infections, are useful not only as blockers of virus budding but also as boosters of NKp46 recognition.",

author = "Yotam Bar-On and Ariella Glasner and Tal Meningher and Hagit Achdout and Chamutal Gur and Dikla Lankry and Alon Vitenshtein and Meyers, \{Adrienne F.A.\} and Michal Mandelboim and Ofer Mandelboim",

note = "Funding Information: We thank J. Yewdell for kindly providing the anti-HA and anti-NA antibodies. This study was supported by a Croatia Israel Research Grant, a MOST-DKFZ Research Grant, an ICRF Professorship Grant, an ERC Advanced Grant, and grants from the Israeli Science Foundation, the Israeli ICORE, and the Association for International Cancer Research (all to O.M.). O.M. is a Crown Professor of Molecular Immunology.",

year = "2013",

month = apr,

day = "25",

doi = "10.1016/j.celrep.2013.03.034",

language = "الإنجليزيّة",

volume = "3",

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issn = "2211-1247",

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T1 - Neuraminidase-Mediated, NKp46-Dependent Immune-Evasion Mechanism of Influenza Viruses

AU - Bar-On, Yotam

AU - Glasner, Ariella

AU - Meningher, Tal

AU - Achdout, Hagit

AU - Gur, Chamutal

AU - Lankry, Dikla

AU - Vitenshtein, Alon

AU - Meyers, Adrienne F.A.

AU - Mandelboim, Michal

AU - Mandelboim, Ofer

N1 - Funding Information: We thank J. Yewdell for kindly providing the anti-HA and anti-NA antibodies. This study was supported by a Croatia Israel Research Grant, a MOST-DKFZ Research Grant, an ICRF Professorship Grant, an ERC Advanced Grant, and grants from the Israeli Science Foundation, the Israeli ICORE, and the Association for International Cancer Research (all to O.M.). O.M. is a Crown Professor of Molecular Immunology.

PY - 2013/4/25

Y1 - 2013/4/25

N2 - Natural killer (NK) cells play an essential role in the defense against influenza virus, one of the deadliest respiratory viruses known today. The NKp46 receptor, expressed by NK cells, is critical for controlling influenza infections, as influenza-virus-infected cells are eliminated through the recognition of the viral hemagglutinin (HA) protein by NKp46. Here, we describe an immune-evasion mechanism of influenza viruses that is mediated by the neuraminidase (NA) protein. By using various NA blockers, we show that NA removes sialic acid residues from NKp46 and that this leads to reduced recognition of HA. Furthermore, we provide invivo and invitro evidence for the existence of this NA-mediated, NKp46-dependent immune-evasion mechanism and demonstrate that NA inhibitors, which are commonly used for the treatment of influenza infections, are useful not only as blockers of virus budding but also as boosters of NKp46 recognition.

AB - Natural killer (NK) cells play an essential role in the defense against influenza virus, one of the deadliest respiratory viruses known today. The NKp46 receptor, expressed by NK cells, is critical for controlling influenza infections, as influenza-virus-infected cells are eliminated through the recognition of the viral hemagglutinin (HA) protein by NKp46. Here, we describe an immune-evasion mechanism of influenza viruses that is mediated by the neuraminidase (NA) protein. By using various NA blockers, we show that NA removes sialic acid residues from NKp46 and that this leads to reduced recognition of HA. Furthermore, we provide invivo and invitro evidence for the existence of this NA-mediated, NKp46-dependent immune-evasion mechanism and demonstrate that NA inhibitors, which are commonly used for the treatment of influenza infections, are useful not only as blockers of virus budding but also as boosters of NKp46 recognition.

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U2 - 10.1016/j.celrep.2013.03.034

DO - 10.1016/j.celrep.2013.03.034

M3 - مقالة

C2 - 23602571

SN - 2211-1247

VL - 3

SP - 1044

EP - 1050

JO - Cell Reports

JF - Cell Reports

IS - 4

ER -

Neuraminidase-Mediated, NKp46-Dependent Immune-Evasion Mechanism of Influenza Viruses

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