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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


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 languageAmerican English
Pages (from-to)1044-1050
Number of pages7
JournalCell Reports
Issue number4
StatePublished - 25 Apr 2013

Bibliographical 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.


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