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 in vivo and in vitro 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.

• Authors: Yotam Bar-On, Ariella Glasner, Tal Meningher, Hagit Achdout, Chamutal Gur, Dikla Lankry, Alon Vitenshtein, Adrienne F A Meyers, Michal Mandelboim, Ofer Mandelboim
• Journal: Cell reports (Cell Rep) Vol. 3 Issue 4 Pg. 1044-50 (Apr 25 2013) ISSN: 2211-1247 [Electronic] United States
• PMID: 23602571 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antigens, Ly
• Enzyme Inhibitors
• Hemagglutinin Glycoproteins, Influenza Virus
• Natural Cytotoxicity Triggering Receptor 1
• Ncr1 protein, mouse
• Oseltamivir
• Neuraminidase

Topics

• Animals
• Antigens, Ly (genetics, metabolism)
• Cell Line, Tumor
• Enzyme Inhibitors (pharmacology)
• Hemagglutinin Glycoproteins, Influenza Virus (metabolism)
• Humans
• Immune Evasion (drug effects)
• Influenza A Virus, H1N1 Subtype (enzymology, physiology)
• Influenza A Virus, H3N2 Subtype (enzymology, physiology)
• Killer Cells, Natural (immunology, metabolism)
• Mice
• Mice, Knockout
• Natural Cytotoxicity Triggering Receptor 1 (deficiency, genetics, metabolism)
• Neuraminidase (antagonists & inhibitors, metabolism)
• Orthomyxoviridae (enzymology, physiology)
• Oseltamivir (pharmacology)