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 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.affiliation: The Lautenberg Center for General and Tumor Immunology, Institute for Medical Research Israel-Canada (IMRIC), Faculty of Medicine, Hebrew University Hadassah Medical School, Jerusalem 91120, Israel.
authors.forename: Yotam
authors.initials: Y
authors.lastname: Bar-On
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, Institute for Medical Research Israel-Canada (IMRIC), Faculty of Medicine, Hebrew University Hadassah Medical School, Jerusalem 91120, Israel.
authors.forename: Ariella
authors.initials: A
authors.lastname: Glasner
authors.affiliation: Central Virology Laboratory, Ministry of Health, Public Health Services, Chaim Sheba Medical Center, Tel Hashomer, Ramat-Gan 52662, Israel.|The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel.
authors.forename: Tal
authors.initials: T
authors.lastname: Meningher
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, Institute for Medical Research Israel-Canada (IMRIC), Faculty of Medicine, Hebrew University Hadassah Medical School, Jerusalem 91120, Israel.|Department of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona 74100, Israel.
authors.forename: Hagit
authors.initials: H
authors.lastname: Achdout
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, Institute for Medical Research Israel-Canada (IMRIC), Faculty of Medicine, Hebrew University Hadassah Medical School, Jerusalem 91120, Israel.
authors.forename: Chamutal
authors.initials: C
authors.lastname: Gur
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, Institute for Medical Research Israel-Canada (IMRIC), Faculty of Medicine, Hebrew University Hadassah Medical School, Jerusalem 91120, Israel.
authors.forename: Dikla
authors.initials: D
authors.lastname: Lankry
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, Institute for Medical Research Israel-Canada (IMRIC), Faculty of Medicine, Hebrew University Hadassah Medical School, Jerusalem 91120, Israel.
authors.forename: Alon
authors.initials: A
authors.lastname: Vitenshtein
authors.affiliation: National Laboratory for HIV Immunology, National HIV and Retrovirology Laboratories, Public Health Agency of Canada, Winnipeg R3E 3R2, Canada.|Department of Medical Microbiology, University of Manitoba, Winnipeg R3E 0J9, Canada.
authors.forename: Adrienne F A
authors.initials: AFA
authors.lastname: Meyers
authors.affiliation: Central Virology Laboratory, Ministry of Health, Public Health Services, Chaim Sheba Medical Center, Tel Hashomer, Ramat-Gan 52662, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Mandelboim
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, Institute for Medical Research Israel-Canada (IMRIC), Faculty of Medicine, Hebrew University Hadassah Medical School, Jerusalem 91120, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Mandelboim
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000378:metabolism; D006801:Humans; D057131:Immune Evasion / Q000187:drug effects; D053118:Influenza A Virus, H1N1 Subtype / Q000201:enzymology / Q000502:physiology; D053122:Influenza A Virus, H3N2 Subtype / Q000201:enzymology / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009975:Orthomyxoviridae / Q000201:enzymology* / Q000502:physiology; D053139:Oseltamivir / Q000494:pharmacology
chemical_list: D000950:Antigens, Ly; D004791:Enzyme Inhibitors; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D055627:Natural Cytotoxicity Triggering Receptor 1; C118384:Ncr1 protein, mouse; D053139:Oseltamivir; D009439:Neuraminidase