title: Elucidating the mechanisms of influenza virus recognition by Ncr1.
abstract: Natural killer (NK) cells are innate cytotoxic lymphocytes that specialize in the defense against viral infection and oncogenic transformation. Their action is tightly regulated by signals derived from inhibitory and activating receptors; the later include proteins such as the Natural Cytotoxicity Receptors (NCRs: NKp46, NKp44 and NKp30). Among the NCRs, NKp46 is the only receptor that has a mouse orthologue named Ncr1. NKp46/Ncr1 is also a unique marker expressed on NK and on Lymphoid tissue inducer (LTI) cells and it was implicated in the control of various viral infections, cancer and diabetes. We have previously shown that human NKp46 recognizes viral hemagglutinin (HA) in a sialic acid-dependent manner and that the O-glycosylation is essential for the NKp46 binding to viral HA. Here we studied the molecular interactions between Ncr1 and influenza viruses. We show that Ncr1 recognizes influenza virus in a sialic acid dependent manner and that N-glycosylation is important for this binding. Surprisingly we demonstrate that none of the predicted N-glycosilated residues of Ncr1 are essential for its binding to influenza virus and we thus conclude that other, yet unidentified N-glycosilated residues are responsible for its recognition. We have demonstrated that N glycosylation play little role in the recognition of mouse tumor cell lines and also showed the in-vivo importance of Ncr1 in the control of influenza virus infection by infecting C57BL/6 and BALB/c mice knockout for Ncr1 with influenza.
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, Institute for Medical Research Israel Canada, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: Ariella
authors.initials: A
authors.lastname: Glasner
authors.forename: Antonija
authors.initials: A
authors.lastname: Zurunic
authors.forename: Tal
authors.initials: T
authors.lastname: Meningher
authors.forename: Tihana
authors.initials: T
authors.lastname: Lenac Rovis
authors.forename: Pinchas
authors.initials: P
authors.lastname: Tsukerman
authors.forename: Yotam
authors.initials: Y
authors.lastname: Bar-On
authors.forename: Rachel
authors.initials: R
authors.lastname: Yamin
authors.forename: Adrienne F A
authors.initials: AF
authors.lastname: Meyers
authors.forename: Michal
authors.initials: M
authors.lastname: Mandeboim
authors.forename: Stipan
authors.initials: S
authors.lastname: Jonjic
authors.forename: Ofer
authors.initials: O
authors.lastname: Mandelboim
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000502:physiology*; D001483:Base Sequence; D017931:DNA Primers; D005434:Flow Cytometry; D051379:Mice; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000502:physiology*; D009975:Orthomyxoviridae / Q000502:physiology*; D016133:Polymerase Chain Reaction
chemical_list: D000950:Antigens, Ly; D017931:DNA Primers; D055627:Natural Cytotoxicity Triggering Receptor 1; C118384:Ncr1 protein, mouse