title: Influenza virus uses its neuraminidase protein to evade the recognition of two activating NK cell receptors.
abstract: Natural Killer (NK) cells play a central role in the defense against viral infections and in the elimination of transformed cells. The recognition of pathogen-infected and tumor cells is controlled by inhibitory and activating receptors. We have previously shown that among the activating (killer) NK cell receptors the natural cytotoxicity receptors, NKp44 and NKp46, interact with the viral hemagglutinin (HA) protein expressed on the cell surface of influenza-virus-infected cells. We further showed that the interaction between NKp44/NKp46 and viral HA is sialic-acid dependent and that the recognition of HA by NKp44 and NKp46 leads to the elimination of the infected cells. Here we demonstrate that the influenza virus developed a counter-attack mechanism and that the virus uses its neuraminidase (NA) protein to prevent the recognition of HA by both the NKp44 and NKp46 receptors, resulting in reduced elimination of the infected cells by NK cells.
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute Israel-Canada of the Faculty of Medicine (IMRIC), the Hebrew University Hadassah Medical School, Jerusalem.
authors.forename: Yotam
authors.initials: Y
authors.lastname: Bar-On
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute Israel-Canada of the Faculty of Medicine (IMRIC), the Hebrew University Hadassah Medical School, Jerusalem.
authors.forename: Einat
authors.initials: E
authors.lastname: Seidel
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute Israel-Canada of the Faculty of Medicine (IMRIC), the Hebrew University Hadassah Medical School, Jerusalem.
authors.forename: Pinchas
authors.initials: P
authors.lastname: Tsukerman
authors.affiliation: Central Virology Laboratory, Ministry of Health, Public Health Services, Chaim, Sheba Medical Center, Ramat-Gan, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Mandelboim
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute Israel-Canada of the Faculty of Medicine (IMRIC), the Hebrew University Hadassah Medical School, Jerusalem.
authors.forename: Ofer
authors.initials: O
authors.lastname: Mandelboim
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006388:Hemagglutinins / Q000378:metabolism; D006801:Humans; D009980:Influenza A virus / Q000502:physiology*; D051379:Mice; D009439:Neuraminidase / Q000235:genetics / Q000378:metabolism*; D055607:Receptors, Natural Killer Cell / Q000378:metabolism*
chemical_list: D006388:Hemagglutinins; D055607:Receptors, Natural Killer Cell; D009439:Neuraminidase
keywords: NK cells; NKp44; NKp46; immune evasion; influenza virus; neuraminidase