title: Inhibition of the NKp30 activating receptor by pp65 of human cytomegalovirus.
abstract: Human cytomegalovirus, a chief pathogen in immunocompromised people, can persist in a healthy immunocompetent host throughout life without being eliminated by the immune system. Here we show that pp65, the main tegument protein of human cytomegalovirus, inhibited natural killer cell cytotoxicity by an interaction with the activating receptor NKp30. This interaction was direct and specific, leading to dissociation of the linked CD3zeta from NKp30 and, consequently, to reduced killing. Thus, pp65 is a ligand for the NKp30 receptor and demonstrates a unique mechanism by which an intracellular viral protein causes general suppression of natural killer cell cytotoxicity by specific interaction with an activating receptor.
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The Hebrew University Hadassah Medical School, Jerusalem 91120, Israel.
authors.forename: Tal I
authors.initials: TI
authors.lastname: Arnon
authors.forename: Hagit
authors.initials: H
authors.lastname: Achdout
authors.forename: Ofer
authors.initials: O
authors.lastname: Levi
authors.forename: Gal
authors.initials: G
authors.lastname: Markel
authors.forename: Nivin
authors.initials: N
authors.lastname: Saleh
authors.forename: Gil
authors.initials: G
authors.lastname: Katz
authors.forename: Roi
authors.initials: R
authors.lastname: Gazit
authors.forename: Tsufit
authors.initials: T
authors.lastname: Gonen-Gross
authors.forename: Jacob
authors.initials: J
authors.lastname: Hanna
authors.forename: Efrat
authors.initials: E
authors.lastname: Nahari
authors.forename: Angel
authors.initials: A
authors.lastname: Porgador
authors.forename: Alik
authors.initials: A
authors.lastname: Honigman
authors.forename: Bodo
authors.initials: B
authors.lastname: Plachter
authors.forename: Dror
authors.initials: D
authors.lastname: Mevorach
authors.forename: Dana G
authors.initials: DG
authors.lastname: Wolf
authors.forename: Ofer
authors.initials: O
authors.lastname: Mandelboim
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000502:physiology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005786:Gene Expression Regulation; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051379:Mice; D055628:Natural Cytotoxicity Triggering Receptor 3; D010750:Phosphoproteins / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000378:metabolism; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D007141:Immunoglobulin Fc Fragments; D008562:Membrane Glycoproteins; C431710:NCR3 protein, human; D055628:Natural Cytotoxicity Triggering Receptor 3; D010750:Phosphoproteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa