Inhibition of the NKp30 activating receptor by pp65 of human cytomegalovirus.
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.
Arnon
Tal I
TI
The Lautenberg Center for General and Tumor Immunology, The Hebrew University Hadassah Medical School, Jerusalem 91120, Israel.
Achdout
Hagit
H
Levi
Ofer
O
Markel
Gal
G
Saleh
Nivin
N
Katz
Gil
G
Gazit
Roi
R
Gonen-Gross
Tsufit
T
Hanna
Jacob
J
Nahari
Efrat
E
Porgador
Angel
A
Honigman
Alik
A
Plachter
Bodo
B
Mevorach
Dror
D
Wolf
Dana G
DG
Mandelboim
Ofer
O
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
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