Inhibition of the NKp30 activating receptor by pp65 of human cytomegalovirus.

Arnon TI., Achdout H., Levi O., Markel G., Saleh N., Katz G., Gazit R., Gonen-Gross T., Hanna J., Nahari E., Porgador A., Honigman A., Plachter B., Mevorach D., Wolf DG., Mandelboim O.

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.

DOI

10.1038/ni1190

Type

Journal article

Journal

Nat Immunol

Publication Date

05/2005

Volume

6

Pages

515 - 523

Keywords

Animals, Cells, Cultured, Cytomegalovirus, Cytotoxicity, Immunologic, Gene Expression Regulation, Humans, Immunoglobulin Fc Fragments, Killer Cells, Natural, Kinetics, Membrane Glycoproteins, Mice, Natural Cytotoxicity Triggering Receptor 3, Phosphoproteins, Protein Binding, Receptors, Cell Surface, Receptors, Immunologic, Viral Matrix Proteins

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