Inhibition of the NKp30 activating receptor by pp65 of human cytomegalovirus

Tal I. Arnon; Hagit Achdout; Ofer Levi; Gal Markel; Nivin Saleh; Gil Katz; Roi Gazit; Tsufit Gonen-Gross; Jacob Hanna; Efrat Nahari; Angel Porgador; Alik Honigman; Bodo Plachter; Dror Mevorach; Dana G. Wolf; Ofer Mandelboim

doi:10.1038/ni1190

Inhibition of the NKp30 activating receptor by pp65 of human cytomegalovirus

Tal I. Arnon, Hagit Achdout, Ofer Levi, Gal Markel, Nivin Saleh, Gil Katz, Roi Gazit, Tsufit Gonen-Gross, Jacob Hanna, Efrat Nahari, Angel Porgador, Alik Honigman, Bodo Plachter, Dror Mevorach, Dana G. Wolf, Ofer Mandelboim^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

310 Scopus citations

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 CD3ζ 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.

Original language	English
Pages (from-to)	515-523
Number of pages	9
Journal	Nature Immunology
Volume	6
Issue number	5
DOIs	https://doi.org/10.1038/ni1190
State	Published - 2005

Bibliographical note

Funding Information:
We thank E. Vivier, H. Hengel and M. Lopez-Botet for suggestions; and D. Davis and D. Coen for critically reading the manuscript. Supported by the Israel Science Foundation (O.M. and D.W.), European Commission (QLK2-CT-2002-011112 to O.M.), Hadassah Women’s Health Research Foundation (D.W.) and Deutsche Forschungsgemeimschaft (SFB490 to B.P.).

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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 CD3ζ 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.",

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AU - Saleh, Nivin

AU - Katz, Gil

AU - Gazit, Roi

AU - Gonen-Gross, Tsufit

AU - Hanna, Jacob

AU - Nahari, Efrat

AU - Porgador, Angel

AU - Honigman, Alik

AU - Plachter, Bodo

AU - Mevorach, Dror

AU - Wolf, Dana G.

AU - Mandelboim, Ofer

N1 - Funding Information: We thank E. Vivier, H. Hengel and M. Lopez-Botet for suggestions; and D. Davis and D. Coen for critically reading the manuscript. Supported by the Israel Science Foundation (O.M. and D.W.), European Commission (QLK2-CT-2002-011112 to O.M.), Hadassah Women’s Health Research Foundation (D.W.) and Deutsche Forschungsgemeimschaft (SFB490 to B.P.).

PY - 2005

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N2 - 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 CD3ζ 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.

AB - 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 CD3ζ 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.

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Inhibition of the NKp30 activating receptor by pp65 of human cytomegalovirus

Abstract

Bibliographical note

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