Human cytomegalovirus escapes immune recognition by NK cells through the downregulation of B7-H6 by the viral genes US18 and US20

Yoav Charpak-Amikam; Tobias Kubsch; Einat Seidel; Esther Oiknine-Djian; Noemi Cavaletto; Rachel Yamin; Dominik Schmiedel; Dana Wolf; Giorgio Gribaudo; Martin Messerle; Luka Cicin-Sain; Ofer Mandelboim

doi:10.1038/s41598-017-08866-2

Human cytomegalovirus escapes immune recognition by NK cells through the downregulation of B7-H6 by the viral genes US18 and US20

Yoav Charpak-Amikam, Tobias Kubsch, Einat Seidel, Esther Oiknine-Djian, Noemi Cavaletto, Rachel Yamin, Dominik Schmiedel, Dana Wolf, Giorgio Gribaudo, Martin Messerle, Luka Cicin-Sain, Ofer Mandelboim^*

^*Corresponding author for this work

Department of Immunology and Cancer Research

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

33 Scopus citations

Abstract

Human cytomegalovirus (HCMV) is a major human pathogen, causing serious diseases in immunocompromised populations and congenially infected neonates. One of the main immune cells acting against the virus are Natural Killer (NK) cells. Killing by NK cells is mediated by a small family of activating receptors such as NKp30 that interact with the cellular ligand B7-H6. The outcome of B7-H6-NKp30 interaction was, so far, mainly studied with regard to NK recognition and killing of tumors. Here, we demonstrated that the expression of B7-H6 is upregulated following HCMV infection and that HCMV uses two of its genes: US18 and US20, to interfere with B7-H6 surface expression, in a mechanism involving endosomal degradation, in order to evade NK cell recognition.

Original language	English
Article number	8661
Journal	Scientific Reports
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s41598-017-08866-2
State	Published - 1 Dec 2017

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© 2017 The Author(s).

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Charpak-Amikam, Y., Kubsch, T., Seidel, E., Oiknine-Djian, E., Cavaletto, N., Yamin, R., Schmiedel, D., Wolf, D., Gribaudo, G., Messerle, M., Cicin-Sain, L., & Mandelboim, O. (2017). Human cytomegalovirus escapes immune recognition by NK cells through the downregulation of B7-H6 by the viral genes US18 and US20. Scientific Reports, 7(1), Article 8661. https://doi.org/10.1038/s41598-017-08866-2

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abstract = "Human cytomegalovirus (HCMV) is a major human pathogen, causing serious diseases in immunocompromised populations and congenially infected neonates. One of the main immune cells acting against the virus are Natural Killer (NK) cells. Killing by NK cells is mediated by a small family of activating receptors such as NKp30 that interact with the cellular ligand B7-H6. The outcome of B7-H6-NKp30 interaction was, so far, mainly studied with regard to NK recognition and killing of tumors. Here, we demonstrated that the expression of B7-H6 is upregulated following HCMV infection and that HCMV uses two of its genes: US18 and US20, to interfere with B7-H6 surface expression, in a mechanism involving endosomal degradation, in order to evade NK cell recognition.",

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Charpak-Amikam, Y, Kubsch, T, Seidel, E, Oiknine-Djian, E, Cavaletto, N, Yamin, R, Schmiedel, D, Wolf, D, Gribaudo, G, Messerle, M, Cicin-Sain, L & Mandelboim, O 2017, 'Human cytomegalovirus escapes immune recognition by NK cells through the downregulation of B7-H6 by the viral genes US18 and US20', Scientific Reports, vol. 7, no. 1, 8661. https://doi.org/10.1038/s41598-017-08866-2

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AU - Kubsch, Tobias

AU - Seidel, Einat

AU - Oiknine-Djian, Esther

AU - Cavaletto, Noemi

AU - Yamin, Rachel

AU - Schmiedel, Dominik

AU - Wolf, Dana

AU - Gribaudo, Giorgio

AU - Messerle, Martin

AU - Cicin-Sain, Luka

AU - Mandelboim, Ofer

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Human cytomegalovirus escapes immune recognition by NK cells through the downregulation of B7-H6 by the viral genes US18 and US20

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