HSV1 MicroRNA Modulation of GPI Anchoring and Downstream Immune Evasion

Jonatan Enk; Assi Levi; Yiska Weisblum; Rachel Yamin; Yoav Charpak-Amikam; Dana G. Wolf; Ofer Mandelboim

doi:10.1016/j.celrep.2016.09.077

HSV1 MicroRNA Modulation of GPI Anchoring and Downstream Immune Evasion

Jonatan Enk, Assi Levi, Yiska Weisblum, Rachel Yamin, Yoav Charpak-Amikam, Dana G. Wolf, Ofer Mandelboim^*

^*Corresponding author for this work

Department of Immunology and Cancer Research

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

30 Scopus citations

Abstract

Herpes simplex virus 1 (HSV1) is a ubiquitous human pathogen that utilizes variable mechanisms to evade immune surveillance. The glycosylphosphatidylinositol (GPI) anchoring pathway is a multistep process in which a myriad of different proteins are covalently attached to a GPI moiety to be presented on the cell surface. Among the different GPI-anchored proteins there are many with immunological importance. We present evidence that the HSV1-encoded miR H8 directly targets PIGT, a member of the protein complex that covalently attaches proteins to GPI in the final step of GPI anchoring. This results in a membrane down-modulation of several different immune-related, GPI-anchored proteins, including ligands for natural killer-activating receptors and the prominent viral restriction factor tetherin. Thus, we suggest that by utilizing just one of dozens of miRNAs encoded by HSV1, the virus can counteract the host immune response at several key points.

Original language	American English
Pages (from-to)	949-956
Number of pages	8
Journal	Cell Reports
Volume	17
Issue number	4
DOIs	https://doi.org/10.1016/j.celrep.2016.09.077
State	Published - 18 Oct 2016

Bibliographical note

Funding Information:
This study was supported by the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement 320473-BacNK. Further support came from the Israel Science Foundation, the GIF Foundation, the ICRF professorship grant, the Israeli Science Foundation, the Helmholtz Israel grant, and the Rosetrees Trust (all to O.M.). O.M. is a Crown Professor of Molecular Immunology.

Publisher Copyright:
© 2016 The Author(s)

Keywords

GPI anchoring
HSV1
NK cells
immune evasion
microRNA
tetherin

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10.1016/j.celrep.2016.09.077

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title = "HSV1 MicroRNA Modulation of GPI Anchoring and Downstream Immune Evasion",

abstract = "Herpes simplex virus 1 (HSV1) is a ubiquitous human pathogen that utilizes variable mechanisms to evade immune surveillance. The glycosylphosphatidylinositol (GPI) anchoring pathway is a multistep process in which a myriad of different proteins are covalently attached to a GPI moiety to be presented on the cell surface. Among the different GPI-anchored proteins there are many with immunological importance. We present evidence that the HSV1-encoded miR H8 directly targets PIGT, a member of the protein complex that covalently attaches proteins to GPI in the final step of GPI anchoring. This results in a membrane down-modulation of several different immune-related, GPI-anchored proteins, including ligands for natural killer-activating receptors and the prominent viral restriction factor tetherin. Thus, we suggest that by utilizing just one of dozens of miRNAs encoded by HSV1, the virus can counteract the host immune response at several key points.",

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author = "Jonatan Enk and Assi Levi and Yiska Weisblum and Rachel Yamin and Yoav Charpak-Amikam and Wolf, {Dana G.} and Ofer Mandelboim",

note = "Funding Information: This study was supported by the European Research Council under the European Union{\textquoteright}s Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement 320473-BacNK. Further support came from the Israel Science Foundation, the GIF Foundation, the ICRF professorship grant, the Israeli Science Foundation, the Helmholtz Israel grant, and the Rosetrees Trust (all to O.M.). O.M. is a Crown Professor of Molecular Immunology. Publisher Copyright: {\textcopyright} 2016 The Author(s)",

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AU - Charpak-Amikam, Yoav

AU - Wolf, Dana G.

AU - Mandelboim, Ofer

N1 - Funding Information: This study was supported by the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement 320473-BacNK. Further support came from the Israel Science Foundation, the GIF Foundation, the ICRF professorship grant, the Israeli Science Foundation, the Helmholtz Israel grant, and the Rosetrees Trust (all to O.M.). O.M. is a Crown Professor of Molecular Immunology. Publisher Copyright: © 2016 The Author(s)

PY - 2016/10/18

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N2 - Herpes simplex virus 1 (HSV1) is a ubiquitous human pathogen that utilizes variable mechanisms to evade immune surveillance. The glycosylphosphatidylinositol (GPI) anchoring pathway is a multistep process in which a myriad of different proteins are covalently attached to a GPI moiety to be presented on the cell surface. Among the different GPI-anchored proteins there are many with immunological importance. We present evidence that the HSV1-encoded miR H8 directly targets PIGT, a member of the protein complex that covalently attaches proteins to GPI in the final step of GPI anchoring. This results in a membrane down-modulation of several different immune-related, GPI-anchored proteins, including ligands for natural killer-activating receptors and the prominent viral restriction factor tetherin. Thus, we suggest that by utilizing just one of dozens of miRNAs encoded by HSV1, the virus can counteract the host immune response at several key points.

AB - Herpes simplex virus 1 (HSV1) is a ubiquitous human pathogen that utilizes variable mechanisms to evade immune surveillance. The glycosylphosphatidylinositol (GPI) anchoring pathway is a multistep process in which a myriad of different proteins are covalently attached to a GPI moiety to be presented on the cell surface. Among the different GPI-anchored proteins there are many with immunological importance. We present evidence that the HSV1-encoded miR H8 directly targets PIGT, a member of the protein complex that covalently attaches proteins to GPI in the final step of GPI anchoring. This results in a membrane down-modulation of several different immune-related, GPI-anchored proteins, including ligands for natural killer-activating receptors and the prominent viral restriction factor tetherin. Thus, we suggest that by utilizing just one of dozens of miRNAs encoded by HSV1, the virus can counteract the host immune response at several key points.

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KW - NK cells

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HSV1 MicroRNA Modulation of GPI Anchoring and Downstream Immune Evasion

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