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.
authors.affiliation: The Lautenberg Center of General and Tumor Immunology, IMRIC, The Hebrew University Faculty of Medicine, Jerusalem 91120, Israel.
authors.forename: Jonatan
authors.initials: J
authors.lastname: Enk
authors.affiliation: Photodermatosis Clinic and Laser Unit, Dermatology Department, Rabin Medical Center, Petah Tikva 4941492, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
authors.forename: Assi
authors.initials: A
authors.lastname: Levi
authors.affiliation: Clinical Virology Unit, Hadassah Hebrew University Medical Center, Jerusalem 91120, Israel; Department of Biochemistry and the Chanock Center for Virology, IMRIC, The Hebrew University Faculty of Medicine, Jerusalem 91120, Israel.
authors.forename: Yiska
authors.initials: Y
authors.lastname: Weisblum
authors.affiliation: The Lautenberg Center of General and Tumor Immunology, IMRIC, The Hebrew University Faculty of Medicine, Jerusalem 91120, Israel.
authors.forename: Rachel
authors.initials: R
authors.lastname: Yamin
authors.affiliation: The Lautenberg Center of General and Tumor Immunology, IMRIC, The Hebrew University Faculty of Medicine, Jerusalem 91120, Israel.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Charpak-Amikam
authors.affiliation: Clinical Virology Unit, Hadassah Hebrew University Medical Center, Jerusalem 91120, Israel.
authors.forename: Dana G
authors.initials: DG
authors.lastname: Wolf
authors.affiliation: The Lautenberg Center of General and Tumor Immunology, IMRIC, The Hebrew University Faculty of Medicine, Jerusalem 91120, Israel. Electronic address: oferm@ekmd.huji.ac.il.
authors.forename: Ofer
authors.initials: O
authors.lastname: Mandelboim
mesh_terms: D000217:Acyltransferases / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D015536:Down-Regulation / Q000235:genetics; D058851:GPI-Linked Proteins / Q000378:metabolism; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D018259:Herpesvirus 1, Human / Q000235:genetics*; D006801:Humans; D057131:Immune Evasion; D007694:Killer Cells, Natural / Q000378:metabolism; D008024:Ligands; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D000217:Acyltransferases; D015703:Antigens, CD; D058851:GPI-Linked Proteins; D017261:Glycosylphosphatidylinositols; D008024:Ligands; D035683:MicroRNAs; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C081007:COOH-terminal signal transamidase
keywords: GPI anchoring; HSV1; NK cells; immune evasion; microRNA; tetherin