title: Host immune system gene targeting by a viral miRNA.
abstract: Virally encoded microRNAs (miRNAs) have recently been discovered in herpesviruses. However, their biological roles are mostly unknown. We developed an algorithm for the prediction of miRNA targets and applied it to human cytomegalovirus miRNAs, resulting in the identification of the major histocompatibility complex class I-related chain B (MICB) gene as a top candidate target of hcmv-miR-UL112. MICB is a stress-induced ligand of the natural killer (NK) cell activating receptor NKG2D and is critical for the NK cell killing of virus-infected cells and tumor cells. We show that hcmv-miR-UL112 specifically down-regulates MICB expression during viral infection, leading to decreased binding of NKG2D and reduced killing by NK cells. Our results reveal a miRNA-based immunoevasion mechanism that appears to be exploited by human cytomegalovirus.
authors.affiliation: Lautenberg Center for General and Tumor Immunology, Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: Noam
authors.initials: N
authors.lastname: Stern-Ginossar
authors.forename: Naama
authors.initials: N
authors.lastname: Elefant
authors.forename: Albert
authors.initials: A
authors.lastname: Zimmermann
authors.forename: Dana G
authors.initials: DG
authors.lastname: Wolf
authors.forename: Nivin
authors.initials: N
authors.lastname: Saleh
authors.forename: Moshe
authors.initials: M
authors.lastname: Biton
authors.forename: Elad
authors.initials: E
authors.lastname: Horwitz
authors.forename: Zafnat
authors.initials: Z
authors.lastname: Prokocimer
authors.forename: Mark
authors.initials: M
authors.lastname: Prichard
authors.forename: Gabriele
authors.initials: G
authors.lastname: Hahn
authors.forename: Debra
authors.initials: D
authors.lastname: Goldman-Wohl
authors.forename: Caryn
authors.initials: C
authors.lastname: Greenfield
authors.forename: Simcha
authors.initials: S
authors.lastname: Yagel
authors.forename: Hartmut
authors.initials: H
authors.lastname: Hengel
authors.forename: Yael
authors.initials: Y
authors.lastname: Altuvia
authors.forename: Hanah
authors.initials: H
authors.lastname: Margalit
authors.forename: Ofer
authors.initials: O
authors.lastname: Mandelboim
mesh_terms: D020413:3' Untranslated Regions / Q000378:metabolism; D000465:Algorithms; D001665:Binding Sites; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D003602:Cytotoxicity, Immunologic; D015536:Down-Regulation; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008024:Ligands; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D055655:NK Cell Lectin-Like Receptor Subfamily K; D012367:RNA, Viral / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism; D055607:Receptors, Natural Killer Cell; D014161:Transduction, Genetic
chemical_list: D020413:3' Untranslated Regions; D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; D008024:Ligands; C099187:MHC class I-related chain A; C098080:MICB antigen; D035683:MicroRNAs; D055655:NK Cell Lectin-Like Receptor Subfamily K; D012367:RNA, Viral; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell