title: MicroRNA editing facilitates immune elimination of HCMV infected cells.
abstract: The human cytomegalovirus (HCMV) is extremely prevalent in the human population. Infection by HCMV is life threatening in immune compromised individuals and in immune competent individuals it can cause severe birth defects, developmental retardation and is even associated with tumor development. While numerous mechanisms were developed by HCMV to interfere with immune cell activity, much less is known about cellular mechanisms that operate in response to HCMV infection. Here we demonstrate that in response to HCMV infection, the expression of the short form of the RNA editing enzyme ADAR1 (ADAR1-p110) is induced. We identified the specific promoter region responsible for this induction and we show that ADAR1-p110 can edit miR-376a. Accordingly, we demonstrate that the levels of the edited-miR-376a (miR-376a(e)) increase during HCMV infection. Importantly, we show that miR-376a(e) downregulates the immune modulating molecule HLA-E and that this consequently renders HCMV infected cells susceptible to elimination by NK cells.
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute Israel Canada of the Faculty of Medicine, The Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: Daphna
authors.initials: D
authors.lastname: Nachmani
authors.affiliation: Department of Virology, Institute for Medical Microbiology and Hygiene, Albert-Ludwigs-Universitat, Freiburg, Germany.
authors.forename: Albert
authors.initials: A
authors.lastname: Zimmermann
authors.affiliation: Virology Unit, Hadassah Hospital, The Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: Esther
authors.initials: E
authors.lastname: Oiknine Djian
authors.affiliation: Virology Unit, Hadassah Hospital, The Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: Yiska
authors.initials: Y
authors.lastname: Weisblum
authors.affiliation: Department of Neurobiology, Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem, Israel.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Livneh
authors.affiliation: Institute for Virology of the University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Vu Thuy
authors.initials: VT
authors.lastname: Khanh Le
authors.affiliation: Goldyne Savad Institute of Gene Therapy, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Eithan
authors.initials: E
authors.lastname: Galun
authors.affiliation: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Vaclav
authors.initials: V
authors.lastname: Horejsi
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Isakov
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Noam
authors.initials: N
authors.lastname: Shomron
authors.affiliation: Virology Unit, Hadassah Hospital, The Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: Dana G
authors.initials: DG
authors.lastname: Wolf
authors.affiliation: Department of Virology, Institute for Medical Microbiology and Hygiene, Albert-Ludwigs-Universitat, Freiburg, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Hengel
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute Israel Canada of the Faculty of Medicine, The Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Mandelboim
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics*; D015153:Blotting, Western; D003587:Cytomegalovirus; D003586:Cytomegalovirus Infections / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D035683:MicroRNAs / Q000235:genetics*; D017393:RNA Editing / Q000235:genetics*; D016601:RNA-Binding Proteins
chemical_list: D035683:MicroRNAs; D016601:RNA-Binding Proteins; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase