title: ADAR1 Facilitates HIV-1 Replication in Primary CD4+ T Cells.
abstract: Unlike resting CD4+ T cells, activated CD4+T cells are highly susceptible to infection of human immunodeficiency virus 1 (HIV-1). HIV-1 infects T cells and macrophages without activating the nucleic acid sensors and the anti-viral type I interferon response. Adenosine deaminase acting on RNA 1 (ADAR1) is an RNA editing enzyme that displays antiviral activity against several RNA viruses. Mutations in ADAR1 cause the autoimmune disorder Aicardi-Goutieères syndrome (AGS). This disease is characterized by an inappropriate activation of the interferon-stimulated gene response. Here we show that HIV-1 replication, in ADAR1-deficient CD4+T lymphocytes from AGS patients, is blocked at the level of protein translation. Furthermore, viral protein synthesis block is accompanied by an activation of interferon-stimulated genes. RNA silencing of ADAR1 in Jurkat cells also inhibited HIV-1 protein synthesis. Our data support that HIV-1 requires ADAR1 for efficient replication in human CD4+T cells.
authors.affiliation: Department of Experimental Immunology, Academic Medical Center (AMC), University of Amsterdam (UvA), Amsterdam, The Netherlands.
authors.forename: Eloy
authors.initials: E
authors.lastname: Cuadrado
authors.affiliation: Department of Experimental Immunology, Academic Medical Center (AMC), University of Amsterdam (UvA), Amsterdam, The Netherlands.|Sanquin Research, Landsteiner Laboratory and Center for Infection and Immunity (CINIMA) at the Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Thijs
authors.initials: T
authors.lastname: Booiman
authors.affiliation: Department of Experimental Immunology, Academic Medical Center (AMC), University of Amsterdam (UvA), Amsterdam, The Netherlands.|Sanquin Research, Landsteiner Laboratory and Center for Infection and Immunity (CINIMA) at the Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: John L
authors.initials: JL
authors.lastname: van Hamme
authors.affiliation: Department of Experimental Immunology, Academic Medical Center (AMC), University of Amsterdam (UvA), Amsterdam, The Netherlands.
authors.forename: Machiel H
authors.initials: MH
authors.lastname: Jansen
authors.affiliation: Department of Experimental Immunology, Academic Medical Center (AMC), University of Amsterdam (UvA), Amsterdam, The Netherlands.|Sanquin Research, Landsteiner Laboratory and Center for Infection and Immunity (CINIMA) at the Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Karel A
authors.initials: KA
authors.lastname: van Dort
authors.affiliation: Center for Genetic Medicine Research, Children's National Medical Center, Washington DC, United States of America.
authors.forename: Adeline
authors.initials: A
authors.lastname: Vanderver
authors.affiliation: Manchester Centre for Genomic Medicine, University of Manchester, Manchester Academic Health Sciences Centre (MAHSC), Manchester, United Kingdom.
authors.forename: Gillian I
authors.initials: GI
authors.lastname: Rice
authors.affiliation: Manchester Centre for Genomic Medicine, University of Manchester, Manchester Academic Health Sciences Centre (MAHSC), Manchester, United Kingdom.|INSERM UMR 1163, Laboratory of Neurogenetics and Neuroinflammation, Institut Imagine, Hôpital Necker, Paris, France.
authors.forename: Yanick J
authors.initials: YJ
authors.lastname: Crow
authors.affiliation: Department of Experimental Immunology, Academic Medical Center (AMC), University of Amsterdam (UvA), Amsterdam, The Netherlands.|Sanquin Research, Landsteiner Laboratory and Center for Infection and Immunity (CINIMA) at the Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Neeltje A
authors.initials: NA
authors.lastname: Kootstra
authors.affiliation: Department of Experimental Immunology, Academic Medical Center (AMC), University of Amsterdam (UvA), Amsterdam, The Netherlands.|Emma Children's Hospital, Dept of Pediatric Hematology, Immunology and Infectious disease, AMC, UvA, Amsterdam, The Netherlands.
authors.forename: Taco W
authors.initials: TW
authors.lastname: Kuijpers
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics / Q000378:metabolism*; D000293:Adolescent; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000378:metabolism / Q000821:virology*; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D019169:Jurkat Cells; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014779:Virus Replication
chemical_list: D012333:RNA, Messenger; D012367:RNA, Viral; D016601:RNA-Binding Proteins; C000595356:ADAR protein, human; D000243:Adenosine Deaminase