title: HIV Triggers a cGAS-Dependent, Vpu- and Vpr-Regulated Type I Interferon Response in CD4+T Cells.
abstract: Several pattern-recognition receptors sense HIV-1 replication products and induce type I interferon (IFN-I) production under specific experimental conditions. However, it is thought that viral sensing and IFN induction are virtually absent in the main target cells of HIV-1 in vivo. Here, we show that activated CD4+T cells sense HIV-1 infection through the cytosolic DNA sensor cGAS and mount a bioactive IFN-I response. Efficient induction of IFN-I by HIV-1 infection requires proviral integration and is regulated by newly expressed viral accessory proteins: Vpr potentiates, while Vpu suppresses cGAS-dependent IFN-I induction. Furthermore, Vpr also amplifies innate sensing of HIV-1 infection in Vpx-treated dendritic cells. Our results identify cGAS as mediator of an IFN-I response to HIV-1 infection in CD4+T cells and demonstrate that this response is modulated by the viral accessory proteins Vpr and Vpu. Thus, viral innate immune evasion is incomplete in the main target cells of HIV-1.
authors.affiliation: Department of Clinical Chemistry, Microbiology, and Immunology, Ghent University, 9000 Ghent, Belgium.
authors.forename: Jolien
authors.initials: J
authors.lastname: Vermeire
authors.affiliation: Département de Virologie, Unité Virus et Immunité, Institut Pasteur, 75015 Paris, France.
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Roesch
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sauter
authors.affiliation: Département de Virologie, Unité Virus et Immunité, Institut Pasteur, 75015 Paris, France.
authors.forename: Réjane
authors.initials: R
authors.lastname: Rua
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Hotter
authors.affiliation: Department of Clinical Chemistry, Microbiology, and Immunology, Ghent University, 9000 Ghent, Belgium.
authors.forename: Anouk
authors.initials: A
authors.lastname: Van Nuffel
authors.affiliation: Department of Clinical Chemistry, Microbiology, and Immunology, Ghent University, 9000 Ghent, Belgium.
authors.forename: Hanne
authors.initials: H
authors.lastname: Vanderstraeten
authors.affiliation: Department of Clinical Chemistry, Microbiology, and Immunology, Ghent University, 9000 Ghent, Belgium.
authors.forename: Evelien
authors.initials: E
authors.lastname: Naessens
authors.affiliation: Department of Clinical Chemistry, Microbiology, and Immunology, Ghent University, 9000 Ghent, Belgium.
authors.forename: Veronica
authors.initials: V
authors.lastname: Iannucci
authors.affiliation: Department of Clinical Chemistry, Microbiology, and Immunology, Ghent University, 9000 Ghent, Belgium.
authors.forename: Alessia
authors.initials: A
authors.lastname: Landi
authors.affiliation: Department of Clinical Chemistry, Microbiology, and Immunology, Ghent University, 9000 Ghent, Belgium.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Witkowski
authors.affiliation: Department of Clinical Chemistry, Microbiology, and Immunology, Ghent University, 9000 Ghent, Belgium.
authors.forename: Ann
authors.initials: A
authors.lastname: Baeyens
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Kirchhoff
authors.affiliation: Department of Clinical Chemistry, Microbiology, and Immunology, Ghent University, 9000 Ghent, Belgium. Electronic address: bruno.verhasselt@ugent.be.
authors.forename: Bruno
authors.initials: B
authors.lastname: Verhasselt
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D057809:HEK293 Cells; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity; D054298:Human Immunodeficiency Virus Proteins / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology*; D016086:Lentivirus / Q000235:genetics; D009713:Nucleotidyltransferases / Q000235:genetics* / Q000276:immunology; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics* / Q000276:immunology; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000235:genetics* / Q000276:immunology; D000086082:Viroporin Proteins; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase
chemical_list: D054298:Human Immunodeficiency Virus Proteins; D007370:Interferon Type I; D009713:Nucleotidyltransferases; D054334:Viral Regulatory and Accessory Proteins; D054325:vpr Gene Products, Human Immunodeficiency Virus; C514912:vpr protein, Human immunodeficiency virus 1; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins; C578390:cGAS protein, human; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase
keywords: CD4; HIV; NF-κB; T cells; Vpr; Vpu; cGAS; dendritic cells; innate sensing; interferon