Mouse SAMHD1 Has Antiretroviral Activity and Suppresses a Spontaneous Cell-Intrinsic Antiviral Response.

2.50
Hdl Handle:
http://hdl.handle.net/10033/303064
Title:
Mouse SAMHD1 Has Antiretroviral Activity and Suppresses a Spontaneous Cell-Intrinsic Antiviral Response.
Authors:
Behrendt, Rayk; Schumann, Tina; Gerbaulet, Alexander; Nguyen, Laura A; Schubert, Nadja; Alexopoulou, Dimitra; Berka, Ursula; Lienenklaus, Stefan; Peschke, Katrin; Gibbert, Kathrin; Wittmann, Sabine; Lindemann, Dirk; Weiss, Siegfried; Dahl, Andreas; Naumann, Ronald; Dittmer, Ulf; Kim, Baek; Mueller, Werner; Gramberg, Thomas; Roers, Axel
Abstract:
Aicardi-Goutières syndrome (AGS), a hereditary autoimmune disease, clinically and biochemically overlaps with systemic lupus erythematosus (SLE) and, like SLE, is characterized by spontaneous type I interferon (IFN) production. The finding that defects of intracellular nucleases cause AGS led to the concept that intracellular accumulation of nucleic acids triggers inappropriate production of type I IFN and autoimmunity. AGS can also be caused by defects of SAMHD1, a 3' exonuclease and deoxynucleotide (dNTP) triphosphohydrolase. Human SAMHD1 is an HIV-1 restriction factor that hydrolyzes dNTPs and decreases their concentration below the levels required for retroviral reverse transcription. We show in gene-targeted mice that also mouse SAMHD1 reduces cellular dNTP concentrations and restricts retroviral replication in lymphocytes, macrophages, and dendritic cells. Importantly, the absence of SAMHD1 triggered IFN-β-dependent transcriptional upregulation of type I IFN-inducible genes in various cell types indicative of spontaneous IFN production. SAMHD1-deficient mice may be instrumental for elucidating the mechanisms that trigger pathogenic type I IFN responses in AGS and SLE.
Affiliation:
Institute for Immunology, Medical Faculty Carl Gustav Carus, University of Technology Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
Citation:
Mouse SAMHD1 Has Antiretroviral Activity and Suppresses a Spontaneous Cell-Intrinsic Antiviral Response. 2013, 4 (4):689-96 Cell Rep
Journal:
Cell reports
Issue Date:
29-Aug-2013
URI:
http://hdl.handle.net/10033/303064
DOI:
10.1016/j.celrep.2013.07.037
PubMed ID:
23972988
Type:
Article
Language:
en
ISSN:
2211-1247
Appears in Collections:
publications of the research group molecular Immunology (MOLI)

Full metadata record

DC FieldValue Language
dc.contributor.authorBehrendt, Rayken
dc.contributor.authorSchumann, Tinaen
dc.contributor.authorGerbaulet, Alexanderen
dc.contributor.authorNguyen, Laura Aen
dc.contributor.authorSchubert, Nadjaen
dc.contributor.authorAlexopoulou, Dimitraen
dc.contributor.authorBerka, Ursulaen
dc.contributor.authorLienenklaus, Stefanen
dc.contributor.authorPeschke, Katrinen
dc.contributor.authorGibbert, Kathrinen
dc.contributor.authorWittmann, Sabineen
dc.contributor.authorLindemann, Dirken
dc.contributor.authorWeiss, Siegfrieden
dc.contributor.authorDahl, Andreasen
dc.contributor.authorNaumann, Ronalden
dc.contributor.authorDittmer, Ulfen
dc.contributor.authorKim, Baeken
dc.contributor.authorMueller, Werneren
dc.contributor.authorGramberg, Thomasen
dc.contributor.authorRoers, Axelen
dc.date.accessioned2013-10-09T10:51:19Z-
dc.date.available2013-10-09T10:51:19Z-
dc.date.issued2013-08-29-
dc.identifier.citationMouse SAMHD1 Has Antiretroviral Activity and Suppresses a Spontaneous Cell-Intrinsic Antiviral Response. 2013, 4 (4):689-96 Cell Repen
dc.identifier.issn2211-1247-
dc.identifier.pmid23972988-
dc.identifier.doi10.1016/j.celrep.2013.07.037-
dc.identifier.urihttp://hdl.handle.net/10033/303064-
dc.description.abstractAicardi-Goutières syndrome (AGS), a hereditary autoimmune disease, clinically and biochemically overlaps with systemic lupus erythematosus (SLE) and, like SLE, is characterized by spontaneous type I interferon (IFN) production. The finding that defects of intracellular nucleases cause AGS led to the concept that intracellular accumulation of nucleic acids triggers inappropriate production of type I IFN and autoimmunity. AGS can also be caused by defects of SAMHD1, a 3' exonuclease and deoxynucleotide (dNTP) triphosphohydrolase. Human SAMHD1 is an HIV-1 restriction factor that hydrolyzes dNTPs and decreases their concentration below the levels required for retroviral reverse transcription. We show in gene-targeted mice that also mouse SAMHD1 reduces cellular dNTP concentrations and restricts retroviral replication in lymphocytes, macrophages, and dendritic cells. Importantly, the absence of SAMHD1 triggered IFN-β-dependent transcriptional upregulation of type I IFN-inducible genes in various cell types indicative of spontaneous IFN production. SAMHD1-deficient mice may be instrumental for elucidating the mechanisms that trigger pathogenic type I IFN responses in AGS and SLE.en
dc.language.isoenen
dc.rightsArchived with thanks to Cell reportsen
dc.titleMouse SAMHD1 Has Antiretroviral Activity and Suppresses a Spontaneous Cell-Intrinsic Antiviral Response.en
dc.typeArticleen
dc.contributor.departmentInstitute for Immunology, Medical Faculty Carl Gustav Carus, University of Technology Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.en
dc.identifier.journalCell reportsen

Related articles on PubMed

This item is licensed under a Creative Commons License
Creative Commons
All Items in HZI are protected by copyright, with all rights reserved, unless otherwise indicated.