Mouse SAMHD1 Has Antiretroviral Activity and Suppresses a Spontaneous Cell-Intrinsic Antiviral Response.
dc.contributor.author | Behrendt, Rayk | |
dc.contributor.author | Schumann, Tina | |
dc.contributor.author | Gerbaulet, Alexander | |
dc.contributor.author | Nguyen, Laura A | |
dc.contributor.author | Schubert, Nadja | |
dc.contributor.author | Alexopoulou, Dimitra | |
dc.contributor.author | Berka, Ursula | |
dc.contributor.author | Lienenklaus, Stefan | |
dc.contributor.author | Peschke, Katrin | |
dc.contributor.author | Gibbert, Kathrin | |
dc.contributor.author | Wittmann, Sabine | |
dc.contributor.author | Lindemann, Dirk | |
dc.contributor.author | Weiss, Siegfried | |
dc.contributor.author | Dahl, Andreas | |
dc.contributor.author | Naumann, Ronald | |
dc.contributor.author | Dittmer, Ulf | |
dc.contributor.author | Kim, Baek | |
dc.contributor.author | Mueller, Werner | |
dc.contributor.author | Gramberg, Thomas | |
dc.contributor.author | Roers, Axel | |
dc.date.accessioned | 2013-10-09T10:51:19Z | |
dc.date.available | 2013-10-09T10:51:19Z | |
dc.date.issued | 2013-08-29 | |
dc.identifier.citation | Mouse SAMHD1 Has Antiretroviral Activity and Suppresses a Spontaneous Cell-Intrinsic Antiviral Response. 2013, 4 (4):689-96 Cell Rep | en |
dc.identifier.issn | 2211-1247 | |
dc.identifier.pmid | 23972988 | |
dc.identifier.doi | 10.1016/j.celrep.2013.07.037 | |
dc.identifier.uri | http://hdl.handle.net/10033/303064 | |
dc.description.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. | |
dc.language.iso | en | en |
dc.rights | Archived with thanks to Cell reports | en |
dc.title | Mouse SAMHD1 Has Antiretroviral Activity and Suppresses a Spontaneous Cell-Intrinsic Antiviral Response. | en |
dc.type | Article | en |
dc.contributor.department | Institute for Immunology, Medical Faculty Carl Gustav Carus, University of Technology Dresden, Fetscherstrasse 74, 01307 Dresden, Germany. | en |
dc.identifier.journal | Cell reports | en |
refterms.dateFOA | 2018-06-12T21:39:42Z | |
html.description.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. |