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

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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4807655/
https://www.ncbi.nlm.nih.gov/pubmed/23972988
http://dx.doi.org/10.1016/j.celrep.2013.07.037
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author 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
author_facet 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
author_sort Behrendt, Rayk
collection PubMed
description 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 deoxy-nucleotide (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.
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spelling pubmed-48076552016-03-25 Mouse SAMHD1 Has Antiretroviral Activity and Suppresses a Spontaneous Cell-Intrinsic Antiviral Response 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 Cell Rep Article 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 deoxy-nucleotide (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. 2013-08-22 2013-08-29 /pmc/articles/PMC4807655/ /pubmed/23972988 http://dx.doi.org/10.1016/j.celrep.2013.07.037 Text en http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
spellingShingle Article
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
Mouse SAMHD1 Has Antiretroviral Activity and Suppresses a Spontaneous Cell-Intrinsic Antiviral Response
title Mouse SAMHD1 Has Antiretroviral Activity and Suppresses a Spontaneous Cell-Intrinsic Antiviral Response
title_full Mouse SAMHD1 Has Antiretroviral Activity and Suppresses a Spontaneous Cell-Intrinsic Antiviral Response
title_fullStr Mouse SAMHD1 Has Antiretroviral Activity and Suppresses a Spontaneous Cell-Intrinsic Antiviral Response
title_full_unstemmed Mouse SAMHD1 Has Antiretroviral Activity and Suppresses a Spontaneous Cell-Intrinsic Antiviral Response
title_short Mouse SAMHD1 Has Antiretroviral Activity and Suppresses a Spontaneous Cell-Intrinsic Antiviral Response
title_sort mouse samhd1 has antiretroviral activity and suppresses a spontaneous cell-intrinsic antiviral response
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4807655/
https://www.ncbi.nlm.nih.gov/pubmed/23972988
http://dx.doi.org/10.1016/j.celrep.2013.07.037
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