Mouse SAMHD1 Has Antiretroviral Activity and Suppresses a Spontaneous Cell-Intrinsic Antiviral Response.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Nguyen, Laura A
MetadataShow full item record
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.
CitationMouse SAMHD1 Has Antiretroviral Activity and Suppresses a Spontaneous Cell-Intrinsic Antiviral Response. 2013, 4 (4):689-96 Cell Rep
AffiliationInstitute for Immunology, Medical Faculty Carl Gustav Carus, University of Technology Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
The following license files are associated with this item:
- SAMHD1 restricts HIV-1 infection in dendritic cells (DCs) by dNTP depletion, but its expression in DCs and primary CD4+ T-lymphocytes cannot be upregulated by interferons.
- Authors: St Gelais C, de Silva S, Amie SM, Coleman CM, Hoy H, Hollenbaugh JA, Kim B, Wu L
- Issue date: 2012 Dec 11
- Phosphorylation of murine SAMHD1 regulates its antiretroviral activity.
- Authors: Wittmann S, Behrendt R, Eissmann K, Volkmann B, Thomas D, Ebert T, Cribier A, Benkirane M, Hornung V, Bouzas NF, Gramberg T
- Issue date: 2015 Dec 15
- HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase.
- Authors: Goldstone DC, Ennis-Adeniran V, Hedden JJ, Groom HC, Rice GI, Christodoulou E, Walker PA, Kelly G, Haire LF, Yap MW, de Carvalho LP, Stoye JP, Crow YJ, Taylor IA, Webb M
- Issue date: 2011 Nov 6
- SAMHD1: a novel antiviral factor in intrinsic immunity.
- Authors: Chen Z, Zhang L, Ying S
- Issue date: 2012 Sep
- SAMHD1 prevents autoimmunity by maintaining genome stability.
- Authors: Kretschmer S, Wolf C, König N, Staroske W, Guck J, Häusler M, Luksch H, Nguyen LA, Kim B, Alexopoulou D, Dahl A, Rapp A, Cardoso MC, Shevchenko A, Lee-Kirsch MA
- Issue date: 2015 Mar