Mouse SAMHD1 has antiretroviral activity and suppresses a spontaneous cell-intrinsic antiviral response
Publikation: Beitrag in Fachzeitschrift › Forschungsartikel › Beigetragen › Begutachtung
Beitragende
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.
Details
Originalsprache | Englisch |
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Seiten (von - bis) | 689-696 |
Seitenumfang | 8 |
Fachzeitschrift | Cell reports |
Jahrgang | 4 |
Ausgabenummer | 4 |
Publikationsstatus | Veröffentlicht - 29 Aug. 2013 |
Peer-Review-Status | Ja |
Externe IDs
PubMedCentral | PMC4807655 |
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ORCID | /0000-0002-0320-4223/work/150885032 |
Scopus | 84883277795 |
Schlagworte
Schlagwörter
- Animals, Dendritic Cells/metabolism, Deoxyribonucleotides/metabolism, Friend murine leukemia virus/metabolism, HIV-1/metabolism, Interferon-beta/genetics, Lymphocytes/metabolism, Macrophages/metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Monomeric GTP-Binding Proteins/genetics, Receptor, Interferon alpha-beta/genetics, Reverse Transcription, SAM Domain and HD Domain-Containing Protein 1, Transcription, Genetic, Up-Regulation, Virus Replication