Mouse SAMHD1 has antiretroviral activity and suppresses a spontaneous cell-intrinsic antiviral response

Research output: Contribution to journalArticle

  • External authors:
  • Rayk Behrendt
  • Tina Schumann
  • Alexander Gerbaulet
  • Laura A. Nguyen
  • Nadja Schubert
  • Dimitra Alexopoulou
  • Ursula Berka
  • Stefan Lienenklaus
  • Katrin Peschke
  • Kathrin Gibbert
  • Sabine Wittmann
  • Dirk Lindemann
  • Siegfried Weiss
  • Andreas Dahl
  • Ronald Naumann
  • Ulf Dittmer
  • Baek Kim
  • Thomas Gramberg
  • Axel Roers

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 bydefects of SAMHD1, a 3@ exonuclease and deoxynucleotide (dNTP) triphosphohydrolase. Human SAMHD1 is an HIV-1 restriction factor that hydrolyzes dNTPs and decreases their concentrationbelow 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

Bibliographical metadata

Original languageEnglish
Pages (from-to)689-696
Number of pages7
JournalCell Reports
Volume4
Issue number4
DOIs
Publication statusPublished - 29 Aug 2013