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

Behrendt R, Schumann T, Gerbaulet A, Nguyen LA, Schubert N, Alexopoulou D, Berka U, Lienenklaus S, Peschke K, Gibbert K, Wittmann S, Lindemann D, Weiss S, Dahl A, Naumann R, Dittmer U, Kim B, Mueller W, Gramberg T, Roers A (2013)

Publication Type: Journal article

Publication year: 2013

Journal

Cell Reports Elsevier (Cell Press)

Book Volume: 4

Pages Range: 689-696

Journal Issue: 4

DOI: 10.1016/j.celrep.2013.07.037

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

Authors with CRIS profile

Sabine Wittmann Institute of Clinical and Molecular Virology Thomas Gramberg Institute of Clinical and Molecular Virology

Involved external institutions

Universitätsklinikum Essen DE Germany (DE) Universitätsklinikum Carl Gustav Carus Dresden DE Germany (DE) Helmholtz-Zentrum für Infektionsforschung (HZI) DE Germany (DE) DFG Center for Regenerative Therapies Dresden (CRTD) / DFG-Forschungszentrum für regenerative Therapien Dresden DE Germany (DE) University of Rochester Medical Center Rochester, NY US United States (USA) (US) Max-Planck-Institut für molekulare Zellbiologie und Genetik / Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) DE Germany (DE) University of Manchester GB United Kingdom (GB) Kyung Hee University KR Korea, Republic of (KR)

How to cite

APA:

Behrendt, R., Schumann, T., Gerbaulet, A., Nguyen, L.A., Schubert, N., Alexopoulou, D.,... Roers, A. (2013). Mouse SAMHD1 has antiretroviral activity and suppresses a spontaneous cell-intrinsic antiviral response. Cell Reports, 4(4), 689-696. https://doi.org/10.1016/j.celrep.2013.07.037

MLA:

Behrendt, Rayk, et al. "Mouse SAMHD1 has antiretroviral activity and suppresses a spontaneous cell-intrinsic antiviral response." Cell Reports 4.4 (2013): 689-696.

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