Evidence map›Paper›PMID 26667483›Full record

ArticleRetrovirology2015

Phosphorylation of murine SAMHD1 regulates its antiretroviral activity.

Sabine Wittmann, Rayk Behrendt, Kristin Eissmann, Bianca Volkmann, Dominique Thomas, Thomas Ebert, Alexandra Cribier, Monsef Benkirane, Veit Hornung, Nerea Ferreirós Bouzas and 1 more

Open access · goldAbstract read
In one paragraph

Article in Retrovirology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
3.5field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 65 citations in OpenAlex.

  1. Article
  2. SAMHD1 restricts the deoxyguanosine triphosphate pool contributing to telomere stability in telomerase-positive cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023
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  14. μ-Lat: A mouse model to evaluate human immunodeficiency virus eradication strategies.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020
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  19. Positive selection in dNTPase SAMHD1 throughout mammalian evolution.Proceedings of the National Academy of Sciences of the United States of America · 2019
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 7 institutions in 2 countries.

Sabine WittmannInstitute of Clinical and Molecular Virology, Friedrich-Alexander University Erlangen-Nürnberg, Schlossgarten 4, 91054, Erlangen, Germany. sabine.wittmann@viro.med.uni-erlangen.de.
Rayk BehrendtInstitute for Immunology, Medical Faculty Carl Gustav Carus, University of Technology Dresden, Fetscherstrasse 74, 01307, Dresden, Germany. Rayk.Behrendt@tu-dresden.de.
Kristin EissmannInstitute of Clinical and Molecular Virology, Friedrich-Alexander University Erlangen-Nürnberg, Schlossgarten 4, 91054, Erlangen, Germany. kristin.eissmann@viro.med.uni-erlangen.de.
Bianca VolkmannInstitute of Clinical and Molecular Virology, Friedrich-Alexander University Erlangen-Nürnberg, Schlossgarten 4, 91054, Erlangen, Germany. bianca.volkmann@viro.med.uni-erlangen.de.
Dominique ThomasPharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe-University, Frankfurt Theodor Stern Kai 7, 60590, Frankfurt am Main, Germany. Thomas@med.uni-frankfurt.de.
Thomas EbertInstitute of Molecular Medicine, University Hospital, University of Bonn, Bonn, Germany. ebert1987@gmail.com.
Alexandra CribierLaboratoire de Virologie Moléculaire, Institut de Génétique Humaine, CNRS UPR1142, Montpellier, 34000, France. alexandra.cribier@igh.cnrs.fr.
Monsef BenkiraneLaboratoire de Virologie Moléculaire, Institut de Génétique Humaine, CNRS UPR1142, Montpellier, 34000, France. monsef.benkirane@igh.cnrs.fr.
Veit HornungInstitute of Molecular Medicine, University Hospital, University of Bonn, Bonn, Germany. veit.hornung@uni-bonn.de.
Nerea Ferreirós BouzasPharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe-University, Frankfurt Theodor Stern Kai 7, 60590, Frankfurt am Main, Germany. ferreirosbouzas@em.uni-frankfurt.de.
Thomas GrambergInstitute of Clinical and Molecular Virology, Friedrich-Alexander University Erlangen-Nürnberg, Schlossgarten 4, 91054, Erlangen, Germany. thomas.gramberg@viro.med.uni-erlangen.de.
Friedrich-Alexander-Universität Erlangen-Nürnberg · DEGoethe University Frankfurt · DEInstitut de Génétique Humaine · FRInstitut de Génétique Moléculaire de Montpellier · FRUniversity Hospital Bonn · DEUniversity Hospital Carl Gustav Carus · DEUniversity of Bonn · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHuman SAMHD1 is a triphosphohydrolase that restricts the replication of retroviruses, retroelements and DNA viruses in noncycling cells. While modes of action have been extensively described for human SAMHD1, only little is known about the regulation of SAMHD1 in the mouse. Here, we characterize the antiviral activity of murine SAMHD1 with the help of knockout mice to shed light on the regulation and the mechanism of the SAMHD1 restriction and to validate the SAMHD1 knockout mouse model for the use in future infectivity studies.

resultsWe found that endogenous mouse SAMHD1 restricts not only HIV-1 but also MLV reporter virus infection at the level of reverse transcription in primary myeloid cells. Similar to the human protein, the antiviral activity of murine SAMHD1 is regulated through phosphorylation at threonine 603 and is limited to nondividing cells. Comparing the susceptibility to infection with intracellular dNTP levels and SAMHD1 phosphorylation in different cell types shows that both functions are important determinants of the antiviral activity of murine SAMHD1. In contrast, we found the proposed RNase activity of SAMHD1 to be less important and could not detect any effect of mouse or human SAMHD1 on the level of incoming viral RNA.

conclusionOur findings show that SAMHD1 in the mouse blocks retroviral infection at the level of reverse transcription and is regulated through cell cycle-dependent phosphorylation. We show that the antiviral restriction mediated by murine SAMHD1 is mechanistically similar to what is known for the human protein, making the SAMHD1 knockout mouse model a valuable tool to characterize the influence of SAMHD1 on the replication of different viruses in vivo.

Indexed as

Reverse TranscriptionAnimalsCell LineCells, CulturedHIV-1HumansLeukemia Virus, MurineMacrophagesMiceMice, KnockoutMonomeric GTP-Binding ProteinsMyeloid CellsPhosphorylationRetroviridae InfectionsRNA, ViralSAM Domain and HD Domain-Containing Protein 1Monomeric GTP-Binding ProteinsRNA, ViralSAM Domain and HD Domain-Containing Protein 1Samhd1 protein, mouseThreonine

Identifiers

PMID26667483
PMCPMC4678485
OpenAlexW2204308538

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.