Evidence map›Paper›PMID 26343537›Full record

ArticleNature immunology2015

Sequence-specific activation of the DNA sensor cGAS by Y-form DNA structures as found in primary HIV-1 cDNA.

Anna-Maria Herzner, Cristina Amparo Hagmann, Marion Goldeck, Steven Wolter, Kirsten Kübler, Sabine Wittmann, Thomas Gramberg, Liudmila Andreeva, Karl-Peter Hopfner, Christina Mertens and 11 more

Open access · greenAbstract read
In one paragraph

Article in Nature immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 168 papers.

0numbers the graph read from it
0cells of the map it votes in
168citing papers in PubMed
11.3field-weighted citation impact, top 1% 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

168 citing papers in PubMed, 246 citations in OpenAlex.

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108 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors at 8 institutions in 3 countries.

Anna-Maria HerznerInstitute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany.
Cristina Amparo HagmannInstitute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany.
Marion GoldeckInstitute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany.
Steven WolterInstitute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany.
Kirsten KüblerDepartment of Obstetrics and Gynecology, Center for Integrated Oncology, University of Bonn, Bonn, Germany.
Sabine WittmannInstitute of Clinical and Molecular Virology, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
Thomas GrambergInstitute of Clinical and Molecular Virology, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
Liudmila AndreevaDepartment Biochemistry, Gene Center, Ludwig-Maximilians University, Munich, Germany.
Karl-Peter HopfnerDepartment Biochemistry, Gene Center, Ludwig-Maximilians University, Munich, Germany.
Christina MertensInstitute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany.
Thomas ZillingerInstitute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany.
Tengchuan JinSchool of Life Sciences, University of Science and Technology of China, Hefei, China.
Tsan Sam XiaoDepartment of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.ORCID http://orcid.org/0000-0001-9688-475X
Eva BartokInstitute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany.
Christoph CochInstitute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany.
Damian AckermannLIMES Institute, Chemical Biology, University of Bonn, Bonn, Germany.
Veit HornungInstitute of Molecular Medicine, University Hospital, University of Bonn, Bonn, Germany.
Janos LudwigInstitute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany.
Winfried BarchetInstitute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany.
Gunther HartmannInstitute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany.
Martin SchleeInstitute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany.ORCID http://orcid.org/0000-0003-3671-7639
University Hospital Bonn · DEBrigham and Women's Hospital · USFriedrich-Alexander-Universität Erlangen-Nürnberg · DEGerman Institute of Development and Sustainability · DELudwig-Maximilians-Universität München · DEUniversity of Bonn · DECase Western Reserve University · USUniversity of Science and Technology of China · CN

Funding

Intramural NIH HHS Z99 AI999999
6 · The paper itself

Abstract

Cytosolic DNA that emerges during infection with a retrovirus or DNA virus triggers antiviral type I interferon responses. So far, only double-stranded DNA (dsDNA) over 40 base pairs (bp) in length has been considered immunostimulatory. Here we found that unpaired DNA nucleotides flanking short base-paired DNA stretches, as in stem-loop structures of single-stranded DNA (ssDNA) derived from human immunodeficiency virus type 1 (HIV-1), activated the type I interferon-inducing DNA sensor cGAS in a sequence-dependent manner. DNA structures containing unpaired guanosines flanking short (12- to 20-bp) dsDNA (Y-form DNA) were highly stimulatory and specifically enhanced the enzymatic activity of cGAS. Furthermore, we found that primary HIV-1 reverse transcripts represented the predominant viral cytosolic DNA species during early infection of macrophages and that these ssDNAs were highly immunostimulatory. Collectively, our study identifies unpaired guanosines in Y-form DNA as a highly active, minimal cGAS recognition motif that enables detection of HIV-1 ssDNA.

Indexed as

AnimalsCell LineCells, CulturedCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseDNA, ComplementaryDNA, ViralHEK293 CellsHIV-1HumansImmunizationInterferon-alphaMiceNucleotidyltransferasescGAS protein, mouseCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseDNA, ComplementaryDNA, ViralInterferon-alphaNucleotidyltransferases

Identifiers

PMID26343537
PMCPMC4669199
OpenAlexW2139936109

What OpenQuestion holds

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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.