Evidence map›Paper›PMID 40693792›Full record

ArticlemBio2025

ADAR1 haploinsufficiency and sustained picornaviral RdRp dsRNA synthesis synergize to dysregulate RNA editing and cause multi-system interferonopathy.

Caitlin M Miller, James H Morrison, Laura Bankers, Rachael Dran, Julia M Kendrick, Emma Briggs, Virginia L Ferguson, Eric M Poeschla

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in mBio, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Caitlin M Miller *Division of Infectious Diseases, Anschutz Medical Campus, University of Colorado School of Medicine, Aurora, Colorado, USA.
James H Morrison *Division of Infectious Diseases, Anschutz Medical Campus, University of Colorado School of Medicine, Aurora, Colorado, USA.ORCID 0000-0001-7385-5737
Laura BankersDivision of Infectious Diseases, Anschutz Medical Campus, University of Colorado School of Medicine, Aurora, Colorado, USA.
Rachael DranDivision of Infectious Diseases, Anschutz Medical Campus, University of Colorado School of Medicine, Aurora, Colorado, USA.
Julia M KendrickDivision of Infectious Diseases, Anschutz Medical Campus, University of Colorado School of Medicine, Aurora, Colorado, USA.
Emma BriggsDepartment of Mechanical Engineering and BioFrontiers Institute, University of Colorado at Boulder, Boulder, Colorado, USA.
Virginia L FergusonDepartment of Mechanical Engineering and BioFrontiers Institute, University of Colorado at Boulder, Boulder, Colorado, USA.
Eric M PoeschlaDivision of Infectious Diseases, Anschutz Medical Campus, University of Colorado School of Medicine, Aurora, Colorado, USA.ORCID 0000-0003-1598-5415

Funding

Novel Approaches to Innate Immunity Against HIV-1 and Other Co-infection VirusesDP1DA043915 · NIDA · UNIVERSITY OF COLORADO DENVER · PI POESCHLA, ERIC M. · 2017 to 2021
$3.9M
John H. Tietze Foundation Trust Innate ImmunityNational Science Foundation 1707065NIDA NIH HHS DP1 DA043915NIH HHS DP1DA043915
6 · The paper itself

Abstract

Sensing of viral double-stranded RNA (dsRNA) by MDA5 triggers abundant but transient interferon-stimulated gene (ISGs) expression. If dsRNA synthesis is made persistent by transgenically expressing a picornaviral RNA-dependent RNA polymerase (RdRp) in mice, lifelong MDA5-MAVS pathway activation and marked, global ISG upregulation result. This confers robust protection from viral diseases, but in contrast to numerous other chronic MDA5 hyperactivation states, the mice suffer no autoimmune or other health consequences. Here, we find that they further confound expectations by being resistant to a strong autoimmunity (lupus) provocation. However, knockout of one allele of IMPORTANCE: RNA virus double-stranded RNAs (dsRNAs) are important pathogen-associated molecular patterns that are sensed by the RIG-I-like receptor MDA5, which triggers an acute innate immune response involving many interferon-stimulated genes (ISGs). One key to a healthy innate immune system is that MDA5 does not sense endogenous dsRNA. This is normally ensured by dsRNA duplex-disrupting ADAR1 editing of host dsRNAs. Picornavirus RdRp

Indexed as

Adenosine DeaminaseHaploinsufficiencyInterferonsRNA-Binding ProteinsRNA-Dependent RNA PolymeraseRNA, Double-StrandedRNA EditingRNA, ViralAnimalsHumansInterferon-Induced Helicase, IFIH1MiceMice, KnockoutADAR1 protein, mouseAdenosine DeaminaseIfih1 protein, mouseInterferon-Induced Helicase, IFIH1InterferonsRNA-Binding ProteinsRNA-Dependent RNA PolymeraseRNA, Double-StrandedRNA, ViralADAR1autoimmunityautoinflammationinnate antiviral immunityinterferonopathylupusMDA5picornavirusRdRp

Identifiers

PMID40693792
PMCPMC12345148

What OpenQuestion holds

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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.