Evidence map›Paper›PMID 41297541›Full record

ArticleCell host & microbe2025

Divergent viral phosphodiesterases for immune signaling evasion.

Erin E Doherty, Jason Nomburg, Benjamin A Adler, Santiago Lopez, Kendall Hsieh, Nathan Price, Nurashau Blount, Jennifer A Doudna

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell host & microbe, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. A Novel Lytic Podovirus AP-20-A InfectingInternational journal of molecular sciences · 2026
    Article
  3. Phage RyR-domain proteins degrade ADPR-based immune signals and fuel NADbioRxiv : the preprint server for biology · 2026
    Article
  4. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Erin E DohertyInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA 94720, USA.
Jason NomburgInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Gladstone Institutes, University of California, San Francisco, San Francisco, CA 94114, USA.
Benjamin A AdlerInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA 94720, USA.
Santiago LopezInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA 94720, USA.
Kendall HsiehDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Nathan PriceInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Gladstone Institutes, University of California, San Francisco, San Francisco, CA 94114, USA.
Nurashau BlountInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Jennifer A DoudnaInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA 94720, USA; Gladstone Institutes, University of California, San Francisco, San Francisco, CA 94114, USA; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Chemistry, University of California, Berkeley, Berkeley, CA, USA; MBIB Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address: doudna@berkeley.edu.

Funding

A Synchrotron Radiation Structural Biology ResourcesP30GM133894 · NIGMS · STANFORD UNIVERSITY · PI Thomas Michael Weiss · 2020 to 2026
$43.3M
High Definition Ion Mobility SpectrometerS10OD020062 · OD · UNIVERSITY OF CALIFORNIA BERKELEY · PI WILLIAMS, EVAN R · 2015 to 2015
$590k
Precision Deaminases to Expand the Scope of Diseases Amenable to CRISPR-mediated CorrectionF32GM153031 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI Erin Doherty Blackett · 2024 to 2026
$229k
Site-directed RNA Editing to Modulate Kinase Activity as a ChemotherapeuticF31CA265135 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI DOHERTY, ERIN E · 2021 to 2021
$38k
NCI NIH HHS F31 CA265135NIGMS NIH HHS F32 GM153031NIGMS NIH HHS P30 GM133894NIH HHS S10 OD020062
6 · The paper itself

Abstract

Cyclic dinucleotides (CDNs) and other short oligonucleotides play fundamental roles in immune system activation in organisms ranging from bacteria to humans. In response, viruses use phosphodiesterase (PDE)-mediated oligonucleotide cleavage for immune evasion, a strategy whose diversity has not yet been explored. Here, we use a canonical 2H PDE (2H PDE) structure-based search of prokaryotic and eukaryotic viral sequences to identify an exceptional diversity of 2H PDEs across the virome, including enzymes not detectable with sequence search methods alone. Despite active site conservation, biochemical experiments reveal remarkable substrate specificity of these PDEs that corresponds to variations in the core 2H fold. This nuanced specificity allows 2H PDEs to selectively degrade oligonucleotide messengers to avoid interfering with host nucleotide signaling. Together, these findings nominate viral 2H PDEs as key regulators of CDN signaling across the tree of life.

Indexed as

Immune EvasionPhosphoric Diester HydrolasesSignal TransductionViral ProteinsVirusesCatalytic DomainHumansSubstrate SpecificityPhosphoric Diester HydrolasesViral Proteinsanti-viral immunityCBASSCD-NTasescGAMPcGAS-STINGimmune evasionoligonucleotide messengersphosphodiesterasesstructure-based searchX-ray crystallography

Identifiers

PMID41297541
PMCPMC12730640

What OpenQuestion holds

Textmetadata
LicenceTDM
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.