Evidence map›Paper›PMID 40424128›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2025

Alternative cGAS signaling promotes herpes simplex encephalitis.

Liraz Shmuel-Galia, Zhaozhao Jiang, Laurel Stine, Sara Cahill, Sze-Ling Ng, Ruth Wilson, Richard Kumaran Kandasamy, Evelyn A Kurt-Jones, Joshi M Ramanjulu, John Bertin and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

14 authors.

Liraz Shmuel-GaliaDivision of Innate Immunity, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605.
Zhaozhao JiangDivision of Innate Immunity, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605.ORCID 0000-0002-9768-8491
Laurel StineDivision of Innate Immunity, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605.
Sara CahillDivision of Innate Immunity, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605.
Sze-Ling NgInnate Immunity Research Unit, GlaxoSmithKline, Collegeville, PA 19426.
Ruth WilsonDivision of Innate Immunity, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605.
Richard Kumaran KandasamyCentre of Molecular Inflammation Research, and Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim 7491, Norway.
Evelyn A Kurt-JonesDivision of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Chan Medical, Worcester, MA 01605.
Joshi M RamanjuluInnate Immunity Research Unit, GlaxoSmithKline, Collegeville, PA 19426.
John BertinImmunology and Inflammation Therapeutic Area, Sanofi, Cambridge, MA 02139.
Viera KasparcovaInnate Immunity Research Unit, GlaxoSmithKline, Collegeville, PA 19426.
G Scott Pesiridis *Innate Immunity Research Unit, GlaxoSmithKline, Collegeville, PA 19426.ORCID 0000-0003-1315-6453
Katherine A Fitzgerald *Division of Innate Immunity, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605.ORCID 0000-0003-3175-609X
Fiachra Humphries *Division of Innate Immunity, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605.

Funding

Innate Immunity Training ProgramT32AI095213 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI SILVERMAN, NEAL · 2011 to 2025
$2.5M
Charles H. Hood Foundation (CHF) Child Health AwardCrohn's and Colitis Foundation (CCF) Development AwardHHS | NIH | NIAID | Division of Microbiology and Infectious Diseases (DMID) R01NIAID NIH HHS T32 AI095213
6 · The paper itself

Abstract

During infection, foreign DNA is sensed by cyclic GMP-AMP synthase (cGAS) leading to the production of cGAMP, STING-dependent type I interferon and proinflammatory cytokine expression, and autophagy. To prevent a response to self-DNA, cGAS activity is tightly regulated. Dysregulation of cGAS underpins interferonopathies, such as Aicardi-Goutières syndrome, as well as Lupus and neurodegenerative diseases like Parkinson's disease. Thus, cGAS and its product cGAMP are therapeutic targets. However, if cGAS functions independently of cGAMP signaling is undefined. Here, we identified an alternative signaling pathway that cGAS engages independent of cGAMP synthesis. We demonstrate that alternative cGAS signaling promotes hyperexpression of CXCL1 and enhanced neutrophil recruitment that facilitates viral dissemination during herpes simplex encephalitis. Our study reports of an alternative cGAS response independent of cGAMP, highlighting a previously uncharacterized scaffold function for cGAS.

Indexed as

Encephalitis, Herpes SimplexNucleotidyltransferasesSignal TransductionAnimalsCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseHerpesvirus 1, HumanHumansMiceMice, Inbred C57BLNucleotides, CycliccGAS protein, humancGAS protein, mousecyclic guanosine monophosphate-adenosine monophosphateCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseNucleotides, CyclicNucleotidyltransferasescGASHSVinfectionmouse modeltype I IFN

Identifiers

PMID40424128
PMCPMC12146762

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.