Evidence map›Paper›PMID 41880208›Full record

ArticleThe Journal of general virology2026

SARS-CoV-2 Nsp15 facilitates immune evasion and viral replication by limiting multiple host innate immune pathways, including cGAS-STING.

Hsin-Ping Chiu, Yao Yu Yeo, Tsoi Ying Lai, Chuan-Tien Hung, Shreyas Kowdle, Griffin D Haas, Sizun Jiang, Weina Sun, Benhur Lee

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of general virology, 2026. 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

9 authors.

Hsin-Ping ChiuDepartment of Microbiology, Icahn School of Medicine, Mount Sinai, New York, NY, USA.
Yao Yu YeoCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Tsoi Ying LaiDepartment of Microbiology, Icahn School of Medicine, Mount Sinai, New York, NY, USA.
Chuan-Tien HungDepartment of Microbiology, Icahn School of Medicine, Mount Sinai, New York, NY, USA.
Shreyas KowdleDepartment of Microbiology, Icahn School of Medicine, Mount Sinai, New York, NY, USA.
Griffin D HaasDepartment of Microbiology, Icahn School of Medicine, Mount Sinai, New York, NY, USA.
Sizun JiangCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Weina SunDepartment of Microbiology, Icahn School of Medicine, Mount Sinai, New York, NY, USA.
Benhur LeeDepartment of Microbiology, Icahn School of Medicine, Mount Sinai, New York, NY, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nonstructural protein 15 (Nsp15) is a conserved uridine-specific endoribonuclease (EndoU) and is implicated in innate immune evasion, yet its precise molecular mechanism remains incompletely understood. Here, we demonstrate that Nsp15 limits antiviral innate immune responses in part by downregulating the cGAS-STING pathway. To investigate how Nsp15 antagonizes host innate immune responses, we engineered recombinant SARS-CoV-2 bearing WT or EndoU-inactive Nsp15 (H234A). Compared with the WT virus, the Nsp15-H234A mutant exhibited a 2-log decrease in peak viral titres in interferon (IFN)-competent A549-ACE2 cells, but not in their STAT1 knockout counterparts. This attenuation was partially reversed by STING knockout or STING inhibitors, highlighting STING's involvement in Nsp15-driven immune evasion. Transcriptomic analyses revealed the upregulation of IFNs and IFN-stimulated genes in cells infected with the Nsp15-H234A mutant virus. Notably, cGAS and STING transcripts and proteins were suppressed during WT but not mutant virus infections - even in STAT1-deficient cells - suggesting that Nsp15 contributes directly to their downregulation.

Indexed as

COVID-19Immune EvasionImmunity, InnateMembrane ProteinsNucleotidyltransferasesSARS-CoV-2Viral Nonstructural ProteinsVirus ReplicationA549 CellsAnimalscGAS-STING Signaling PathwayChlorocebus aethiopsCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseHumansSignal TransductionSTAT1 Transcription FactorcGAS protein, humanCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseMembrane ProteinsNucleotidyltransferasesSTAT1 Transcription FactorSTING1 protein, humanSTING ProteinViral Nonstructural ProteinscGAS-STINGendoribonucleaseinnate immune evasionNsp15severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Identifiers

PMID41880208
PMCPMC13016584

What Socratic holds

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LicenceCC BY
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Registered trials

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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 Socratic graph.