Evidence map›Paper›PMID 42139056›Full record

ArticleCell reports2026

ISG15 negatively regulates RIPK3-mediated cell death and viral pathogenesis.

Yi-Chieh Perng, Jessica M C Warsaw, Sachendra S Bais, Bradley E Hiller, Marissa C Locke, David J Morales-Heil, Chaoqun Li, Alissa R Young, Kristen J Monte, Robert E Schmidt and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

13 authors.

Yi-Chieh PerngDepartment of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Jessica M C WarsawDepartment of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Sachendra S BaisDepartment of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Bradley E HillerDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Marissa C LockeDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
David J Morales-HeilDepartment of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Chaoqun LiDepartment of Immunology, University of Pittsburgh School of Medicine, Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA 15213, USA.
Alissa R YoungDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Kristen J MonteDepartment of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Robert E SchmidtDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Douglas R GreenDepartment of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Yi-Nan GongDepartment of Immunology, University of Pittsburgh School of Medicine, Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA 15213, USA. Electronic address: ygong@houstonmethodist.org.
Deborah J LenschowDepartment of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: dlenschow@wustl.edu.

Funding

REGULATION OF INFLUENZA VIRUS INFECTION BY ISG15R01AI080672 · NIAID · WASHINGTON UNIVERSITY · PI LENSCHOW, DEBORAH J · 2009 to 2021
$2.9M
Mechanistic characterization of SARS-CoV2 associated kidney injuryR01DK130476 · NIDDK · WASHINGTON UNIVERSITY · PI LENSCHOW, DEBORAH J · 2021 to 2023
$1.2M
NIAID NIH HHS R01 AI080672NIDDK NIH HHS R01 DK130476
6 · The paper itself

Abstract

Necroptosis, a form of programmed, inflammatory necrosis, plays an important role in viral-host defense and inflammation. The receptor-interacting protein kinase 3 (RIPK3)/mixed lineage kinase domain-like pseudokinase (MLKL) pathway mediates necroptosis. Yet, the mechanisms that control necroptosis to limit immunopathology are poorly understood. Here, we report that interferon-stimulated gene 15 (ISG15) negatively regulates RIPK3-mediated cell death, including necroptosis, and limits immunopathology during chikungunya virus (CHIKV) infection. ISG15-deficient mice infected with CHIKV display increased levels of necroptosis, resulting in elevated proinflammatory cytokine and chemokine production, leading to increased lethality. This dysregulated host response is fully prevented when MLKL or RIPK3 is ablated in Isg15

Indexed as

Chikungunya virusCytokinesReceptor-Interacting Protein Serine-Threonine KinasesUbiquitinsAnimalsCell DeathHumansMiceMice, Inbred C57BLMice, KnockoutNecroptosisProtein KinasesTumor Necrosis Factor-alphaCytokinesG1p2 protein, mouseMLKL protein, mouseProtein KinasesReceptor-Interacting Protein Serine-Threonine KinasesRipk3 protein, mouseTumor Necrosis Factor-alphaUbiquitinschikungunya virusCHIKVCP: immunologyCP: microbiologyhomeostasisimmunopathologyISG15MLKLnecroptosisRIPK3

Identifiers

PMID42139056
PMCPMC13335134

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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 OpenQuestion graph.