Evidence map›Paper›PMID 41959182›Full record

ArticlebioRxiv : the preprint server for biology2026

ISG15-USP18 signaling restrains viperin-dependent metabolic antiviral restriction.

Niklas L Kahler, Sefanit Rezene, Florine Em Scholte, Anoop T Ambikan, Elisa Saccon, Vanessa M Monteil, Prajakta Naval, Robin Macmillan, Simon Frick, Jenny Norén and 12 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 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

22 authors.

Niklas L KahlerSystems Virology Laboratory, Division of Clinical Microbiology, Department of Laboratory Medicine, Campus Flemingsberg, Karolinska Institutet, Sweden.
Sefanit RezeneSystems Virology Laboratory, Division of Clinical Microbiology, Department of Laboratory Medicine, Campus Flemingsberg, Karolinska Institutet, Sweden.
Florine Em ScholteViral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Anoop T AmbikanSystems Virology Laboratory, Division of Clinical Microbiology, Department of Laboratory Medicine, Campus Flemingsberg, Karolinska Institutet, Sweden.
Elisa SacconDepartment of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
Vanessa M MonteilDivision of Clinical Microbiology, Department of Laboratory Medicine, Campus Flemingsberg, Karolinska Institutet, Sweden.
Prajakta NavalDepartment of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Robin MacmillanSystems Virology Laboratory, Division of Clinical Microbiology, Department of Laboratory Medicine, Campus Flemingsberg, Karolinska Institutet, Sweden.
Simon FrickSystems Virology Laboratory, Division of Clinical Microbiology, Department of Laboratory Medicine, Campus Flemingsberg, Karolinska Institutet, Sweden.
Jenny NorénSystems Virology Laboratory, Division of Clinical Microbiology, Department of Laboratory Medicine, Campus Flemingsberg, Karolinska Institutet, Sweden.
Magda LourdaSystems Virology Laboratory, Division of Clinical Microbiology, Department of Laboratory Medicine, Campus Flemingsberg, Karolinska Institutet, Sweden.
Ali MirazimiSystems Virology Laboratory, Division of Clinical Microbiology, Department of Laboratory Medicine, Campus Flemingsberg, Karolinska Institutet, Sweden.
Yenan T BrycesonDepartment of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
Ronaldo Lira-JuniorDivision of Oral Diagnostics and Surgery, Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden.
Vibhu PrasadDepartment of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Ákos VégváriDepartment of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-1287-0906
Ujjwal NeogiSystems Virology Laboratory, Division of Clinical Microbiology, Department of Laboratory Medicine, Campus Flemingsberg, Karolinska Institutet, Sweden.ORCID 0000-0002-0844-3338
Connor Gg BamfordSchool of Biological Sciences and Institute for Global Food Security (IGFS), Queen's University Belfast; Belfast, Belfast, Ireland.
Anders HoferDepartment of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.ORCID 0000-0003-2890-2957
Eric BergeronViral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Janne PurhonenDivision of Clinical Microbiology, Department of Laboratory Medicine, Campus Flemingsberg, Karolinska Institutet, Sweden.
Soham GuptaSystems Virology Laboratory, Division of Clinical Microbiology, Department of Laboratory Medicine, Campus Flemingsberg, Karolinska Institutet, Sweden.ORCID 0000-0003-1136-3010

Funding

Origin of the innate immunity suppression caused by nairovirus' protease activityR01AI151006 · NIAID · UNIVERSITY OF GEORGIA · PI PEGAN, SCOTT DUSAN · 2020 to 2024
$2.1M
NIAID NIH HHS R01 AI151006
6 · The paper itself

Abstract

Type I interferon (IFN-I) responses are tightly regulated to balance antiviral defense with cellular homeostasis. In humans, interferon-stimulated gene 15 (ISG15) functions as a critical negative regulator of IFN-I signaling by stabilizing the IFN negative regulator USP18, yet the functional consequences of ISG15 deficiency remain elusive. Here, we show that the loss of ISG15 exaggerates the JAK-STAT activation and, downstream, amplifies multiple ISGs including the nucleotide-modifying enzyme RSAD2 (viperin). Our quantitative proteomics, genetic reconstitution, and signaling analyses establish that defective USP18 stabilization skews the IFN response towards viperin expression. This amplified ISG network promotes viperin-catalyzed accumulation of the antiviral nucleotide analog ddhCTP, resulting in enhanced inhibition of viral RNA synthesis and the replication of Crimean-Congo hemorrhagic fever virus and SARS-CoV-2. Together, these findings demonstrate an ISG15-USP18-viperin axis that can be targeted to boost the metabolic antiviral restriction.

Identifiers

PMID41959182
PMCPMC13060826

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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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 OpenQuestion graph.