Evidence map›Paper›PMID 40909558›Full record

ArticlebioRxiv : the preprint server for biology2025

SARS-CoV-2 nucleocapsid induces hyperinflammation and vascular leakage through the Toll-like receptor signaling axis in macrophages.

Zhenlan Yao, Pablo A Alvarez, Carolina Chavez, Yennifer Delgado, Prashant Kaushal, David Austin, Qian Li, Yanying Yu, Anne K Zaiss, Vaithilingaraja Arumugaswami and 6 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. 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

5 · Who and what money

Authors and funding

16 authors.

Zhenlan YaoDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.ORCID 0000-0001-6588-0633
Pablo A AlvarezDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.
Carolina ChavezDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.
Yennifer DelgadoDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.
Prashant KaushalDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.
David AustinDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Qian LiDepartment of Medicine, University of California, Los Angeles, CA 90095, USA.
Yanying YuCenter for Infection Biology, School of Basic Medical Sciences, Tsinghua University, Beijing, China.
Anne K ZaissDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Vaithilingaraja ArumugaswamiDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Qiang DingCenter for Infection Biology, School of Basic Medical Sciences, Tsinghua University, Beijing, China.
Jeffrey J HsuDepartment of Medicine, University of California, Los Angeles, CA 90095, USA.
Robert DamoiseauxDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Mehdi BouhaddouDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.
Alexander HoffmannDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.ORCID 0000-0002-5607-3845
Melody M H LiDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.

Funding

Unraveling alphavirus neuroinvasion: Molecular insights from a stem cell based blood-brain barrier modelF31AI179235 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ALVAREZ, PABLO · 2024 to 2025
$68k
NIAID NIH HHS F31 AI179235
6 · The paper itself

Abstract

Tens of thousands of severe COVID-19 cases are hospitalized weekly in the U.S., often driven by an imbalance between antiviral responses and inflammatory signaling, leading to uncontrolled cytokine secretion. The SARS-CoV-2 nucleocapsid (N) protein is a known immune antagonist, but its role in macrophage-driven cytokine storms is unclear. We demonstrate that N functions in a pathway-specific manner, specifically amplifying nuclear factor κB-related transcripts upon Toll-like receptor 7/8 stimulation. Moreover, we show that this is a conserved feature of pathogenic coronaviruses, with the delta variant N being the most pro-inflammatory. Our interaction networks suggest the delta variant N drives inflammation through interactions with several stress granule-related proteins. Profiling of secreted cytokines revealed that supernatants from the delta variant N-expressing macrophages disrupt brain and heart endothelial barriers, implicating N in COVID-19-associated cognitive and cardiac complications. Our findings highlight N-mediated immune imbalance as a driver of severe COVID-19 and identify N as a promising therapeutic target to mitigate hyperinflammation.

Identifiers

PMID40909558
PMCPMC12407974

What OpenQuestion holds

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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.