Evidence map›Paper›PMID 41174694›Full record

ArticleJournal of neuroinflammation2025

SARS-CoV-2 spike triggers TLR7-dependent endolysosome dysfunction and senescence in human astrocytes.

Wendie A Hasler, Emily McKay, Gaurav Datta, Samantha Johnson, Neda Rezagholizadeh, Xuesong Chen

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neuroinflammation, 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

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

6 authors.

Wendie A HaslerDepartment of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, 504 Hamline Street, Room 112, Grand Forks, ND, 58203, USA.
Emily McKayDepartment of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, 504 Hamline Street, Room 112, Grand Forks, ND, 58203, USA.
Gaurav DattaDepartment of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, 504 Hamline Street, Room 112, Grand Forks, ND, 58203, USA.
Samantha JohnsonDepartment of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, 504 Hamline Street, Room 112, Grand Forks, ND, 58203, USA.
Neda RezagholizadehDepartment of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, 504 Hamline Street, Room 112, Grand Forks, ND, 58203, USA.
Xuesong ChenDepartment of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, 504 Hamline Street, Room 112, Grand Forks, ND, 58203, USA. xuesong.chen@und.edu.

Funding

Tat endolysosome escape and HANDR01MH119000 · NIMH · UNIVERSITY OF NORTH DAKOTA · PI CHEN, XUESONG, GEIGER, JONATHAN DAVID · 2019 to 2023
$2.6M
Intersection of HIV-1 Tat and SARS-CoV-2 S1 on neuroinflammationRF1MH134592 · NIMH · UNIVERSITY OF NORTH DAKOTA · PI CHEN, XUESONG · 2023 to 2023
$2.0M
17α-estradiol and sex-differences in HAND with methamphetamineR01DA059280 · NIDA · UNIVERSITY OF NORTH DAKOTA · PI Xuesong Chen · 2023 to 2026
$1.8M
NIDA NIH HHS DA059280NIDA NIH HHS R01 DA059280NIMH NIH HHS MH134592NIMH NIH HHS R01 MH119000NIMH NIH HHS RF1 MH134592
6 · The paper itself

Abstract

SARS-CoV-2 infection is associated with long-lasting neuropsychiatric and cognitive symptoms, collectively referred to as neuro-PASC. Emerging studies indicates that accelerate brain aging and cellular senescence in COVID brain could lead to altered neuroimmune responses and neurodegenerative outcomes. However, little is known about how cellular senescence is development in neuro-PASC. Here, we examined the role of spike protein subunit S1, a persistent viral antigen, in driving the development of cellular senescence in primary human astrocytes. We have demonstrated that S1 enters endolysosomes and induces endolysosome dysfunction and cellular senescence. Moreover, the multibasic motif is critical for such S1-induced damaging effects. Importantly, we identified Toll-like receptor 7 (TLR7), an endolysosome-resident pattern recognition receptor, as a critical mediator of S1-induced damaging effects. Mechanistically, S1 interacts with TLR7 at the site of the endolysosome lumen and activates p38 MAPK signaling of downstream of TLR7, which drive the development of cellular senescence. Together, these findings suggest that TLR7 mediates S1-induced endolysosome dysfunction and cellular senescence, and that TLR7 represents a therapeutic target for mitigating neuro-PASC.

Indexed as

AstrocytesCellular SenescenceLysosomesSARS-CoV-2Spike Glycoprotein, CoronavirusToll-Like Receptor 7Cells, CulturedCOVID-19HumansSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2TLR7 protein, humanToll-Like Receptor 7AstrocytesEndolysosomesNeuro-PASCSARS-CoV-2SenescenceSpike proteinTLR7

Identifiers

PMID41174694
PMCPMC12577261

What Socratic holds

Textmetadata
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 Socratic graph.