Evidence map›Paper›PMID 40450318›Full record

ArticleJournal of neuroinflammation2025

Temporally resolved single-cell RNA sequencing reveals protective and pathological responses during herpes simplex virus CNS infection.

Xiangning Ding, Xin Lai, Ida H Klaestrup, Sara R N Jensen, Morten M Nielsen, Kasper Thorsen, Marina Romero-Ramos, Yonglun Luo, Lin Lin, Line S Reinert and 1 more

Abstract read
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. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
–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

11 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Single-cell RNA sequencing offers novel perspectives in viral infection research.Frontiers in cellular and infection microbiology · 2026
    Pooled it
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  11. Advances in Single-Cell Sequencing for Infectious Diseases: Progress and Perspectives.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    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

11 authors.

Xiangning DingDepartment of Biomedicine, Aarhus University, Aarhus, Denmark.
Xin LaiDepartment of Biomedicine, Aarhus University, Aarhus, Denmark.
Ida H KlaestrupDepartment of Biomedicine, Aarhus University, Aarhus, Denmark.
Sara R N JensenDepartment of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
Morten M NielsenDepartment of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
Kasper ThorsenDepartment of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
Marina Romero-RamosDepartment of Biomedicine, Aarhus University, Aarhus, Denmark.
Yonglun LuoDepartment of Biomedicine, Aarhus University, Aarhus, Denmark.
Lin LinDepartment of Biomedicine, Aarhus University, Aarhus, Denmark.
Line S Reinert *Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Søren R Paludan *Department of Biomedicine, Aarhus University, Aarhus, Denmark. srp@biomed.au.dk.

Funding

Danish Agency for Science and Higher Education 5229-00009BDanmarks Grundforskningsfond DNRF164European Research Council 786602Lundbeck Foundation R359-2020-2287The novo nordisk foundation NNF23OC0084931
6 · The paper itself

Abstract

backgroundHerpes Simplex Virus 1 (HSV-1) is a neurotropic virus causing encephalitis and post-infectious complications. Infections can induce a range of acute, subacute, and progressing brain disease, and in recent years it has emerged that immune responses are involved in the pathogenesis of these diseases.

methodsMice were infected with HSV-1 through corneal infection, and the brain stem was analyzed using single-cell and GeoMx spatial transcriptomics. Through these technologies we profiled temporal transcriptomic changes in cell populations, pathways, and cell-cell communication associated with antiviral activity and inflammation-induced disturbance of physiological brain structures and activities.

resultsWe found that microglia proportions increased early after HSV-1 infection, followed by monocyte influx and later by T cells. The blood-brain barrier was disrupted, and transcriptomic profiles associated with homeostatic brain transcriptional activities were altered. Early transcriptional responses were dominated by antiviral and inflammatory activities. A microglia subpopulation with high type I interferon and chemokine expression localized to infection sites, likely mediating antiviral defense and immune recruitment. Monocyte subpopulations displayed a broader activation profile than microglia and was a central mediator of crosstalk between immune cells. Cytokines from microglia, monocytes, and T cells reprogrammed brain cells, notably endothelial cells and oligodendrocytes, disrupting brain functions. Comparing datasets from various brain diseases revealed the identified microglia subpopulation as specific to viral infections.

conclusionsThis study identifies a unique population of virus-activated microglia with antiviral and proinflammatory properties and reveals monocytes to be a key driver of interactions driving pathology in the virus-infected brain.

Indexed as

Encephalitis, Herpes SimplexHerpes SimplexHerpesvirus 1, HumanSequence Analysis, RNASingle-Cell AnalysisAnimalsBrainFemaleMiceMice, Inbred C57BLMicrogliaTranscriptomeInfection-induced brain inflammationSingle-cell RNA sequencingViral brain infection

Identifiers

PMID40450318
PMCPMC12125739

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.