Evidence map›Paper›PMID 40626361›Full record

ArticleJCI insight2025

Human pegivirus alters brain and blood immune and transcriptomic profiles of patients with Parkinson's disease.

Barbara A Hanson, Xin Dang, Pouya Jamshidi, Alicia Steffens, Kaleigh Copenhaver, Zachary S Orban, Bernabe Bustos, Steven J Lubbe, Rudolph J Castellani, Igor J Koralnik

Abstract read
In one paragraph

Article in JCI insight, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Interpreting Viral Associations in Neurodegenerative Diseases.International journal of molecular sciences · 2026
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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

10 authors.

Barbara A HansonDavee Department of Neurology.
Xin DangDavee Department of Neurology.
Pouya JamshidiDepartment of Pathology.
Alicia SteffensDepartment of Neurological Surgery, and.
Kaleigh CopenhaverDavee Department of Neurology.
Zachary S OrbanDavee Department of Neurology.
Bernabe BustosDavee Department of Neurology.
Steven J LubbeDavee Department of Neurology.
Rudolph J CastellaniDepartment of Pathology.
Igor J KoralnikDavee Department of Neurology.

Funding

Research Education Core FP30AG072977 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI ROBERT J VASSAR · 2021 to 2026
$26.3M
NIA NIH HHS P30 AG072977
6 · The paper itself

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder with both genetic and environmental factors contributing to pathogenesis. Viral infections are potential environmental triggers that influence PD pathology. Using ViroFind, an unbiased platform for whole virome sequencing, along with quantitative PCR (qPCR), we identified human pegivirus (HPgV) in 5 of 10 (50%) of PD brains, confirmed by IHC in 2 of 2 cases, suggesting an association with PD. All 14 age- and sex-matched controls were HPgV negative. HPgV-brain positive patients with PD showed increased neuropathology by Braak stage and Complexin-2 levels, while those positive in the blood had higher IGF-1 and lower pS65-ubiquitin, supporting disruption in metabolism or mitophagy in response to HPgV. RNA-Seq revealed altered immune signaling in HPgV-infected PD samples, including consistent suppression of IL-4 signaling in both the brain and blood. Longitudinal analysis of blood samples showed a genotype-dependent viral response, with HPgV titers correlating directly with IL-4 signaling in a LRRK2 genotype-dependent manner. YWHAB was a key hub gene in the LRRK2 genotypic response, which exhibited an altered relationship with immune-related factors, including NFKB1, ITPR2, and LRRK2 itself, in patients with PD who are positive for HPgV. These results suggest a role for HPgV in shaping PD pathology and highlight the complex interplay between viral infection, immunity, and neuropathogenesis.

Indexed as

BrainParkinson DiseaseTranscriptomeAgedFemaleHumansMaleMiddle AgedGenetic variationNeurodegenerationNeuroscienceParkinson diseaseVirology

Identifiers

PMID40626361
PMCPMC12244338

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.