Summary: New research indicates that a virus previously considered harmless may be associated with Parkinson’s disease. Scientists detected Human Pegivirus (HPgV) in the brains and cerebrospinal fluid of several people with Parkinson’s but not in control samples, challenging the assumption that this virus is always benign.
The study found that individuals with HPgV showed distinct immune and molecular profiles and more advanced neuropathological changes. Those differences were further shaped by genetic factors such as LRRK2 mutations. Together, these results point to a possible environmental contributor to Parkinson’s and prompt further investigation into how viral infections and genetics interact in disease development.
Key Facts
- HPgV Detection: Identified in 50% of Parkinson’s post-mortem brains studied (5 of 10) and not detected in the 14 control brains.
- Immune Impact: Virus presence correlated with altered immune signaling in both brain and blood samples; some immune responses varied by genotype.
- Gene–Virus Interaction: The immune response to HPgV differed in people with the LRRK2 Parkinson’s-related mutation, suggesting gene–virus interactions could influence disease processes.
Source: Northwestern University
Overview
Researchers at Northwestern Medicine report that Human Pegivirus (HPgV), a blood-borne virus previously thought to be harmless, was found in multiple brain and spinal fluid samples from people with Parkinson’s disease and absent from age- and sex-matched control samples. The results, published in JCI Insight, suggest HPgV may shape immune responses and neuropathology in a subset of Parkinson’s patients.
Igor Koralnik, MD, chief of neuroinfectious diseases and global neurology at Northwestern Medicine, and colleagues used an unbiased viral sequencing tool called ViroFind to search for human-infecting viruses in post-mortem brain tissue. Their aim was to explore environmental triggers—specifically viral agents—that might contribute to Parkinson’s disease alongside genetic risk factors.
The investigators detected HPgV in half of the Parkinson’s brains examined (5 of 10) and confirmed its presence by additional methods in some cases, while all 14 control brains were negative. HPgV was also present in the cerebrospinal fluid of affected individuals but not in the controls. Although HPgV belongs to the same viral family as hepatitis C, it has not previously been linked to disease in humans.
Patients whose brains contained HPgV showed more advanced neuropathological changes, including higher Braak staging and increases in proteins such as Complexin-2, along with altered levels of other brain proteins. In blood samples, those with HPgV exhibited biochemical markers consistent with disrupted metabolism or mitophagy, including higher IGF-1 and lower phosphorylated ubiquitin (pS65-ubiquitin).
Analysis of RNA sequencing data revealed changes in immune signaling associated with HPgV infection. One consistent finding was suppression of IL-4 signaling in both brain and blood samples from HPgV-positive patients. Longitudinal blood studies using samples from more than 1,000 participants in the Parkinson’s Progression Markers Initiative showed that HPgV viral load and immune signaling varied over time and that the pattern depended on genotype.
Notably, people carrying a Parkinson’s-associated LRRK2 gene mutation exhibited a different immune response to HPgV compared with Parkinson’s patients without the mutation. The research identified YWHAB as a central hub gene in the LRRK2-dependent response and described altered relationships among immune-related genes such as NFKB1, ITPR2, and LRRK2 itself in HPgV-positive patients.
Dr. Koralnik emphasized that these results do not prove causation but raise important questions about how common HPgV infection of the brain may be and whether viral infections can interact with genetic risk factors to influence Parkinson’s onset or progression. The team plans larger studies to determine the prevalence of HPgV in Parkinson’s populations and to dissect whether the virus has a unique effect compared with other viral infections.
The blood sample analyses used resources from the Parkinson’s Progression Markers Initiative, established to build a large biosample library for accelerating discovery and therapeutic development. According to the Parkinson’s Foundation, more than one million people in the United States are living with Parkinson’s disease, with approximately 90,000 new diagnoses each year; that total is projected to rise in the coming decade.
About this Parkinson’s disease research news
Author: Mark Rudi
Source: Northwestern University
Contact: Mark Rudi – Northwestern University
Image: Image credit: Neuroscience News
Original Research: Open access. “Human pegivirus alters brain and blood immune and transcriptomic profiles of patients with Parkinson’s disease” by Igor Koralnik et al., JCI Insight. DOI: 10.1172/jci.insight.189988
Abstract
Human pegivirus alters brain and blood immune and transcriptomic profiles of patients with Parkinson’s disease
Parkinson’s disease is a neurodegenerative disorder influenced by both genetic and environmental factors. Viral infections are plausible environmental triggers that may modify Parkinson’s pathology. Using ViroFind for comprehensive virome sequencing together with quantitative PCR, the study identified Human Pegivirus (HPgV) in 5 of 10 (50%) Parkinson’s disease brains examined, with immunohistochemical confirmation in selected cases. All 14 age- and sex-matched control brains were negative for HPgV.
HPgV-positive Parkinson’s patients showed increased neuropathology measured by Braak stage and elevated Complexin-2, while blood-positive individuals displayed metabolic or mitophagy-related changes such as higher IGF-1 and lower pS65-ubiquitin. RNA sequencing highlighted altered immune signaling in HPgV-infected samples, notably suppression of IL-4 pathways in both brain and blood. Longitudinal blood analysis revealed a genotype-dependent viral response: HPgV titer correlated with IL-4 signaling in a manner dependent on LRRK2 genotype.
YWHAB emerged as a key hub in the LRRK2-associated response, showing modified relationships with immune-related genes including NFKB1 and ITPR2. Overall, these findings suggest HPgV may influence Parkinson’s pathology and underscore a complex interplay between viral infection, immune responses, and neuropathogenesis.