Less-known virus found in half of Parkinson’s brain

Scientists have discovered that human spinal cord virus (a virus that is relatively fuzzy in the same family as hepatitis C) is found in the brains of 50% of Parkinson’s patients, and not in healthy control brains.

Unexpected findings suggest that the persistent virus may play a previously unknown role in neurodegenerative diseases affecting more than 10 million people worldwide.

The researchers used an advanced virus detection system called ViRofind to scan brain tissue in 10 Parkinson’s patients and 14 age-matched controls. The technique can identify each virus known to infect humans, suggesting that human grape disease (HPGV) appears only in the brain of Parkinson’s disease, which is statistically significant differentially raises questions about virus triggers in neurodegeneration.

Genetic mutant shape virus response

This study reveals differences in patients’ response to sampivirus infection based on their genetic composition. Those who carry mutations in the LRRK2 gene, a known Parkinson’s risk factor, responded completely oppositely to the virus compared to patients without mutations.

When virus levels rise, patients with normal genetics will show enhanced immune signaling, while patients with LRRK2 mutations will inhibit immune responses. This genetic dependency pattern affects a network of 157 genes centered on YWHAB, which helps regulate cellular function and is essential for brain health.

The team analyzed brain tissue in three regions: the amygdala, posterior shell, and superior frontal cortex. They confirmed the presence of the virus using genetic sequencing and antibody staining that revealed the flaretin virus protein in brain cells called oligodendrocytes.

Immune system disruption

Patients with grape virus in the brain exhibited more advanced disease pathology, including higher levels of Tau protein tangles (a marker of neurodegeneration). They also have elevated levels of complexin-2, a protein involved in neurotransmitter release, suggesting that brain communication has changed.

Blood analysis shows other immune destruction in spinoprotein virus-positive patients:

• Higher IGF-1 levels: Implications of metabolic changes
• Ps65-ubiquitin: Indicates interrupted cellular cleaning process
• Change IL-4 signaling: Influence anti-inflammatory response
• The persistent virus exists: Detected in longitudinal studies over the years

Virus persistence and replication

Human grape disease belongs to the Flavivivirus family, including hepatitis C and West Nile virus. Unlike many viruses with dormant infections, Pegivivirus appears to replicate actively in brain tissue. The virus usually causes no symptoms and may last for years or decades in 1-5% of the population.

In these patients, while the virus is absent in blood samples, the presence of the virus suggests that specific factors may contribute to its entry into the nervous system. Blood-brain barrier dysfunction or neuroinflammatory changes associated with Parkinson’s disease may create diseases that allow virus invasion.

Longitudinal analysis of blood samples from Parkinson’s Progress Marking Initiative suggests that viral infections may last for more than two years, with some patients eventually clearing the virus while others maintain persistent infection regardless of the disease status.

Impact on treatment

This finding adds to growing evidence that viral infection may be an environmental trigger for Parkinson’s disease. Historical examples include the 1918 encephalitis encephalitis epidemic, after which some survivors developed Parkinson’s symptoms a few years later.

Recently, West Nile virus, St. Louis encephalitis virus and Japanese encephalitis virus infection have been associated with Parkinson’s disease. Current findings suggest that even seemingly harmless persistent viruses can lead to neurodegeneracy under certain conditions.

The research team stressed that their work demonstrated association rather than causality. However, consistent patterns across brain regions and genetically dependent immune responses support the hypothesis that viral infection interacts with host genetics to influence disease progression.

Future studies will need to determine whether pegivirus infection occurs before or after symptoms of Parkinson’s disease begin, and whether targeting viral infection or associated immune pathways can provide therapeutic benefits. These findings highlight the complex interactions between genetics, immunity and environmental factors in neurodegenerative diseases.

Related