Summary: New research suggests that a previously harmless virus may be linked to Parkinson’s disease. Scientists were able to detect human PEGivirus (HPgV) in the brains and cerebrospinal fluid of Parkinson’s patients, but not in control groups. This refutes the assumption that the virus is harmless.
The results show that patients with the virus exhibited specific immune responses and advanced brain changes, which were further influenced by genetic mutations such as LRRK2. This discovery points to a possible environmental factor in the development of Parkinson’s disease and opens new avenues for research into viral and genetic interactions.
Key data
- HPV detection: It is present in 50% of the brains of Parkinson’s patients, but not in the control group.
- Immune interactions: The presence of the virus alters signals from the immune system, which are genetically determined.
- Possible triggers: This suggests that viruses can interact with genes and thus contribute to the development of Parkinson’s disease.
Source: Northwestern University
New research from Northwestern Medicine suggests that a normally harmless virus may be an environmental trigger or contributor to Parkinson’s disease, which affects more than 1 million people in the United States.
In some cases there is a genetic predisposition, but in most cases of Parkinson’s disease this is not the case and the cause is unknown.
The new findings are published in the latest issue of JCI Insight.
“We wanted to explore the role that environmental factors might play in the development of Parkinson’s disease,” explained Dr. Igor Koralnik, chief of Neuroinfectious Diseases and Global Neurology at Northwestern Medicine. Understanding these external contributors is crucial, as they could offer new insights into the disease’s origins and potential preventive strategies. While genetics have been studied extensively, the impact of environmental triggers remains less clear, prompting the team to investigate this area thoroughly.
Among the various environmental factors considered, viruses stood out as a significant focus of the study. The researchers hypothesized that viral infections could potentially influence neurological health and contribute to the onset or progression of Parkinson’s disease. By examining this connection, the team aims to shed light on how common pathogens might affect brain function and open new avenues for early diagnosis and treatment of this debilitating disorder.
Using the ViroFind tool, we analyzed postmortem brain samples from Parkinson’s patients and patients who died from other causes. We searched for all known viruses that infect humans to identify differences between the two groups.
Researchers at Northwestern Medicine have discovered the hepatitis C virus (HPV) in the brains of Parkinson’s patients, but not in people without Parkinson’s disease. Although HPV belongs to the same family as hepatitis C virus and is transmitted through blood, it is not known whether it causes the disease.
“HPV is a common, asymptomatic infection that was not previously known to frequently affect the brain,” said Dr. Koralnik.
We were surprised that this occurred so frequently in the brains of Parkinson’s patients compared to control groups. Even more surprising was that the immune system responded differently, depending on each individual’s genetic predisposition.
“This suggests that it may be an environmental factor that interacts with the body in a way that we didn’t know about before.”
Although the virus was once thought to be harmless, these findings suggest that it may have important effects on Parkinson’s disease. It may influence the development of the disease, especially in people with certain genetic predispositions.
Dr. Koralnik and his team, including postdoctoral researcher Dr. Barbara Hansen, examined the brains of ten Parkinson’s patients and 14 healthy individuals. They found HPgV in the brains of five of the ten Parkinson’s patients and none of the 14 control subjects.
This was also seen in the cerebrospinal fluid of Parkinson’s patients, but not in the control group. Individuals with HPgV in the brain showed more advanced or pronounced neuropathological changes, including increased tau pathology and altered levels of certain brain proteins.
For the blood test, the researchers used samples from more than 1,000 participants in the Parkinson’s Progression Markers Initiative, a project led by the Michael J. Fox Foundation and scientists. It created a vast library of biological samples to accelerate scientific advances and new treatments.
Dr. Koralnik said that in blood samples, we saw similar changes in the immune system as in the brain.
People infected with the virus showed different immune system signals than people without the infection. This pattern was consistent, regardless of genetic predisposition. However, if we observe each individual over a long period of time, a more complex picture emerges.
The study found that in patients with a specific genetic mutation linked to Parkinson’s disease (LRRK2), the immune system’s signals in response to the virus were different than in patients without Parkinson’s disease.
“We plan to further investigate how genes like LRRK2 affect the body’s response to other viral infections to determine whether this is a specific effect of HPgV or a more general response to the virus,” Dr. Koralnik added.
In the future, the research team wants to test more people to find out how often HPgV occurs in patients with Parkinson’s disease and whether it plays a role in the disease.
“A big question we still have to answer is how often the virus enters the brains of people with or without Parkinson’s disease,” Dr. Koralnik said.
We are also trying to understand how viruses and genes interact. These findings could shed light on the development of Parkinson’s disease and serve as the basis for future treatments.
According to the Parkinson’s Foundation, more than one million people in the United States have Parkinson’s disease. An estimated 90,000 new cases are diagnosed each year. The number of people with Parkinson’s is expected to increase to 1.2 million by 2030.
Abstract
Human pegivirus alters immune and transcriptome profiles in the brain and blood of patients with Parkinson’s disease.
Parkinson’s disease (PD) is a neurodegenerative disorder whose pathogenesis is influenced by genetic and environmental factors. Viral infections are potential environmental factors that influence the pathology of Parkinson’s disease.
Using VeroFind, an independent whole virome sequencing platform, and quantitative PCR (qPCR), we detected human pegyvirus (HPgV) in 5 of 10 (50%) PD brains. In 2 of 2, IHC confirmed this, suggesting a link to PD. All 14 age- and sex-matched controls were HPgV-negative.
In PD patients with positive HPgV results in the brain, increased neuropathology was observed based on break stage and complexin-2 levels, while positive blood tests showed increased IGF-1 and reduced pS65 ubiquitin levels. This suggests altered metabolism or mitophagy in response to HPgV.
RNA-Seq revealed immune signaling in HPgV-infected PD samples, including consistent suppression of IL-4 signaling in both brain and blood.
Longitudinal analysis of blood samples revealed a genotype-dependent viral response, with HPgV titers directly correlated with IL-4 signaling in a LRRK2 genotype-dependent manner.
JHWHABGenotypic LRRK2 was a key gene in the response, showing altered association with immune factors including NFKB1, ITPR2, and LRRK2 itself in HPgV-positive PD patients.
These results suggest that HPgV plays a role in the pathogenesis of PD pathology and highlight the complex interplay between viral infection, immunity, and neuropathogenesis.
