New research from Northwestern Medicine detects a common, but usually harmless virus in the brains of Parkinson’s patients
New research from Northwestern Medicine published in JCI Insight has found that a usually harmless virus might be an environmental trigger or contributor to Parkinson’s disease, which affects more than one million people in the United States. While some cases are linked to genetics, most Parkinson’s cases are not, and the cause is unknown.
“We wanted to investigate potential environmental factors – such as viruses – that might contribute to Parkinson’s disease,” said Igor Koralnik, MD, chief of Neuroinfectious Diseases and Global Neurology in the Department of Neurology. “Using a tool called ‘ViroFind’, we analyzed post-mortem brain samples from individuals with Parkinson’s and from those who died of other causes. We searched for all known human-infecting viruses to identify any differences between the two groups.”
Northwestern Medicine scientists detected the Human Pegivirus (HPgV) in the brains of individuals with Parkinson’s disease, but not in those without it. While HPgV belongs to the same family as hepatitis C and is a blood-borne virus, it is not known to cause any disease.
“HPgV is a common, symptomless infection previously not known to frequently infect the brain,” Koralnik said. “We were surprised to find it in the brains of Parkinson’s patients at such high frequency and not in the controls. Even more unexpected was how the immune system responded differently, depending on a person’s genetics. This suggests it could be an environmental factor that interacts with the body in ways we didn’t realize before. For a virus that was thought to be harmless, these findings suggest it may have important effects, in the context of Parkinson’s disease. It may influence how Parkinson’s develops, especially in people with certain genetic backgrounds.”
Koralnik and his team, including postdoctoral fellow Barbara Hanson, PhD, studied post-mortem brains from 10 people with Parkinson’s and 14 without. They found HPgV in the post-mortem brains of five out of 10 people with Parkinson’s and none of the 14 control brains. It was also present in the spinal fluid of Parkinson’s patients, but not in the control group. Individuals with HPgV in their brains exhibited more advanced or distinct neuropathological changes, including increased tau pathology and altered levels of certain brain proteins.
For the blood analysis, the investigators used samples from over 1,000 participants in the Parkinson’s Progression Markers Initiative, which was launched by The Michael J. Fox Foundation and scientists to create a robust biosample library to help speed scientific breakthroughs and new treatments.
“With the blood samples, we observed similar immune-related changes, mirroring those found in the brain,” Koralnik said. “People who had the virus showed different signals from the immune system than those who didn’t, and this pattern was the same, no matter the genetics. But as we followed each person over time, we saw a more complicated picture.”
The study found that in patients with a certain Parkinson’s-related gene mutation – LRRK2 – the signals from the immune system were different in response to the virus compared to Parkinson’s patients without the mutation.
“We plan to look more closely at how genes like LRRK2 affect the body’s response to other viral infections to figure out if this is a special effect of HPgV or a broader response to viruses,” Koralnik added.
Going forward, the research team plans to study more people to find out how common the HPgV virus is in Parkinson’s patients and whether it plays a role in the disease.
“One big question we still need to answer is how often the virus gets into the brains of people with or without Parkinson’s,” said Koralnik. “We also aim to understand how viruses and genes interact; insights that could reveal how Parkinson’s begins and could help guide future therapies.”
According to the Parkinson’s Foundation, over one million people in the United States are living with Parkinson’s disease and 90,000 new cases are diagnosed every year. The number of people living with Parkinson’s disease is expected to rise to 1.2 million by 2030.
This study was supported in part by the Michael J. Fox Foundation research grant MJFF-021128 and by NIH National Institute on Aging grant P30AG072977.
For more information on Parkinson’s disease, visit nm.org.