A virus long thought to be harmless might now play a key role in unraveling the mystery of Parkinson's disease. Human Pegivirus (HPgV), a virus that is normally found in blood and which was long believed to be harmless, has been found in patients diagnosed with Parkinson's disease in their brains. The research published on July 8 in JCI Insight has the potential to change scientists' understanding of the origin of the neurodegenerative disorder that strikes over 1 million Americans.Guided by Dr. Igor Koralnik, Northwestern Medicine chief of neuroinfectious diseases and global neurology in Chicago, the study detected HPgV in 50% of Parkinson's patients' autopsied brains—but none in the control group. "We were surprised to detect it in the brains of Parkinson's patients at such high frequency and not in controls," Koralnik said.HPgV, a member of the same virus family as hepatitis C, is usually symptomless and generally overlooked in clinical practice. Nevertheless, this new finding indicates that HPgV is possibly not as harmless as previously thought. The virus was found not only in the brains of infected patients but also in their spinal fluid—a sign that it has possibly infiltrated the central nervous system.Perhaps more fascinating is how individuals' immune systems respond to HPgV. These responses, says Koralnik, were highly variable and influenced by genetic considerations. Specifically, individuals carrying the Parkinson's-linked LRRK2 gene mutation exhibited unique immune responses, implying a possible interaction between the virus and the body's genetic topology.Parkinson's disease is mostly an idiopathic condition—i.e., most instances occur without a recognized genetic etiology. This has prompted researchers for many years to pursue environmental etiologies, such as toxin exposure and head injury. The potential viral link adds another twist to that theory. If HPgV is found to be causal, it would be one of the first known environmental factors directly implicated in Parkinson's disease development.This implies it might be an environmental factor that acts on the body differently than we previously understood," said Koralnik. "It might affect how Parkinson's arises, particularly in individuals with specific genetically derived backgrounds."Why HPgV Could Matter More Than We Thought?The researchers autopsied the brains of 10 Parkinson's patients and matched them with 14 brains of healthy individuals. HPgV was found in half of the Parkinson's brains but none of the healthy brains. Further, scientists detected evidence of more damage to the brain in the virus-positive patients, which further solidified the connection.They next examined blood samples from more than 1,000 people from the Parkinson's Progression Markers Initiative, a large, ongoing study supported in part by the Michael J. Fox Foundation. Just 1% of those with detectable HPgV in their blood, which suggests that the virus can evade detection or pass into the brain without being detected using routine blood tests.Parkinson's disease is marked by the death or damage of dopamine-producing neurons of the basal ganglia, which is a region of the brain that controls movement. When dopamine levels decline, symptoms such as trembling, stiffness, and poor coordination start to develop. But the disease also produces non-motor symptoms resulting from damage in other locations—such as fatigue, gastrointestinal problems, and blood pressure abnormalities.How Parkinson's Usually Progresses in the Brain?A characteristic of Parkinson's is the presence of Lewy bodies, aggregations of misfolded alpha-synuclein protein within brain cells. These deposits are thought to lead to cell death and loss of cognitive function.The new study opens up the possibility that HPgV either directly injures neurons or provokes immune reactions that make alpha-synuclein aggregation worse. Both possibilities offer new leads for investigation, diagnosis, and ultimately treatment.As Parkinson's advances, most patients develop cognitive symptoms ranging from mild forgetfulness and difficulty concentrating to frank Parkinson's dementia. This dementia is closely associated with Lewy body accumulation and progresses over time.Stress, depression, and some drugs make cognitive symptoms more severe, so early detection and management are important. If HPgV is found to be affecting these changes in cognition, it would reveal the possibility of preventive interventions targeting viral suppression or immune modulation.This research is just the start. Koralnik and his colleagues are now working on two main questions: how frequently does HPgV invade the brain, and how does its invasion relate to the severity of the disease? They're also exploring whether there are other viruses with such effects, particularly in people with genetic mutations such as LRRK2."We also want to know how genes and viruses communicate with each other; information that may uncover why Parkinson's starts and may inform the next generation of therapies," Koralnik said.Future research might investigate whether antiviral treatments or vaccines could slow the development of Parkinson's in virus-positive individuals. Another option is the use of HPgV as an earlier disease biomarker or disease tracking.This study highlights an overarching trend in medicine today: the reevaluation of microbes previously known to be innocuous. From the bacteria in our guts to the latent viruses in our systems, we are finding that these innocuous-looking commuters on our body highways have significant long-term impacts on health.For families and patients with Parkinson's disease, this study provides a glimmer of hope—if not for a quick fix, then for better understanding and more individualized means of care.As with so many scientific advances, the discoveries raise as many questions as they resolve but for a disease as multifaceted and life-changing as Parkinson's, even a step in the direction of shedding light on its causes is a leap of giant proportions toward future treatments.