Role of The Virome in Parkinson's Disease

A number of viruses have been considered as potential causal factors or triggers in the pathogenesis of Parkinson’s disease (PD), ever since the occurrence of parkinsonism in patients affected by encephalitis lethargica 100 years ago. However, those previous studies each usually focused on single viral species, and although abundant data exist, it remains to this day inconclusive. We have developed a novel deep-sequencing based assay called ViroFind that allows us to detect every virus known to infect humans -the entire Virome- in clinical samples. Our preliminary studies, carried out in part using MJFF pilot funding support, showed that the human pegivirus (HPgV) from the flavivirus family is uniquely present in brains of PD patients. The key unanswered question is whether viruses may trigger, act as co-factors or even constitute biomarkers in PD. We will test the working hypothesis that HPgV and possibly other viruses may remain latent in the CNS of some individuals and reactivate intermittently. These events may lead over time to glial or neuronal damage, as well as a localized immune response and inflammation, which, in some people, may lead to the PD phenotype. In those circumstances, accumulation of alpha synuclein in PD may in fact be secondary, or even possibly a defense mechanism. We will test our hypothesis by using the approach of characterizing the entire Virome in affected areas of frozen post-mortem brain samples of patients with PD using ViroFind, and correlate those findings in the CSF and blood samples of those PD patients. We will then characterize the type of cells harboring those viruses in fixed contralateral brain tissue of the same PD patients. We will also mine existing OMICS database from PD patients for the presence of viruses. The rationale for those studies, firmly based on aforementioned publications and our preliminary data, is that successful completion of this project will provide a comprehensive, unbiased understanding of the role of HPgV and all the viral species in PD.