AUTHOR=Madani Sare , Amini Kumars , Habibi Seyed Amir Hassan , Shahhosseiny Mohammad Hassan , Mohammadian Taher TITLE=The relationship between herpesviruses and Parkinson’s disease: prevalence, viral load, and clinical implications JOURNAL=Acta Virologica VOLUME=Volume 70 - 2026 YEAR=2026 URL=https://www.frontierspartnerships.org/journals/acta-virologica/articles/10.3389/av.2026.14499 DOI=10.3389/av.2026.14499 ISSN=1336-2305 ABSTRACT=Parkinson’s disease (PD) is a complex neurodegenerative disorder characterized by dopaminergic neuronal loss, motor dysfunction, and a range of non-motor symptoms. While the etiology of PD remains elusive, emerging evidence suggests a significant role for latent herpesvirus infections in its pathogenesis. This study investigates the prevalence and viral loads of herpes simplex virus type 1 (HSV-1), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) in PD patients compared to age- and sex-matched healthy controls. Using multiplex PCR and quantitative PCR, we demonstrate a higher prevalence of HSV-1 and VZV in PD patients, with their viral loads correlating significantly with disease severity and elevated levels of interleukin-6 (IL-6), a marker of systemic inflammation. Our findings reveal that active herpesvirus infections exacerbate neuroinflammation, potentially accelerating dopaminergic neurodegeneration. While CMV and HSV-2 showed no significant differences, the co-infection of HSV-1 and VZV was associated with more severe non-motor symptoms, such as cognitive decline and depression. These results underscore the potential of targeting herpesvirus reactivation and associated inflammation as a novel therapeutic approach for managing PD. Antiviral therapies and vaccination strategies, particularly for HSV-1 and VZV, warrant further investigation to mitigate PD progression.