HSV-1 Infection and Parkinson's Disease Risk: Mechanisms and Implications
HSV-1 Infection and Parkinson's Disease Risk: Mechanisms and Implications
Mina Soleimani,1,*Alireza Faeghi,2
1. Department of Laboratory Science, Faculty of Paramedicine, Mashhad Medical Science, Islamic Azad University, Mashhad, Iran 2. Department of Laboratory Sciences, Faculty of Paramedicine, Aligudarz Branch, Islamic Azad University, Aligudarz, Iran
Introduction: Parkinson's disease (PD) is a neurological disorder and the second most common neurodegenerative disease in the over-65 population, whose prevalence will nearly double by 2030; it is characterized by symptoms such as resting tremors, muscle rigidity, bradykinesia, and postural instability.
Additionally to host genetics and environmental factors, pathogens can play a role in Parkinson's disease (PD). Herpes simplex virus type 1 (HSV-1) is a DNA virus that can induce herpes and is a member of the herpesviridae family of pathogens.
HSV-1 is widespread in the brain of persons in the latent form and can infect the central nervous system (CNS), which is connected with the severity of Parkinson's disease; As a side effect of HSV-1 viral encephalitis, signs of parkinsonism appear. Disruption of the body's immune system may play a part in Parkinson's disease autoimmunity by reactivity with the human amyloid protein alpha-synuclein (α-synuclein).
Methods: A systematic search was conducted from 2010 to 2023 in scientific databases such as PubMed, Scopus, Google Scholar, and the World Health Organization (WHO) website. The purpose of the research was to investigate the molecular biology, immunology, and genetics of HSV-1 infection in patients with Parkinson's disease and healthy controls. The search terms included "Parkinson's disease," and "HSV-1".
Results: The protein α-synuclein, which is compacted in the presynaptic terminals of dopaminergic neurons in the pars substantia nigra and has a crucial role in the start and progression of neurodegeneration in Parkinson's disease. Furthermore, the existence of molecular mimicry regions in α-synuclein that stimulate immunological cross-reaction with the HSV-1 peptide (UI42) can cause nerve injury, and the response with antibodies generated against HSV-1 in past infections can accelerate the progression of PD disease.
On the other hand, HSV-1 infection can cause the accumulation and deposition of -synuclein in the brain by altering the microbiota composition of the intestinal nervous system and the production of curli protein from its producing bacteria, thereby accelerating the neurodegenerative process in PD patients.
HSV-1 can alter the host's innate immunity, particularly the immune response mediated by interferon-β (INF-β), by decreasing the stimulation of anti-inflammatory cytokines such as interleukin-10 (IL-10) and increasing serum inflammatory cytokines such as interleukin-6 (IL-6) and interleukin-1 beta (IL-1β), causing impaired and diminished immune reactions in PD. Moreover, chronic exposure to IL-1β causes an increase in the expression and deposition of -synuclein, as well as increased injury in PD patients.
However, HSV-1 infection induces inefficient production of the antiviral cytokine interferon-lambda (IFN-λ), resulting in HSV-1 reactivation and increased damage to PD patients. Also, the oxidative stress caused by mitochondrial dysfunction promotes viral replication in cells damaged by viral infection, which contributes to the development of Parkinson's disease in patients.
Conclusion: Since the exact cause of Parkinson's disease (PD) is unknown and the prevalence of HSV-1 infection in over 70% of the global population and its lifelong persistence in the olfactory bulb leads to an increasing effect on brain cells in PD, interactions between HSV-1 and host immune and genetic factors can modulate the clinical outcome and severity of PD. Therefore, a greater understanding of the complex relationship between the nature of HSV-1 and its specific immune responses in patients with PD can facilitate the development of effective antiviral therapies and vaccines to prevent the advent of PD.