Interaction Between Coxsackievirus B3 Infection and α-Synuclein in Parkinson’s Disease

Abstract BackgroundParkinson's disease (PD) is one of the most common neurodegenerative disease. PD is pathologically characterized by the death of midbrain dopaminergic neurons and the accumulation of intracellular protein inclusions called Lewy bodies or Lewy neurites. The major component of Lewy bodies is α-synuclein (α-syn). Prion-like propagation of α-syn has emerged as a novel mechanism in the progression of PD. Targeting this mechanism could enable the development of disease-modifying therapies for patients with PD. Nevertheless, the initial triggers of LB formation leading to acceleration of the process remain elusive.MethodsTo evaluate α-syn function in viral replication, we infected coxsackievirus B3 (CVB3) to α-syn overexpressed neurons or α-syn transgenic (TG) mice. We then performed biochemical and histological analyses to evaluate interaction between CVB3 and α-syn in Lewy body formation.ResultsWe demonstrated that CVB3 infection can induce α-syn-associated inclusion body formation in neurons as a trigger. The inclusion bodies contained clustered organelles, including damaged mitochondria with α-syn fibrils. α-Syn overexpression accelerated inclusion body formation and induced more concentric inclusion bodies. In brains from CVB3 infected mice, α-syn aggregates in the cell body of midbrain neurons were observed. Additionally, α-syn overexpression favored CVB3 replication and related cytotoxicity. α-Syn transgenic mice had a low survival rate, enhanced CVB3 replication, and further neuronal cell death, including dopaminergic neurons in the substantia nigra. These results may be due to the different usage of autophagy between CVB3 and α-syn. ConclusionsThis study elucidated the mechanism of Lewy body formation and the pathogenesis of PD associated with CVB3 infection.