Interaction between coxsackievirus B3 infection and α-synuclein in models of Parkinson's disease

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. 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 alpha-synuclein (alpha-syn). Prion-like propagation of alpha-syn has emerged as a novel mechanism in the progression of PD. This mechanism has been investigated to reveal factors that initiate Lewy pathology with the aim of preventing further progression of PD. Here, we demonstrate that coxsackievirus B3 (CVB3) infection can induce alpha-syn-associated inclusion body formation in neurons which might act as a trigger for PD. The inclusion bodies contained clustered organelles, including damaged mitochondria with alpha-syn fibrils. alpha-Syn overexpression accelerated inclusion body formation and induced more concentric inclusion bodies. In CVB3-infected mice brains, alpha-syn aggregates were observed in the cell body of midbrain neurons. Additionally, alpha-syn overexpression favored CVB3 replication and related cytotoxicity. alpha-Syn transgenic mice had a low survival rate, enhanced CVB3 replication, and exhibited neuronal cell death, including that of dopaminergic neurons in the substantia nigra. These results may be attributed to distinct autophagy-related pathways engaged by CVB3 and alpha-syn. This study elucidated the mechanism of Lewy body formation and the pathogenesis of PD associated with CVB3 infection.

Automated summary

This study elucidated the mechanism of Lewy body formation and the pathogenesis of PD associated with CVB3 infection. CVB3 infection can induce α-syn-associated inclusion body formation in neurons, acting as a trigger for PD. α-Syn overexpression in CVB3-infected mice brains favored virus replication, leading to neuronal cell death and a low survival rate.