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

Abstract

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 α-synuclein (α-syn). Prion-like propagation of α-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 α-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 α-syn fibrils. α-Syn overexpression accelerated inclusion body formation and induced more concentric inclusion bodies. In CVB3-infected mice brains, α-syn aggregates were observed in the cell body of midbrain neurons. Additionally, α-syn overexpression favored CVB3 replication and related cytotoxicity. α-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 α-syn. This study elucidated the mechanism of Lewy body formation and the pathogenesis of PD associated with CVB3 infection.

Identification of key genes and signaling pathways associated with dementia with Lewy bodies and Parkinson's disease dementia using bioinformatics

“…Coxsackievirus B3 infection can induce α-synuclein-associated inclusion body formation in neurons, which might act as a trigger for PD. Transgenic mice that express α-synuclein showed enhanced Coxsackievirus B3 replication and exhibited dopaminergic neuronal death in the substantia nigra ( 30 ). A B-cell receptor signaling pathway and one carbon pool by folate signaling pathways were positively correlated with the DLB subset.…”

Picornavirus May Be Linked to Parkinson’s Disease through Viral Antigen in Dopamine-Containing Neurons of Substantia Nigra

“…The role of the neuronal expression of alpha-synuclein is still unknown, but there is data suggesting alpha-synuclein expression in neurons is a restriction factor, inhibiting viral replication in the CNS [ 69 ]. In contrast, a recent study demonstrated that alpha-synuclein enhanced picornavirus replication in an experimentally infected PD mouse model, resulting in lower survival rate [ 70 ].…”

Enterovirus infection and its relationship with neurodegenerative diseases

“…Indeed, a recent study found that α-synuclein is up-regulated and associated with α-synuclein inclusion body formation and dysfunctional autophagy machinery in neurons during coxsackievirus B3 (CVB3) infection. 51 Additionally, the authors observed α-synuclein aggregates in the cell body of midbrain neurons of mice infected with CVB3. 51 These modifications might act as triggers for PD.…”