Cytotoxicity-Independent Modulation of Amyloid Aggregation by Neurotropic Viruses

Neurotropic viral infections have emerged as potential triggers of protein aggregation in the nervous system. Neurotropic viruses may modulate cellular proteostasis, which can culminate in protein aggregation in the brain, a central event in neurodegeneration. In this contexto, the present study has as objective evaluate whether infection with neurotropic viruses modulates the aggregation of amyloidogenic proteins (Prion and α-synuclein) in human neuroblastoma SH-SY5Y cells. Initially, SH-SY5Y cells were infected with HSV-1, ECHO-30, or EV-A71. Cytotoxicity was assessed through morphological analysis and a MTT reduction assay. Amyloid fibrils and oligomers were detected using dot blot assay, and protein expression levels of PrP and α-syn were analyzed by Western blotting. Dot blot analysis revealed an decrease in amyloid fibril and an increase in amyloid oligomer content following infection with HSV-1 (MOI 0.01) and ECHO-30 (MOI 1). EV-A71 (MOI 0,1) also induced amyloid fibril accumulation in an MOI-dependent manner, without a corresponding change in oligomer levels. Western blot analysis showed that HSV-1 significantly reduced alpha-synuclein expression, an effect not observed with enteroviruses. In contrast, ECHO-30 induced an MOI-dependent increase in Prion protein expression, while EV-A71 and HSV-1 did not alter PrP levels. Our findings suggest that neurotropic viruses can modulate the aggregation and expression of amyloidogenic proteins in neural cells in a cytotoxicity-independent manner. The virus-specific effects observed suggest distinct mechanisms by which infections may influence cellular proteostasis. These results support the hypothesis that viral infections could contribute to the onset or progression of neurodegenerative diseases and highlight the need for further studies to unravel the molecular pathways involved.