Human coronaviruses in idiopathic Parkinson's disease: Implications of SARS-CoV-2's modulation of the host's transcriptome.

Abstract

ObjectiveA recent study on the effects of SARS-CoV-2 infection on the host's transcriptome indicated the perturbation of several pathways associated with neurodegeneration, including but not limited to Parkinson's and Huntington's diseases. The purpose of this study was to determine overlapping pathways between iPD vs. Controls and those associated with SARS-CoV-2 infection.MethodsGene set enrichment analyses (GSEA) were performed on gene expression data from tissues donated by idiopathic Parkinson's disease patients (iPD). These included dorsal motor nucleus of the vagus (DMNV), substantia nigra (SN), whole blood (WB) and peripheral blood mononuclear cell samples (PBMC). Enriched pathways detected by GSEA results were subsequently compared to (a) those retrieved by two independently constructed SARS-CoV-2 – host interactomes, as well as (b) previously published pathway data. For all analyses, a false discovery rate (FDR) <0.05 was considered statistically significant.ResultsAnalysis of iPD data revealed multiple immune response and viral parasitism -related pathways (FDR < 0.05). Head-to-head comparisons as well as confirmatory analyses revealed several pathways and gene ontology (GO) terms overlapping between iPD tissues and SARS-CoV-2 induced transcriptomic changes: “Parkinson's Disease” and “Huntington's Disease” (overlapping in DMNV, ION, SN, and WB; FDR < 0.05), “NAFLD” (overlapping in DMNV, SN, PBMC and WB; FDR < 0.05), mRNA surveillance and proteostasis pathways (All datasets; FDR < 0.5), among others.ConclusionThe overlap noted in this comparative transcriptomic study outlines the potential contribution of human coronaviruses in the pathogenesis of iPD. Furthermore, given SARS-CoV-2's neuroinvasive potential, closer scrutiny is warranted towards its contribution in the long-term development of neurodegenerative disease.