Exploring JC Polyomavirus Sequences and Human Gene Expression in Brain Tissue of Patients With Progressive Multifocal Leukoencephalopathy

Abstract

Progressive multifocal leukoencephalopathy (PML) is a rare neurological condition associated with reactivation of dormant JC polyomavirus (JCPyV). In this study, we characterized gene expression and JCPyV rearrangements in PML brain tissue. Infection of white matter astrocytes and oligodendrocytes as well as occasional brain cortex neurons was shown. PML brain harbored exclusively rearranged JCPyV variants. Viral transcripts covered the whole genome on both strands. Strong differential expression of human genes associated with neuroinflammation, blood-brain barrier permeability, and neurodegenerative diseases was shown. Pathway analysis revealed wide immune activation in PML brain. The study provides novel insights into the pathogenesis of PML.

Keywords: JC polyomavirus; JCPyV; NGS; PML; brain; neurodegeneration; progressive multifocal leukoencephalopathy; sequencing; transcriptomics; viral transcripts.