Exploring JC polyomavirus sequences and human gene expression in brain tissue of patients with progressive multifocal leukoencephalopathy

Anni Honkimaa; Pia Laine; Joni Suppula; Olli Tynninen; Mika Saarela; Sini M Laakso; Iivo Hetemäki; Hanna Liimatainen; Petri Auvinen; Eeva Auvinen

doi:10.1093/infdis/jiae066

Exploring JC polyomavirus sequences and human gene expression in brain tissue of patients with progressive multifocal leukoencephalopathy

J Infect Dis. 2024 Feb 14:jiae066. doi: 10.1093/infdis/jiae066. Online ahead of print.

Authors

Affiliations

¹ Department of Virology, Helsinki University Hospital and University of Helsinki, PO Box 21, FI-00014 Helsinki, Finland.
² Institute of Biotechnology, DNA Sequencing and Genomics Laboratory, University of Helsinki, PO Box 56, FI-00014 Helsinki, Finland.
³ Department of Pathology, Helsinki University Hospital and University of Helsinki, PO Box 21, FI-00014 Helsinki, Finland.
⁴ Department of Neurology, Helsinki University Hospital and University of Helsinki, PO Box 21, FI-00014 Helsinki, Finland.
⁵ Translational Immunology Research Program, University of Helsinki, Helsinki, PO Box 21, FI-00014 Helsinki, Finland.

PMID: 38365889
DOI: 10.1093/infdis/jiae066

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