Available online 12 February 2024, 105652

PML patients frequently harbor JCPyV strains with rearranged NCCR in the brain

JCPyV with archetype or rearranged NCCR can be found in the CNS of non-PML patients

Sensitive PCR and NGS can detect and differentiate highly pathogenic JCPyV strains

Monitoring for emerging JCPyV with rearranged NCCR may improve PML risk assessment

JC polyomavirus (JCPyV) persists asymptomatic in more than half of the human population. Immunocompromising conditions may cause reactivation and acquisition of neurotropic rearrangements in the viral genome, especially in the non-coding control region (NCCR). Such rearranged JCPyV strains are strongly associated with the development of progressive multifocal leukoencephalopathy (PML).

Using next-generation sequencing (NGS) and bioinformatics tools, the NCCR was characterized in cerebrospinal fluid (CSF; N=21) and brain tissue (N=16) samples from PML patients (N=25), urine specimens from systemic lupus erythematosus patients (N=2), brain tissue samples from control individuals (N=2) and waste-water samples (N=5). Quantitative PCR was run in parallel for diagnostic PML samples.

Archetype NCCR (i.e. ABCDEF block structure) and archetype-like NCCR harboring minor mutations were detected in two CSF samples and in one CSF sample and in one tissue sample, respectively. Among samples from PML patients, rearranged NCCRs were found in 8 out of 21 CSF samples and in 14 out of 16 brain tissue samples. Complete or partial deletion of the C and D blocks was characteristic of most rearranged JCPyV strains. From ten CSF samples and one tissue sample NCCR could not be amplified.

Rearranged NCCRs are predominant in brain tissue and common in CSF from PML patients. Extremely sensitive detection and identification of neurotropic viral populations in CSF or brain tissue by NGS may contribute to early and accurate diagnosis, timely intervention and improved patient care.

diagnostics

JC polyomavirus

NGS

PML

targeted sequencing

© 2024 The Authors. Published by Elsevier B.V.