JC polyomavirus: a short review of its biology, its association with progressive multifocal leukoencephalopathy, and the diagnostic value of different methods to manifest its activity or presence

ABSTRACT

Introduction

JC polyomavirus is the causative agent of progressive multifocal leukoencephalopathy (PML), a demyelinating disease resulting from the lytic infection of oligodendrocytes that may develop in immunosuppressed individuals: HIV1 infected or individuals under immunosuppressive therapies. Understanding the biology of JCPyV is necessary for a proper patient management, the development of diagnostic tests, and risk stratification.

Areas covered

The review covers different areas of expertise including the genomic characterization of JCPyV strains detected in different body compartments (urine, plasma, and cerebrospinal fluid) of PML patients, viral mutations, molecular diagnostics, viral miRNAs, and disease.

Expert opinion

The implementation of molecular biology techniques improved our understanding of JCPyV biology. Deep sequencing analysis of viral genomes revealed the presence of viral quasispecies in the cerebrospinal fluid of PML patients characterized by noncoding control region rearrangements and VP1 mutations. These neurotropic JCPyV variants present enhanced replication and an altered cell tropism that contribute to PML development. Monitoring these variants may be relevant for the identification of patients at risk of PML. Multiplex realtime PCR targeting both the LTAg and the archetype NCCR could be used to identify them. Failure to amplify NCCR should indicate the presence of a JCPyV prototype speeding up the diagnostic process.

KEYWORDS:

• CSF
• JCPyV
• NCCR rearrangements
• PML
• Realtime PCR
• VP1 mutations
• viral quasispecies

Article highlights

• JCPyV is the causative agent of progressive multifocal leukoencephalopathy (PML)

• Subjects with profound immunodeficiency or under immune suppressive treatment are at risk of developing PML

• Detection of JCPyV DNA by real-time PCR in CSF is diagnostic when combined with typical clinical and radiological findings

• Deep-sequencing analysis of NCCR region is important for the detection of NCCR rearrangements and identification of neurotropic JCPyV variants

• VP1 mutations can be found associated to NCCR rearrangements

• Neurotropic variants present enhanced replication and altered cell tropism that contribute to PML development

• JCPyV miRNA levels might predict the risk of PML development

• The combined use of the above-mentioned molecular tools should improve the diagnostic process and help identifying patients at risk of PML development as compared to the only measurement of anti-JCPyV antibodies

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewers Disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.