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Published on: July 13, 2019
Single-Molecule Sequencing Revealing the Presence of Distinct JC Polyomavirus Populations in Patients With
Hanna Seppälä1, Elina Virtanen1, Mika Saarela2
1Department of Virology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Background:
Progressive multifocal leukoencephalopathy (PML) is a fatal disease caused by reactivation of JC polyomavirus (JCPyV) in immunosuppressed individuals and lytic infection by neurotropic JCPyV in glial cells. The exact content of neurotropic mutations within individual JCPyV strains has not been studied to our knowledge.
Methods:
We exploited the capacity of single-molecule real-time sequencing technology to determine the sequence of complete JCPyV genomes in single reads. The method was used to precisely characterize individual neurotropic JCPyV strains of 3 patients with PML without the bias caused by assembly of short sequence reads.
Results:
In the cerebrospinal fluid sample of a 73-year-old woman with rapid PML onset, 3 distinct JCPyV populations could be identified. All viral populations were characterized by rearrangements within the noncoding regulatory region (NCCR) and 1 point mutation, S267L in the VP1 gene, suggestive of neurotropic strains. One patient with PML had a single neurotropic strain with rearranged NCCR, and 1 patient had a single strain with small NCCR alterations.
Conclusions:
We report here, for the first time, full characterization of individual neurotropic JCPyV strains in the cerebrospinal fluid of patients with PML. It remains to be established whether PML pathogenesis is driven by one or several neurotropic strains in an individual.
Insights
This study fully characterized neurotropic JC polyomavirus (JCPyV) strains in PML patients using single-molecule sequencing. Findings reveal distinct JCPyV populations and mutations, advancing understanding of PML pathogenesis.
Area of Science:
- Virology
- Neuroscience
- Genomics
Background:
- Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease.
- PML is caused by JC polyomavirus (JCPyV) reactivation in immunosuppressed individuals.
- Neurotropic JCPyV strains and their specific mutations in PML remain poorly understood.
Purpose of the Study:
- To precisely characterize individual neurotropic JCPyV strains in PML patients.
- To investigate the genetic makeup of JCPyV strains associated with PML pathogenesis.
- To leverage single-molecule real-time sequencing for comprehensive viral genome analysis.
Main Methods:
- Utilized single-molecule real-time (SMRT) sequencing for complete JCPyV genome sequencing in single reads.
- Analyzed cerebrospinal fluid samples from three PML patients.
- Characterized JCPyV strains without assembly bias from short reads.
Main Results:
- Identified three distinct JCPyV populations in one patient, featuring NCCR rearrangements and S267L VP1 mutation.
- One patient presented a single neurotropic strain with NCCR rearrangements.
- Another patient had a single strain with minor NCCR alterations.
Conclusions:
- This study provides the first full characterization of individual neurotropic JCPyV strains in PML patients' CSF.
- The findings highlight the genetic diversity of JCPyV in PML.
- Further research is needed to determine if PML pathogenesis involves one or multiple neurotropic JCPyV strains.
