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Measurement of BK-polyomavirus Non-Coding Control Region Driven Transcriptional Activity Via Flow Cytometry
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Sequential changes in the non-coding control region sequences of JC polyomaviruses from the cerebrospinal fluid of

Kazuo Nakamichi1, Shuji Kishida, Kozue Tanaka

  • 1Department of Virology 1, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.

Archives of Virology
|November 10, 2012
PubMed

Insights

JC polyomavirus (JCV) variants in progressive multifocal leukoencephalopathy (PML) change with viral load. New JCV NCCR sequences emerge as PML progresses, but are suppressed when viral load decreases.

Area of Science:

  • Neurovirology
  • Molecular Virology
  • Genetics

Background:

  • Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease of the brain.
  • PML is caused by the JC polyomavirus (JCV), a ubiquitous human virus.
  • JCV isolates from PML patients exhibit genetic diversity, particularly in the non-coding control region (NCCR).

Purpose of the Study:

  • To investigate sequential alterations in JCV NCCR patterns within individual PML patients.
  • To correlate changes in NCCR sequences with JCV viral load dynamics during disease progression and treatment.

Main Methods:

  • Collection of cerebrospinal fluid (CSF) samples from PML patients at multiple time points.
  • Determination of JCV NCCR sequences from CSF isolates.
  • Computer-based analysis of NCCR sequence composition and frequency.

Main Results:

  • In patients with increasing JCV load, dominant NCCR sequences in follow-up CSF samples differed significantly from initial samples.
  • Conversely, stable NCCR patterns were observed in patients whose JCV viral load decreased following therapy.
  • These findings indicate that JCV variants evolve during PML progression.

Conclusions:

  • The emergence of diverse JCV NCCR variants is associated with PML progression.
  • Therapeutic interventions that reduce JCV viral load can suppress the evolution of these viral variants.
  • Understanding NCCR dynamics offers insights into JCV pathogenesis and PML management.

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