JC Polyomavirus Abundance and Distribution in Progressive Multifocal Leukoencephalopathy (PML) Brain Tissue

Keith A Wharton1, Catherine Quigley1, Marian Themeles1

  • 1Translational Pathology Laboratory, Biogen Inc., Cambridge, MA, United States of America.

Plos One
|May 19, 2016
PubMed

Insights

JC polyomavirus (JCV) can cause progressive multifocal leukoencephalopathy (PML). This study found JCV spreads along myelin sheaths, potentially explaining axonal destruction in PML patients.

Area of Science:

  • Neurovirology
  • Immunology
  • Neuropathology

Background:

  • JC polyomavirus (JCV) infection is common, but progressive multifocal leukoencephalopathy (PML) is rare, typically in immunosuppressed individuals.
  • PML is an emerging drug safety concern linked to immunomodulatory therapies, including efalizumab.

Purpose of the Study:

  • To investigate the relationship between JCV life cycle and PML pathology.
  • To analyze viral evolution and spread in PML brain tissue from an efalizumab-treated patient.

Main Methods:

  • Histopathology and quantitative genomic, proteomic, and molecular localization analyses of autopsy brain tissue.
  • Sequence analysis of regulatory DNA, VP1, VP2, and agnoprotein in lesional brain tissue.

Main Results:

  • Identified PML-associated mutations in JCV regulatory DNA, VP1, and agnoprotein, plus novel VP2 mutations, indicating viral evolution.
  • Observed a strong correlation between demyelination, axonal destruction, and JCV dispersion along white matter myelin sheaths.
  • Findings were consistent with a similar case in an immunocompromised rhesus macaque.

Conclusions:

  • JCV undergoes significant evolution within PML lesions.
  • Long-range spread of JCV and axonal destruction in PML may involve extracellular association with the white matter myelin sheath.

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