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06:44
Isolation of Brain-infiltrating Leukocytes
Published on: June 13, 2011
The pathogenesis of progressive multifocal leukoencephalopathy.
Joseph R Berger1, Kamel Khalili
1Department of Neurology, University of Kentucky, 740 S. Limestone St., Lexington, Kentucky 40536, USA. joseph.berger@uky.edu
Discovery Medicine
|December 30, 2011
Summary
Progressive multifocal leukoencephalopathy (PML) pathogenesis is linked to JC virus reactivation in immunocompromised individuals, particularly those with HIV or on certain therapies. Understanding JC virus acquisition and neurotropism is key to preventing PML.
Area of Science:
- Neurovirology
- Immunology
Background:
- Progressive multifocal leukoencephalopathy (PML) risk is elevated in HIV infection and with newer therapies like natalizumab.
- JC virus, the causative agent, is ubiquitous, but PML develops rarely, suggesting specific immune or viral factors are involved.
Purpose of the Study:
- To outline the known facts and unanswered questions regarding the pathogenesis of progressive multifocal leukoencephalopathy (PML).
- To hypothesize the acquisition and replication pathway of JC virus leading to PML.
Main Methods:
- Review of existing literature on PML, JC virus, and associated risk factors.
- Analysis of clinical observations regarding disease onset, immune status, and therapeutic interventions.
Main Results:
- JC virus is ubiquitous, often acquired orally, and shed in urine.
- Impaired cell-mediated immunity, not innate immunity, increases PML risk.
- A latency period is observed after natalizumab/efalizumab treatment, and immune restoration can halt PML progression.
Conclusions:
- PML pathogenesis likely involves a neurotropic JC virus form that replicates in glial cells during impaired immunosurveillance.
- Key questions remain about viral acquisition, tissue tropism, neurotropic form origin, brain entry, and CNS immunosurveillance roles.
- The absence of an animal model hinders research into PML pathogenesis.
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