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Progressive multifocal leukoencephalopathy: Dot-shaped inclusions and virus-host interactions.

Yukiko Shishido-Hara1,2

  • 1Department of Pathology, School of Medicine, Kyorin University, Tokyo, Japan.

Neuropathology : Official Journal of the Japanese Society of Neuropathology
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Summary

Progressive multifocal leukoencephalopathy (PML) pathology is evolving due to complex virus-host interactions. New findings reveal intranuclear viral inclusions and variable immune responses impacting PML disease progression and prognosis.

Keywords:
IRISJC virusPMLnatalizumabprogressive multifocal leukoencephalopathy

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Area of Science:

  • Neurology
  • Virology
  • Pathology

Background:

  • Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease caused by human polyomavirus JC (JC virus) reactivation.
  • JC virus typically reactivates in immunocompromised individuals, leading to varied inflammatory responses.
  • The pathology of PML is becoming more complex due to viral virulence and host immunity dynamics.

Purpose of the Study:

  • To review the evolving pathology of PML.
  • To focus on the intranuclear targets of JC virus infection.
  • To examine host inflammatory reactions in PML.

Main Methods:

  • Review of existing literature on PML pathology.
  • Analysis of histopathological findings, including HE staining and immunohistochemistry.
  • Examination of JC virus-host interactions and immune responses.

Main Results:

  • PML pathology includes both full and dot-shaped intranuclear viral inclusions, indicating different stages of infection.
  • Host immune status significantly influences PML presentation and prognosis, with variable anti-viral responses observed.
  • Immune reconstitution inflammatory syndrome (IRIS) can paradoxically worsen PML following immune recovery.

Conclusions:

  • PML pathology is diversifying, characterized by distinct intranuclear viral inclusion patterns.
  • Understanding the spectrum of host immune responses is crucial for managing PML.
  • Further research is needed to clarify mechanisms like IRIS in PML pathogenesis.