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History and current concepts in the pathogenesis of PML

Eugene O Major1

  • 1Laboratory of Molecular Medicine and Neuroscience, NINDS, Building 10, Room 3B14, 10 Center Drive, MSC 1296, Bethesda, MD 20892-1296, USA. majorg@ninds.nih.gov

Cleveland Clinic Journal of Medicine
|November 30, 2011
PubMed

Insights

The JC virus (JCV) causes progressive multifocal leukoencephalopathy (PML), a rare brain disease. JCV latency in bone marrow CD34+ cells is key to its pathogenesis, especially in immune-altered patients.

Area of Science:

  • Neurovirology
  • Immunology
  • Molecular Biology

Background:

  • Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease caused by the JC virus (JCV).
  • JCV establishes latency in immune cells, with a strong link to bone marrow CD34+ cells.
  • PML emergence in patients on natalizumab and other immune-altering therapies highlights JCV pathogenesis.

Purpose of the Study:

  • To elucidate the role of JCV latency in immune cells and its connection to nervous system infection.
  • To understand the pathogenic mechanisms of JCV infection, particularly in the context of immune suppression.

Main Methods:

  • Analysis of JCV DNA in pathological tissues for PML diagnosis.
  • Investigation of host cell nuclear factors binding to the JCV promoter.
  • Identification of susceptible cell types for JCV lytic infection (oligodendrocytes, astrocytes, immune cells).

Main Results:

  • JCV infection requires specific nuclear binding proteins for viral transcription.
  • Oligodendrocytes, astrocytes, and immune cells (CD34+, CD19+) support JCV lytic infection.
  • Bone marrow CD34+ cells are implicated as the likely site of JCV latency.

Conclusions:

  • JCV latency in bone marrow CD34+ cells is crucial for initiating PML.
  • Understanding JCV's tissue tropism and latency is vital for managing PML in immunocompromised individuals.
  • Immune-altering therapies can reactivate JCV, leading to PML development.

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