JC polyomavirus neuroinvasion across the blood-brain barrier: Current understanding and emerging perspectives

Area of Science:

• Neurovirology
• Immunology
• Cell Biology

Background:

• JC Polyomavirus (JCPyV) is the etiological agent of progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease.
• PML diagnosis often follows irreversible neuropathology, highlighting the need to understand JCPyV neuroinvasion mechanisms.
• The blood-brain barrier (BBB) is a critical interface for JCPyV entry into the central nervous system.

Purpose of the Study:

• To review potential pathways for JCPyV traversal across the BBB.
• To elucidate mechanisms of JCPyV neuroinvasion.
• To discuss limitations in current in vitro BBB models for studying JCPyV.

Main Methods:

• Review of existing literature on JCPyV, PML, and BBB function.
• Analysis of JCPyV DNA presence in vascular endothelium of PML patients.
• Exploration of three proposed JCPyV BBB crossing mechanisms: diapedesis, paracellular passage, and transcytosis.

Main Results:

• JCPyV DNA is detected in the vascular endothelium of postmortem brain tissue from PML patients.
• Demyelinating lesions in PML often occur near vascularized areas, suggesting a vascular route of entry.
• Three potential JCPyV neuroinvasion pathways across the BBB are identified: "Trojan Horse" diapedesis, paracellular passage, and transcytosis.

Conclusions:

• Understanding JCPyV neuroinvasion pathways is key to comprehending PML pathogenesis before irreversible damage.
• Further research into JCPyV-BBB interactions is needed to develop preventative or therapeutic strategies.
• Improved in vitro BBB models are required to accurately simulate JCPyV neuroinvasion dynamics.