Progressive multifocal leukoencephalopathy (PML) is caused by JC polyomavirus reactivation. Which CNS cell type is productively infected, causing the hallmark cytopathic changes seen on histology?

• A Neurons — showing cytoplasmic Cowdry A inclusions and axonal degeneration
• B Microglia — forming multinucleated giant cells with cytomegalic nuclear inclusions
• C Astrocytes — showing homogeneous nuclear 'owl-eye' inclusions causing reactive astrogliosis
• D Oligodendrocytes — showing viral nuclear inclusion bodies and apoptotic death causing demyelination, with bizarre astrocytes nearby ✓

Explanation

JC virus productively infects oligodendrocytes (which express the receptor serotonin 5-HT2A and the co-receptor agnoprotein-binding gangliosides), causing viral replication with characteristic enlarged, hyperchromatic nuclei containing amphophilic viral inclusion bodies. Oligodendrocyte death destroys the myelin sheaths they maintain, producing multifocal demyelination without axon destruction. Nearby reactive astrocytes become bizarrely enlarged with hyperchromatic irregular nuclei ('bizarre astrocytes'), sometimes mistaken for neoplasia. Cytomegalovirus produces owl-eye inclusions in any cell type; JC-infected astrocytes show only reactive changes, not productive infection.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.