Progressive multifocal leukoencephalopathy (PML) affects immunosuppressed patients, especially those with AIDS or on natalizumab. The causative virus and its target cell type in the CNS are:
- A CMV infecting endothelial cells and causing vasculitis
- B HSV-1 infecting neurons via trigeminal ganglion reactivation
- C JC virus (John Cunningham polyomavirus) infecting and lysing oligodendrocytes, causing demyelination ✓
- D EBV infecting astrocytes, causing primary CNS lymphoma
Explanation
PML is caused by JC polyomavirus, which establishes latent infection in kidneys and B lymphocytes in the general population (~80% seropositivity). Immunosuppression allows viral reactivation and hematogenous spread to the CNS, where the virus selectively infects oligodendrocytes (using their serotonin receptor 5-HT2A and LSTc receptor as entry receptors). Infected oligodendrocytes show characteristic enlarged nuclei with ground-glass chromatin on histology, then undergo lysis, causing focal demyelinating lesions. Bizarre enlarged astrocytes are a secondary finding. Natalizumab (anti-α4 integrin) prevents CNS immune surveillance, enabling JC reactivation.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.