Progressive multifocal leukoencephalopathy (PML) is caused by JC virus reactivation in immunocompromised patients. Which cell types are preferentially infected, and what is the pathological consequence of this tropism?

• A JC virus infects microglial cells, causing lytic infection that destroys the innate immune surveillance of white matter, allowing secondary oligodendrocyte dysfunction
• B JC virus infects neurons selectively in the cortical grey matter, causing progressive cortical neuronal loss without white matter involvement
• C JC virus infects oligodendrocytes (which express the 5-HT2A serotonin receptor as the entry receptor) and astrocytes; lytic infection of oligodendrocytes destroys myelin-producing cells, causing demyelination; infected astrocytes show bizarre enlargement (non-lytic infection) appearing as giant, bizarre astrocytes on pathology ✓
• D JC virus infects CD4+ T-cells in the white matter perivascular spaces, causing T-cell depletion and secondary demyelination via immune deficiency

Explanation

JC virus (a polyomavirus) uses the 5-HT2A serotonin receptor as its primary cellular entry receptor and LSTc (lactoseries tetrasaccharide c) as co-receptor. It has two distinct infection patterns in the CNS: (1) lytic infection of oligodendrocytes — progressive destruction of myelin-producing cells causing confluent asymmetric demyelination with relative axonal sparing, the hallmark white matter lesions of PML; (2) non-lytic productive infection of astrocytes — causing marked nuclear enlargement with bizarre, hyperchromatic, pleomorphic nuclei that can mimic glioma cells on histology. Microglial cells show characteristic JC-infected appearance as 'foamy' cells. Neuronal and T-cell tropism are not the primary targets in PML.

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

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Written and medically reviewed by the StethoPrep medical team.