JC Virus Infects Neurons and Glial Cells in the Hippocampus

Area of Science:

• Neurovirology
• Central Nervous System (CNS) Pathology
• Human Polyomaviruses

Background:

• Human polyomavirus JC (JCV) is known to infect glial cells, causing progressive multifocal leukoencephalopathy (PML).
• JCV infection has been observed in cerebellar granule cell neurons and cortical pyramidal neurons.
• The extent of JCV infection in other CNS neuronal populations, particularly the hippocampus, remains largely uncharacterized.

Purpose of the Study:

• To investigate the prevalence and patterns of JCV infection within the human hippocampus.
• To determine which cell types in the hippocampus are susceptible to JCV infection.
• To elucidate the nature of JCV infection in hippocampal neurons.

Main Methods:

• Archival hippocampal tissue samples from 28 patients with known CNS JCV infection and 66 control subjects were analyzed.
• Immunohistochemistry was employed to detect JCV proteins (T Antigen and VP1 capsid protein).
• In situ hybridization was used to detect JCV DNA.

Main Results:

• JCV infection was detected in hippocampal structures in 11 out of 28 (39.3%) patients.
• Infected areas included gray matter (dentate gyrus, cornu ammonis, subiculum) and white matter tracts (perforant path, alveus, fimbria).
• JCV infected hippocampal neurons (granule and pyramidal), astrocytes, and oligodendrocytes; neurons exclusively expressed T Antigen, suggesting a restrictive infection.

Conclusions:

• JCV infects hippocampal neurons and glial cells, significantly expanding the known tropism of JCV within the CNS.
• The distinct expression of JCV proteins in infected neurons suggests a unique, possibly abortive, replication cycle in these cells.
• These findings enhance the understanding of JCV pathogenesis and its potential impact on hippocampal function.