Journal
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
Volume 68, Issue 1, Pages 15-25Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/NEN.0b013e3181912570
Keywords
Cerebellum; Granule cell neurons; HIV; JC virus; Progressive multifocal leukoencephalopathy
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Funding
- National Institutes of Health to Igor Koralnik. MD [R21 NS 051124, ROI NS 047029, 041198, K24 NS 060950]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [P30AI042853] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [U01MH083545, R24MH059724, R24MH059745] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS041198, R01NS047029, R24NS038841, R21NS051124, K24NS060950] Funding Source: NIH RePORTER
- Medical Research Council [G0500863] Funding Source: researchfish
- MRC [G0500863] Funding Source: UKRI
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Progressive multifocal leukoencephalopathy (PML) occurs, most often in immunosuppressed individuals. The lesions of PML result from astrocyte and oligodendrocyte infection by the polyomavirus JC (JCV): JCV has also been shown to infect and destroy cerebellar granule cell neurons (GCNs) in 2 human immunodeficiency virus (HIV)-positive patients. To determine the prevalence and pattern of JCV infection in GCNs, we immunostained formalin-fixed paraffin-embedded cerebellar samples from 40 HIV-positive and 3 HIV-negative PML patients for JCV, and glial and neuronal markers. The JCV infection was detected in 30 patients (70%); 28 (93%) of them had JCV-infected cells in the GC layer: JCV-infected GCNs were demonstrated in 15 (79%) of 19 tested cases, The JCV regulatory T antigen was expressed more frequently and abundantly in GCNs than JCV VP1 capsid protein. None of 37 HIV-negative controls but 1 (3%) of 35 HIV-positive subjects without PML had distinct foci of JCV-intected GCNs. Thus, JCV infection of GCNs is frequent in PML patients and may occur in the absence of cerebellar white matter demyelinating lesions. The predominance of T antigen over VP1 expression in GCNs suggests that they may be the site of early or latent central nervous system JCV infection. These results indicate that infection of GCNs is all important, previously overlooked. aspect of JCV pathogenesis in immunosuppressed individuals.
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