JC Virus Infects Neurons and Glial Cells in the Hippocampus.
The human polyomavirus JC (JCV) infects glial cells and is the etiologic agent of the CNS demyelinating disease progressive multifocal leukoencephalopathy. JCV can infect granule cell neurons of the cerebellum, causing JCV granule cell neuronopathy and cortical pyramidal neurons in JCV encephalopathy. Whether JCV also infects neurons in other areas of the CNS is unclear. We determined the prevalence and pattern of JCV infection of the hippocampus in archival samples from 28 patients with known JCV infection of the CNS and 66 control subjects. Among 28 patients, 11 (39.3%) had JCV infection of hippocampus structures demonstrated by immunohistochemistry. Those included gray matter (dentate gyrus and cornu ammonis, subiculum) in 11/11 and afferent or efferent white matter tracts (perforant path, alveus, fimbria) in 10/11. In the hippocampus, JCV infected granule cell and pyramidal neurons, astrocytes, and oligodendrocytes. Although glial cells expressed either JCV regulatory T Antigen or JCV VP1 capsid protein, infected neurons expressed JCV T Antigen only, suggesting an abortive/restrictive infection. None of the 66 control subjects had evidence of hippocampal JCV protein expression by immunohistochemistry or JCV DNA by in situ hybridization. These results greatly expand our understanding of JCV pathogenesis in the CNS.
From the Division of Neuro-Immunology (CW, SB, IJK); Department of Neurology (CW, SB, MPA, IJK); Center for Virology and Vaccine Research, Department of Medicine(CW, SB, IJK); Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts (MPA); and John a. Burns School of Medicine, University of Hawaii, Honolulu, and the Pacific Health Research and Education Institute, Honolulu, Hawaii (LRW).
Christian
C
Wüthrich
From the Division of Neuro-Immunology (CW, SB, IJK); Department of Neurology (CW, SB, MPA, IJK); Center for Virology and Vaccine Research, Department of Medicine(CW, SB, IJK); Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts (MPA); and John a. Burns School of Medicine, University of Hawaii, Honolulu, and the Pacific Health Research and Education Institute, Honolulu, Hawaii (LRW).
Stephanie
S
Batson
From the Division of Neuro-Immunology (CW, SB, IJK); Department of Neurology (CW, SB, MPA, IJK); Center for Virology and Vaccine Research, Department of Medicine(CW, SB, IJK); Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts (MPA); and John a. Burns School of Medicine, University of Hawaii, Honolulu, and the Pacific Health Research and Education Institute, Honolulu, Hawaii (LRW).
Matthew P
MP
Anderson
From the Division of Neuro-Immunology (CW, SB, IJK); Department of Neurology (CW, SB, MPA, IJK); Center for Virology and Vaccine Research, Department of Medicine(CW, SB, IJK); Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts (MPA); and John a. Burns School of Medicine, University of Hawaii, Honolulu, and the Pacific Health Research and Education Institute, Honolulu, Hawaii (LRW).
Lon R
LR
White
From the Division of Neuro-Immunology (CW, SB, IJK); Department of Neurology (CW, SB, MPA, IJK); Center for Virology and Vaccine Research, Department of Medicine(CW, SB, IJK); Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts (MPA); and John a. Burns School of Medicine, University of Hawaii, Honolulu, and the Pacific Health Research and Education Institute, Honolulu, Hawaii (LRW). ikoralni@bidmc.harvard.edu.
Igor J
IJ
Koralnik
Epilepsy; Epilepsy surgery biopsies; Hippocampus; JC virus; JCV encephalopathy (JCVE); JCV granule cell neuronopathy (JCV GCN); Progressive multifocal leukoencephalopathy (PML)