Differential distribution of the JC virus receptor-type sialic acid in normal human tissues.
JC virus (JCV), a member of the polyomavirus family, causes a demyelinating disease of the central nervous system (CNS) in humans known as progressive multifocal leukoencephalopathy. Although glial cells are the principal target of JCV productive infection in progressive multifocal leukoencephalopathy patients, little is known regarding the site of JCV persistence and the mechanisms by which the virus spreads to the CNS to cause disease. Previous work has demonstrated the presence of replicating JCV DNA in B lymphocytes from peripheral blood, tonsil, and spleen and it has been hypothesized that lymphocytes may be one site of JCV persistence. Detection of viral gene products in renal tubules and excretion of JC virions in the urine suggests JCV persistence in the kidney. A respiratory route of viral transmission has also been hypothesized implicating the lung as another possible site of persistent JCV infection. Earlier studies from our laboratory have shown that terminal alpha 2,6-linked sialic acid is a critical component of the JCV receptor. In this report we examined the tissue distribution of this JCV receptor-type sialic acid in a panel of normal human tissues. Our results demonstrate that in normal brain JCV receptor-type sialic acids are expressed on oligodendrocytes and astrocytes, but not on cortical neurons. The receptor-type sialic acid is also more highly expressed on B lymphocytes than on T lymphocytes in normal human spleen and tonsil. In addition, both the kidney and lung express abundant levels of alpha 2-6-linked sialic acids. Our data show a striking correlation between the expression of the JCV receptor-type sialic acid on cells and their susceptibility to infection by the virus. These findings also support the hypothesis of JCV persistence in lymphoid tissue and B-cell-facilitated viral dissemination to the CNS.
Eash
Sylvia
S
Department of Molecular Microbiology and Immunology, and Graduate Program in Pathobiology, Rhode Island Hospital, Brown University, Providence, Rhode Island 02912, USA.
Tavares
Rosemarie
R
Stopa
Edward G
EG
Robbins
Scott H
SH
Brossay
Laurent
L
Atwood
Walter J
WJ
D001253:Astrocytes / Q000737:chemistry / Q000378:metabolism; D001402:B-Lymphocytes / Q000737:chemistry / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000378:metabolism; D001923:Brain Chemistry; D004198:Disease Susceptibility; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007577:JC Virus / Q000302:isolation & purification / Q000472:pathogenicity*; D007668:Kidney / Q000737:chemistry / Q000378:metabolism; D008168:Lung / Q000737:chemistry / Q000378:metabolism; D018613:Microscopy, Confocal; D019158:N-Acetylneuraminic Acid / Q000302:isolation & purification* / Q000378:metabolism; D009474:Neurons / Q000737:chemistry / Q000378:metabolism; D009836:Oligodendroglia / Q000737:chemistry / Q000378:metabolism; D014066:Palatine Tonsil / Q000737:chemistry / Q000166:cytology; D027601:Polyomavirus Infections; D011991:Receptors, Virus / Q000302:isolation & purification* / Q000378:metabolism; D013154:Spleen / Q000737:chemistry / Q000378:metabolism; D014412:Tumor Virus Infections
D011991:Receptors, Virus; D019158:N-Acetylneuraminic Acid