Human polyomavirus receptor distribution in brain parenchyma contrasts with receptor distribution in kidney and choroid plexus.
Title | Human polyomavirus receptor distribution in brain parenchyma contrasts with receptor distribution in kidney and choroid plexus. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Haley, SA, O'Hara, BA, Nelson, CDS, Brittingham, FLP, Henriksen, KJ, Stopa, EG, Atwood, WJ |
Journal | Am J Pathol |
Volume | 185 |
Issue | 8 |
Pagination | 2246-58 |
Date Published | 2015 Aug |
ISSN | 1525-2191 |
Keywords | Adult, Aged, Aged, 80 and over, Astrocytes, Brain, Choroid Plexus, External, Female, Humans, JC Virus, Kidney, Male, Middle Aged, Oligodendroglia, Polysaccharides, Receptors, Serotonin, 5-HT2, Receptors, Virus, Sialic Acids |
Abstract | The human polyomavirus, JCPyV, is the causative agent of progressive multifocal leukoencephalopathy, a rare demyelinating disease that occurs in the setting of prolonged immunosuppression. After initial asymptomatic infection, the virus establishes lifelong persistence in the kidney and possibly other extraneural sites. In rare instances, the virus traffics to the central nervous system, where oligodendrocytes, astrocytes, and glial precursors are susceptible to lytic infection, resulting in progressive multifocal leukoencephalopathy. The mechanisms by which the virus traffics to the central nervous system from peripheral sites remain unknown. Lactoseries tetrasaccharide c (LSTc), a pentasaccharide containing a terminal α2,6-linked sialic acid, is the major attachment receptor for polyomavirus. In addition to LSTc, type 2 serotonin receptors are required for facilitating virus entry into susceptible cells. We studied the distribution of virus receptors in kidney and brain using lectins, antibodies, and labeled virus. The distribution of LSTc, serotonin receptors, and virus binding sites overlapped in kidney and in the choroid plexus. In brain parenchyma, serotonin receptors were expressed on oligodendrocytes and astrocytes, but these cells were negative for LSTc and did not bind virus. LSTc was instead found on microglia and vascular endothelium, to which virus bound abundantly. Receptor distribution was not changed in the brains of patients with progressive multifocal leukoencephalopathy. Virus infection of oligodendrocytes and astrocytes during disease progression is LSTc independent. |
DOI | 10.1016/j.ajpath.2015.04.003 |
Alternate Journal | Am J Pathol |
PubMed ID | 26056932 |
PubMed Central ID | PMC4530127 |
Grant List | U24 MH100929 / MH / NIMH NIH HHS / United States U01 MH083507 / MH / NIMH NIH HHS / United States R24 MH059724 / MH / NIMH NIH HHS / United States P01NS065719 / NS / NINDS NIH HHS / United States P30GM103410 / GM / NIGMS NIH HHS / United States U01 MH083500 / MH / NIMH NIH HHS / United States P01 NS065719 / NS / NINDS NIH HHS / United States U0MH083507 / MH / NIMH NIH HHS / United States R24 NS045491 / NS / NINDS NIH HHS / United States U24 MH100928 / MH / NIMH NIH HHS / United States R24MH59724 / MH / NIMH NIH HHS / United States R24 MH059745 / MH / NIMH NIH HHS / United States R24MH59745 / MH / NIMH NIH HHS / United States R01NS043097 / NS / NINDS NIH HHS / United States R24NS45491 / NS / NINDS NIH HHS / United States P30 GM103410 / GM / NIGMS NIH HHS / United States R01 NS043097 / NS / NINDS NIH HHS / United States U01MH083501 / MH / NIMH NIH HHS / United States U01 MH083501 / MH / NIMH NIH HHS / United States U01 MH083506 / MH / NIMH NIH HHS / United States U0MH083506 / MH / NIMH NIH HHS / United States |