title: Human polyomavirus receptor distribution in brain parenchyma contrasts with receptor distribution in kidney and choroid plexus.
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.
authors.affiliation: Department of Molecular Biology, Cell Biology and Biochemistry, Warren Alpert Medical School, Brown University, Providence, Rhode Island.
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Haley
authors.affiliation: Department of Molecular Biology, Cell Biology and Biochemistry, Warren Alpert Medical School, Brown University, Providence, Rhode Island.
authors.forename: Bethany A
authors.initials: BA
authors.lastname: O'Hara
authors.affiliation: Department of Molecular Biology, Cell Biology and Biochemistry, Warren Alpert Medical School, Brown University, Providence, Rhode Island.
authors.forename: Christian D S
authors.initials: CD
authors.lastname: Nelson
authors.affiliation: Department of Molecular Biology, Cell Biology and Biochemistry, Warren Alpert Medical School, Brown University, Providence, Rhode Island.
authors.forename: Frances L P
authors.initials: FL
authors.lastname: Brittingham
authors.affiliation: Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, Rhode Island.
authors.forename: Kammi J
authors.initials: KJ
authors.lastname: Henriksen
authors.affiliation: Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, Rhode Island.
authors.forename: Edward G
authors.initials: EG
authors.lastname: Stopa
authors.affiliation: Department of Molecular Biology, Cell Biology and Biochemistry, Warren Alpert Medical School, Brown University, Providence, Rhode Island. Electronic address: walter_atwood@brown.edu.
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Atwood
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002831:Choroid Plexus / Q000378:metabolism*; D005260:Female; D006801:Humans; D007577:JC Virus; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009836:Oligodendroglia / Q000378:metabolism; D011134:Polysaccharides / Q000378:metabolism*; D044348:Receptors, Serotonin, 5-HT2 / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism*; D012794:Sialic Acids / Q000378:metabolism*
chemical_list: D011134:Polysaccharides; D044348:Receptors, Serotonin, 5-HT2; D011991:Receptors, Virus; D012794:Sialic Acids; C581046:glycan sialylneolacto-N-tetraose c