The human polyomavirus, JCV, uses serotonin receptors to infect cells Public Deposited

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  • Gee, Gretchen V.
    • Other Affiliation: Department of Molecular Microbiology and Immunology and Graduate Program in Molecular Biology, Cellular Biology, and Biochemistry, Brown University, Providence, RI 02912, USA
  • Atwood, Walter J.
    • Other Affiliation: Department of Molecular Microbiology and Immunology, Graduate Program in Pathobiology, and Graduate Program in Molecular Biology, Cellular Biology, and Biochemistry, Brown University, Providence, RI 02912, USA
  • Eash, Sylvia
    • Other Affiliation: Department of Molecular Microbiology and Immunology and Graduate Program in Pathobiology, Brown University, Providence, RI 02912, USA
  • Bhatnagar, Anushree
    • Other Affiliation: Department of Biochemistry, Case Western Reserve University Medical School, Cleveland, Ohio 44106, USA
  • Querbes, William
    • Other Affiliation: Department of Molecular Microbiology and Immunology and Graduate Program in Pathobiology, Brown University, Providence, RI 02912, USA
  • Kroeze, Wesley K.
    • Other Affiliation: Department of Biochemistry, Case Western Reserve University Medical School, Cleveland, Ohio 44106, USA
  • Manley, Kate
    • Other Affiliation: Department of Molecular Microbiology and Immunology and Graduate Program in Molecular Biology, Cellular Biology, and Biochemistry, Brown University, Providence, RI 02912, USA
  • Jordan, Joslynn A.
    • Other Affiliation: Department of Molecular Microbiology and Immunology and Graduate Program in Pathobiology, Brown University, Providence, RI 02912, USA
  • Roth, Bryan L.
    • ORCID: https://orcid.org/0000-0002-0561-6539
    • Other Affiliation: Department of Biochemistry, Case Western Reserve University Medical School, Cleveland, Ohio 44106, USA
  • Dugan, Aisling
    • Other Affiliation: Department of Molecular Microbiology and Immunology and Graduate Program in Pathobiology, Brown University, Providence, RI 02912, USA
  • Stanifer, Megan
    • Other Affiliation: Department of Molecular Microbiology and Immunology and Graduate Program in Molecular Biology, Cellular Biology, and Biochemistry, Brown University, Providence, RI 02912, USA
  • Elphick, Gwendolyn F.
    • Other Affiliation: Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA
Abstract
  • The human polyomavirus, JCV, causes the fatal demyelinating disease progressive multifocal leukoencephalopathy in immunocompromised patients. We found that the serotonergic receptor 5HT2AR could act as the cellular receptor for JCV on human glial cells. The 5HT2Areceptor antagonists inhibited JCV infection, and monoclonal antibodies directed at 5HT2Areceptors blocked infection of glial cells by JCV, but not by SV40. Transfection of 5HT2Areceptor–negative HeLa cells with a 5HT2A receptor rescued virus infection, and this infection was blocked by antibody to the 5HT2A receptor. A tagged 5HT2A receptor colocalized with labeled JCV in an endosomal compartment following internalization. Serotonin receptor antagonists may thus be useful in the treatment of progressive multifocal leukoencephalopathy.
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Resource type
  • Article
Rights statement
  • In Copyright
Journal title
  • Science
Journal volume
  • 306
Journal issue
  • 5700
Page start
  • 1380
Page end
  • 1383
Language
  • English
Version
  • Postprint
ISSN
  • 0036-8075
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