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Science 306 (5700): 1380-1383

Copyright © 2004 by the American Association for the Advancement of Science

The Human Polyomavirus, JCV, Uses Serotonin Receptors to Infect Cells

Gwendolyn F. Elphick,1 William Querbes,1,2 Joslynn A. Jordan,1,2 Gretchen V. Gee,1,3 Sylvia Eash,1,2 Kate Manley,1,3 Aisling Dugan,1,2 Megan Stanifer,1,3 Anushree Bhatnagar,4 Wesley K. Kroeze,4 Bryan L. Roth,4 Walter J. Atwood1,2,3*

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 5HT2A receptor antagonists inhibited JCV infection, and monoclonal antibodies directed at 5HT2A receptors blocked infection of glial cells by JCV, but not by SV40. Transfection of 5HT2A receptor–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.

1 Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA.
2 Graduate Program in Pathobiology, Brown University, Providence, RI 02912, USA.
3 Graduate Program in Molecular Biology, Cellular Biology, and Biochemistry, Brown University, Providence, RI 02912, USA.
4 Department of Biochemistry, Case Western Reserve University Medical School, Cleveland, Ohio 44106, USA.

* To whom correspondence should be addressed. E-mail: Walter_Atwood{at}Brown.edu

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