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

Gwendolyn F Elphick1, William Querbes, Joslynn A Jordan

  • 1Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA.

Science (New York, N.Y.)
|November 20, 2004
PubMed

Insights

The serotonin 5HT2A receptor is the cellular entry point for the John Cunningham virus (JCV), which causes progressive multifocal leukoencephalopathy. Blocking this receptor may treat this fatal brain disease.

Area of Science:

  • Neurovirology
  • Molecular and Cellular Biology
  • Immunology

Background:

  • Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease caused by the John Cunningham virus (JCV) in immunocompromised individuals.
  • Identifying the cellular receptor for JCV is crucial for understanding viral entry and developing therapeutic strategies.

Purpose of the Study:

  • To identify the cellular receptor used by JCV for entry into human glial cells.
  • To investigate the potential of targeting this receptor for therapeutic intervention against PML.

Main Methods:

  • Utilized 5HT2A receptor antagonists and monoclonal antibodies to block JCV infection.
  • Performed transfection experiments with 5HT2A receptor-negative cells.
  • Employed tagged 5HT2A receptors and labeled JCV to track viral internalization and localization.

Main Results:

  • The serotonin 5HT2A receptor (5HT2AR) was identified as the cellular receptor for JCV on human glial cells.
  • 5HT2A receptor antagonists and antibodies significantly inhibited JCV infection.
  • Transfection of 5HT2A receptor-negative cells with 5HT2AR restored JCV infectivity, which was then blocked by antibodies.
  • Internalized JCV colocalized with 5HT2A receptors in endosomal compartments.

Conclusions:

  • The 5HT2A receptor is essential for JCV entry into human glial cells.
  • Targeting the 5HT2A receptor with antagonists or antibodies shows promise for treating progressive multifocal leukoencephalopathy.

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