In the Literature.

Abstract

JC virus (JCV) is the cause of PML, a usually fatal disease for which there is no known effective therapy. Most individuals are infected with JCV during childhood. Infection is life-long and usually asymptomatic, although urinary excretion of the virus is common. Immunocompromise, as in patients with AIDS, may lead to activation of the virus, with the development of a devastating cerebral infection. JCV has tropism for B lymphocytes, kidney epithelial cells, oligodendrocytes, and astrocytes. These cell types have been known to express surface receptors for JCV that are composed of n-linked glycoproteins containing terminal a 2–6linked sialic acid. This receptor alone is, however, insufficient to allow viral entry into the cell. Permissive cells also express a serotonergic receptor, 5HT2AR, that has now been demonstrated to be a functional receptor for JCV and to be required for its entry into the cell. The nonspecific serotonin-receptor antagonists (metoclopramide, chlorpromazine, and clozapine) each significantly inhibited JCV infection of glial cells, a finding duplicated with 5HT2AR-specific antagonists. These findings point toward a novel potential therapeutic approach involving serotonin receptor antagonists for patients with PML. These drugs, a number of which are available and in use for psychiatric and other indications, have the potential advantage of excellent bioavailability within the CNS, as well as excellent tolerability. HIV Resistance Testing