John Cunningham virus (JCV) (JCV)

John Cunningham virus (JCV), also known as human polyomavirus 2, is a small, non-enveloped, double-stranded DNA virus that is highly prevalent in the human population, with 50-90% of adults being seropositive [6, 12, 16]. The virus typically establishes a lifelong latent infection in the kidneys, bone marrow, and lymphoid tissues following an asymptomatic primary infection in childhood [1, 17, 19]. In individuals with severe cellular immunodeficiency—such as those with HIV/AIDS or those receiving potent immunomodulatory therapies like natalizumab—the virus can reactivate and undergo genetic rearrangements in its non-coding control region (NCCR) [13, 17, 18]. This transformation allows the virus to become neurotropic, leading to a lytic infection of oligodendrocytes and astrocytes in the central nervous system, which results in progressive multifocal leukoencephalopathy (PML), a devastating demyelinating disease [2, 4, 22]. Currently, there are no FDA-approved antiviral therapies specifically for JCV; management primarily focuses on restoring the host's immune system, although several drugs like cidofovir, mefloquine, and pembrolizumab have been investigated for their potential to inhibit viral replication or boost the immune response [5, 14, 20].

Other names

JC polyomavirusJCPyVHuman polyomavirus 2JC virus

Inhibition of viral DNA polymerase, antagonism of the 5-HT2A receptor to block viral entry, immune checkpoint inhibition to enhance T-cell mediated viral clearance, and inhibition of viral DNA replication.