John Cunningham virus (JC virus) (JCV)

The John Cunningham virus (JCV) is a ubiquitous human polyomavirus that typically establishes a lifelong, asymptomatic latent infection in the kidneys, bone marrow, and lymphoid tissues of 50-70% of the adult population (NINDS, 2023). In the setting of severe immunosuppression—often due to HIV/AIDS, hematological malignancies, or the use of immunomodulatory therapies like natalizumab—the virus can reactivate, mutate, and migrate to the central nervous system. Once in the brain, JCV selectively infects and destroys oligodendrocytes and astrocytes, leading to progressive multifocal leukoencephalopathy (PML), a rapidly progressing and frequently fatal demyelinating disease (StatPearls, 2023). Targeting JCV infected cells is a significant clinical challenge as there are currently no FDA-approved antiviral therapies specific to the virus. Experimental treatments focus on interfering with viral entry via the 5-HT2A receptor or utilizing immune checkpoint inhibitors to bolster the host's T-cell mediated clearance of infected cells (Cortese et al., 2019). Because 'JC virus infected cells' represents a pathological state rather than a single molecular target, therapeutic focus is often directed toward specific viral proteins such as the Large T-antigen or the VP1 capsid protein, or toward restoring the host's immune surveillance mechanisms.

Other names

Human polyomavirus 2JC polyomavirusJCPyVJC virus infected cells

Current therapeutic strategies target the virus or the infected state through various mechanisms: inhibition of viral DNA polymerase to halt replication (e.g., Cidofovir), blockade of the 5-HT2A serotonin receptor to prevent viral entry into glial cells (e.g., Mirtazapine), and the use of immune checkpoint inhibitors to reverse T-cell exhaustion and enhance the endogenous immune response against JCV-infected cells (e.g., Pembrolizumab) (Cortese et al., 2019; StatPearls, 2023).