John Cunningham virus antigen (JCV antigen)

John Cunningham virus (JCV) antigens are the protein components of the JC polyomavirus, a ubiquitous human pathogen that remains latent in the kidneys and lymphoid tissues of most healthy individuals. The viral genome encodes early proteins, such as the Large T-antigen and Small T-antigen, which are essential for viral DNA replication and can drive oncogenic transformation, as well as late proteins including the structural capsid proteins VP1, VP2, and VP3 (UniProt P03071, P03089). In the context of severe immunosuppression, such as in HIV/AIDS or during treatment with immunomodulatory drugs like natalizumab, JCV reactivates and undergoes mutations that allow it to infect oligodendrocytes and astrocytes in the central nervous system, leading to Progressive Multifocal Leukoencephalopathy (PML) (StatPearls, PMID: 30209053). Therapeutic targeting of these antigens is a critical area of research, focusing on neutralizing antibodies against VP1 to block viral entry and adoptive T-cell therapies designed to recognize and eliminate JCV-infected cells (PMID: 30134136). Additionally, immune checkpoint inhibitors are being explored to enhance the endogenous T-cell response against these viral antigens in patients with active PML.

Other names

JC polyomavirus antigenJCPyV antigenLarge T-antigenSmall T-antigenVP1 capsid proteinVP2 capsid proteinVP3 capsid proteinAgnoprotein

Neutralization of viral entry by binding to the major capsid protein (VP1); induction of cellular immunity via adoptive T-cell transfer to eliminate JCV-infected cells; checkpoint inhibition to reinvigorate exhausted JCV-specific T-cells.