Major capsid protein VP1 (Human polyomavirus 2) (JCV VP1)

Human polyomavirus 2 major capsid protein VP1, also known as JC virus VP1, is the primary structural component of the JC polyomavirus (JCPyV) capsid. It organizes into 72 pentamers to form an icosahedral shell that encapsulates the viral genome and mediates host cell recognition by binding to alpha-2,6-linked sialic acid receptors and the serotonin receptor 5-HT2A. In patients with progressive multifocal leukoencephalopathy (PML), the virus often undergoes specific mutations in the surface-exposed loops of VP1, which can alter receptor tropism and facilitate the infection of glial cells while evading the host's immune response. Therapeutic strategies targeting VP1 include the development of broadly neutralizing human monoclonal antibodies, such as BIIB069, which are designed to block viral attachment and prevent the spread of the virus within the central nervous system. Additionally, research into the VP1 pentameric pore has identified it as a potential target for small-molecule and peptide inhibitors that disrupt viral assembly or DNA packaging. Because JCPyV is a common latent infection in the general population, monitoring VP1-specific antibody levels and genetic mutations is a standard practice for assessing PML risk in immunocompromised patients or those receiving immunomodulatory therapies.

Other names

JCV VP1Major capsid protein VP1JC virus major capsid proteinHuman polyomavirus 2 VP1JCPyV VP1 protein

Neutralization of viral particles and inhibition of viral entry by blocking the interaction between the VP1 surface loops and host cell receptors (sialic acid and 5-HT2A); disruption of capsid assembly or viral DNA packaging through binding to the VP1 pentameric pore or inter-pentamer interfaces.