John Cunningham virus: an overview on biology and disease of the etiological agent of the progressive multifocal leukoencephalopathy

John Cunningham virus (JCV), the etiological agent of progressive multifocal leukoencephalopathy (PML), is the first human polyomavirus described. After asymptomatic primary infection which occurs in childhood, the virus spreads by the hematogenous route from the primary site of infection to secondary sites including kidneys, lymphoid tissues, peripheral blood leukocytes, and brain to establish latent infection. During immunosuppression the virus undergoes molecular rearrangements that allow it to replicate in glial tissues causing PML. PML occurs in people with underlying immunodeficiency or in individuals being treated with potent immunomodulatory therapies. Although the hypothesis that immune deficiency is a predisposing factor for PML, there are many unsolved issues including the pathogenic mechanisms related to the interaction of JCV infection/reactivation with the host. This is due to the difficulty of propagating the virus in human cell cultures and the absence of an animal model. This review updates current understanding in the context of JCV and human disease.