The link between VLA-4 and JC virus reactivation.

Natalizumab represents an effective biological therapy to treat relapsing-remitting forms of multiple sclerosis and Crohn's disease by blocking the migration of inflammatory cells to the brain and gut. Natalizumab, however, is associated with a risk of progressive multifocal leukoencephalopathy (PML) caused by the reactivation of JC virus. The emergence of PML in this setting has moved PML from being a rare disease mostly seen in HIV-infected individuals to become an important cause of complications in patients receiving immunomodulatory treatments. The incidence of PML associated with natalizumab treatment is approximately 1.5:750, but this increases to approximately 1:100 in patients after 24-36 doses based on available estimates of individuals who have a prior history of immunosuppressive treatment and are antibody positive to JC virus. Natalizumab treatment has raised questions about the pathogenesis of PML but also has provided the opportunity to investigate sites of virus latency and mechanisms of trafficking to the brain.