INTRODUCTION

In their seminal report in 1958, Astrom, Mancall, and Richardson described a progressive neurological syndrome with characteristic neuropathological findings of demyelination, giant astrocytes, and oligodendrocytes with abnormal nuclei. They named the disorder progressive multifocal leukoencephalopathy (PML). The viral etiology of this neurological disease was not determined until later. PML remained a vanishingly rare disorder seen almost exclusively in individuals with underlying immunosuppressive disorders until the advent of the acquired immunodeficiency syndrome (AIDS) pandemic. In developed countries, PML occurs in approximately 1 in 20 of all human immunodeficiency virus (HIV)-infected persons and AIDS is now the predisposing disorder for 90% of all PML cases. More recently, monoclonal antibodies that result in a highly specific alteration of immune function, such as natalizumab, an α-4 integrin inhibitor, and rituximab, a chimeric monoclonal antibody directed against CD20 receptors on B cells, and whose therapeutic applications have become increasingly prevalent, have been associated with PML.

JC VIRUS AND THE PATHOGENESIS OF PML

In 1965, Zu Rhein and Chou identified viral particles in glial nuclei resembling papovavirus. Subsequently, Padgett isolated polyoma virus from PML brain in glial cell cultures. This virus proved to be a double-stranded DNA virus of icosahedral symmetry. It has a simple DNA genome of 5.1 kilobases in a double-stranded, supercoiled form, encapsidated in an icosahedral protein structure measuring 40 nm in diameter. JC virus (JCV) DNA encodes for three capsid (VP1, VP2, and VP3) proteins and three regulatory proteins (agnoprotein, t, and T).