Progressive multifocal leukoencephalopathy: clinical and molecular aspects.

The fatal CNS demyelinating disease, progressive multifocal leukoencephalopathy (PML), is rare and appears to occur almost always as a consequence of immune dysfunction. Thus, it is associated with HIV/AIDS and also as a side effect of certain immunomodulatory monoclonal antibody therapies. In contrast to the rarity of PML, the etiological agent of the disease, the polyomavirus JC (JCV), is widespread in populations worldwide. In the 40 years since JCV was first isolated, much has been learned about the virus and the disease from laboratory and clinical observations. However, there are many aspects of the viral life cycle and of the pathogenesis of the disease that remain unclear, and our understanding is constantly evolving. In this review, we will discuss our current understanding of the clinical features of PML and molecular characteristics of JCV and of how they relate to each other. Clinical observations can inform molecular studies of the virus, and likewise, molecular findings concerning the life cycle of the virus can guide the development of novel therapeutic strategies.