Polyomavirus JC and Human Cancer: Possible Role of Stem Cells in Pathogenesis

Abstract

The human neurotropic polyomavirus JC virus (JCV) is a small DNA tumor virus and the established etiological agent of the demyelinating disease, progressive multifocal leukoencephalopathy (PML). JCV is widely distributed among the human population, as greater than 80% of adults exhibit JCV-specific antibodies. After initial infection early in life, the virus establishes a persistent nonpathogenic infection in the normal host. In patients with disruptions in the immune system, the virus can undergo reactivation and subsequently cause lytic destruction of oligodendrocytes resulting in PML. In a cellular context that is nonpermissive for viral replication, JCV can contribute to oncogenic transformation. Accordingly, evidence suggests that JCV can induce a variety of tumor types in experimental animals and has been associated with neural and nonneural types of malignancies in humans. Although JCV is considered a neurotropic virus due to its association with PML, it is well-established that the virus persists in the kidney, tonsils, and lymphoid tissues and has been detected in the bone marrow and peripheral blood cells. It is presumed that the blood stream can serve as a conduit to propagate the virus into different organs, including the brain. Given the transforming ability and ubiquitous nature of JCV, it is possible that JCV plays a critical role in the induction of human cancer. However, it remains unknown whether JCV has a causal role in human cancer. In this chapter, we discuss the tumorigenic potential of JCV with special emphasis on the potential role of bone marrow-derived stem cells in the pathogenesis of JCV-associated diseases.