Epidemiological evidence and molecular basis of interactions between HIV and JC virus

The epidemiology of PML suggests that dysfunction of cellular immune response is the single most important determining factor that predisposes to the development of PML, although gender, genetic factors, and viral strains may also play a role. PML seems to occur disproportionately in the HIV-infected population in contrast to other populations with underlying immunosuppressive conditions. Despite this strong association of HIV and PML, very few experimental studies have addressed this interaction. Nonetheless, these experimental studies suggest that the pathophysiology of PML in HIV-infected patients may be intimately related to products released from HIV-infected cells. Thus, in the absence of specific anti-JCV therapy, any approach aimed at controlling HIV replication would potentially be useful in these patients. Future experimental approaches may include therapeutic vaccines using HIV gene products. In this regard, the HIV Tat protein may be an excellent candidate because it is an early gene product, and immune responses targeted against this protein could potentially not only prevent its interaction with JCV but may also cause cytolysis of HIV-infected cells before viral replication occurs in these cells. Certainly, Tat vaccine seems to be well tolerated in preliminary human studies.