This project investigates cellular tropism of the human polyomavirus, JC virus (JCV), and the role that latently infected cells may play in JCV-induced disease and tumorigenesis. Following childhood infection, JCV remains latent in the body. In immunocompromised individuals, reactivated JCV productively infects oligodendrocytes and astrocytes causing the fatal CNS demyelinating disease, progressive multifocal leukoencephalopathy (PML). While all sites of JCV latency have not been determined, apparent reactivation of JCV occurs in the kidney of women during pregnancy and in organ transplant recipients. When injected intracerebrally into newborn hamsters, JCV establishes a nonproductive infection inducing subsequent brain tumor formation. In the past year we have completed two main studies utilizing the hamster model of JCV infection: 1) Two double-label immunostaining methods identified JCV T-antigen in lectin-labeled blood vessels as well as Factor VIII-labeled brain endothelial cells 7 to 30 days after intracerebral injection of JCV into newborn hamsters. The number of JCV-infected endothelial cells was increased in cyclophosphamide-suppressed hamsters and this increase was most pronounced in the cerebellum in sites of subsequent tumor formation. 2) Polymerase chain reaction (PCR) methods were employed to detect JCV DNA in body organ samples from 6 month-old hamsters inoculated intracerebrally with JCV as newborns. High levels of JCV DNA were found in the brain, kidney and bladder of all hamsters. While variable amounts of JCV DNA were found in the adrenal, pancreas and spleen, JCV DNA was not detected in liver, testis, ovary and uterine samples. These results suggest that in the hamster, JCV persists in a tissue-specific manner 6 months after inoculation. A continuing study has utilized immunostaining and PCR methods to detect the presence of JC or BK polyomaviruses or SV40 monkey polyomavirus in human pediatric medulloblastomas and choroid plexus papillomas. Due to equivocal findings, further investigation is currently being performed.
