Induction of Brain Tumors by a Newly Isolated JC Virus (Tokyo-1 Strain)

A newly isolated virus from a patient with progressive multifocal leukoencephalopathy (PML) (Tokyo-1 strain) was found serologically identical to JC virus (Mad-1 strain) and showed high neurooncogenicity in hamsters. Twenty-one animals inoculated intracerebrally with the virus developed brain tumors during a period that averaged 5 months. The tumors were cerebellar medulloblastoma (n = 20); plexus tumor (n = 2) occurred in 1 animal as a single tumor and in another in combination with a medulloblastoma. Thalamic gliomatosis was also present in 6 animals with medulloblastoma. Five mock-infected animals did not develop tumors. Medulloblastoma cells were shown to contain papovavirus T-antigen. In 20 animals examined the medulloblastoma showed a close resemblance to the human medulloblastoma in its histologic, immunocytochemical, and ultrastructural features. Examination of the incipient tumors indicated that the hamster medulloblastoma originated in cells in the neonatal external granular layer. Following infection the cells apparently migrated into the internal granular layer, carrying integrated virus genes and expressing phenotypical transformation. These findings confirm previous reports on the oncogenicity of virus isolates from PML (ZuRhein and Varakis, 1979), but are novel in that with this new isolate tumors could be induced with comparatively low levels of virus inocula.