High Incidence of Ependymomas Induced by BK Virus, a Human Papovavirus: Brief Communication2

Abstract

Ependymomas were produced in 44 of 50 Syrian golden hamsters and in 9 of 31 outbred Swiss mice inoculated intracerebrally with high-titer, purified BK virus (BKV). Tumors contained a T-antigen that reacted with BKV-specific T-antibody in immunofluorescence and complement-fixation tests. A proportion of tumor-bearing animals had antibodies to BKV T-antigen in their sera. BKV could be rescued from two tumor cell lines by Sendal virus-mediated fusion with Vero cells. A low, or lack of, oncogenic activity was displayed by BKV inoculated sc, ip, or iv.

Oncogenic transformation by BK virus and association with human tumors

“…However, both in immunocompetent and in immunosuppressed hamsters, ependymomas, tumors of pancreatic islets and osteosarcomas were the most frequent histotypes, suggesting that BKV may have a marked tropism for specific organs. Tumors induced by BKV in mice and rats were fibrosarcoma, liposarcoma, ostesarcoma, nephroblastoma, glioma and choroid plexus papilloma, the latter arising only in mice (Corallini et al, 1977;Noss et al, 1981;Noss and Stauch, 1984). Moreover, transgenic mice expressing BKV Tag developed hepatocellular carcinoma, renal tumors and lymphoproliferative disease (Small et al, 1986;Dalrymple and Beemon, 1990).…”

“…These tumors contained full-length BKV genomes, but also rearranged and defective BKV DNA molecules. Since BKV shows a specific oncogenic tropism for the ependymal tissue, endocrine pancreas and bones in rodents (Corallini et al, 1977Uchida et al, 1979;Chenciner et al, 1980), BKV DNA sequences were searched by Southern blotting in those rare types of human tumors most frequently induced by BKV in experimental animals such as ependymomas and other brain tumors, insulinomas and osteosarcomas. BKV DNA was detected in a free, episomal state and generally at a low copy number (from 0.2 to 1 genome equivalent per cell) in 19 out of 74 (26%) human brain tumors and in four out of nine (44%) human tumors of pancreatic islets (Corallini et al, 1987b).…”

Characterization of BK virus variants rescued from human tumours and tumour cell lines

“…Tumours induced in experimental animals include brain tumours, tumours of pancreatic islets, osteosarcomas and fibrosarcomas (Corallini et al, 1977Costa et al, 1976;Uchida et al, 1976Uchida et al, , 1979. In agreement with the indications of this experimental pathogenicity, BKV DNA was detected by Southern blot hybridization in human brain tumours and tumours of pancreatic islets (Corallini et al, 1987;D6rries et al, 1987).…”

Integrated and free viral DNA in hamster tumors induced by BK virus.

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(8)(9)(10)(11)(12). When injected intracerebrally, this virus induced tumors in 88% of inoculated hamsters and 29% of inoculated mice, and all tumors were intraventricular ependymomas (11).

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“…The two other most frequent types of tumors induced in hamsters inoculated intravenously with BKV were pancreatic insulinomas (12%) and osteosarcomas (10%). BKV large tumor antigen was detected in BKVinduced tumors (11,12), indicating that at least a portion of the viral genome was being expressed in tumor cells. (Worthington) and again with proteinase K, reextracted with phenol/chloroform, and dialyzed (to be described in detail elsewhere).…”