Association of BK virus with human brain tumors and tumors of pancreatic islets

Abstract

BK virus (BKV) DNA was detected by Southern blot hybridization in 19 out of 74 (25.6%) human brain tumors and in 4 out of 9 (44.4%) human tumors of pancreatic islets. BKV DNA was free, in an episomal state and generally in a low copy number (0.2 to 2 genome equivalents per cell). Only occasional tumors contained 10 to 20 genome copies per cell. Viral DNA sequences integrated into cellular DNA were not detected. A number of tumors expressed BKV-specific RNA and T antigen. By transfection of total tumor DNA into human embryonic fibroblasts, viruses with the biological and antigenic properties of BKV were rescued from 6 brain tumors and from 2 tumors of pancreatic islets. Restriction endonuclease mapping of the genomes of the rescued viruses showed that they differ from wild-type BKV. They are all similar to each other and to BKV-IR, a virus previously rescued from a human tumor of pancreatic islets, suggesting the possible association of a BKV variant with specific types of human neoplasms. The significance of the relationship of these BKV variants to human tumors and their possible etiologic role in human oncogenesis are discussed.

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).…”

Lack of association of cytomegalovirus with human brain tumors

“…While DNA from several types of polyoma viruses has been detected in a variable percentage of human brain tumors, [5][6][7][8][9] there has been no conclusive evidence to indicate that such viral agents directly promote tumorigenesis. Simian virus 40, a contaminant of polio vaccines utilized between 1955 and 1963, [8][9][10] in particular has been implicated as a causative agent in the development of neurologic malignancies, as viral sequences have been detected in brain tumors at an overall frequency of approximately 35%.…”

Oncogenic transformation by the human polyomaviruses

“…BKV DNA sequences have been reported in a range of human tumors, many of which do not ®t the normal spectrum of anatomical sites thought to be infected by the virus, including rhabdomyosarcoma, lung, Kaposi's sarcoma, pancreas, liver, brain, and various urinary tract neoplasms (Barbanti-Brodano et al, 1987;Caputo et al, 1983;Corallini et al, 1987;De Mattei et al, 1995;Dorries et al, 1987;Fiori and Di Mayorca, 1976;Flaegstad et al, 1999;Monini et al, 1995aMonini et al, ,b, 1996Negrini et al, 1990;Pater et al, 1980) (for review see Imperiale, 2000). Another study found no evidence for BKV in brain tumors (Arthur et al, 1994).…”