Episomal DNA of a BK virus variant in a human insulinoma

Abstract

BK virus (BKV) DNA was detected by blot hybridization in a human adenoma of pancreatic islets from patient I.R. BKV DNA was free, and no evidence was found of viral sequences integrated into cellular DNA. Virus was rescued by transfection of human embryonic fibroblasts with tumor DNA. The DNA from rescued virus (BKV-IR) was different from wild-type BKV DNA by restriction endonuclease mapping. The genome of BKV-IR is 235 base pairs (bp) shorter than the genome of wild-type BKV. This alteration originates from a deletion of approximately 300 bp involving HindIII fragments B and D, and an insertion of 70 bp in the region of HindIII fragment C. Transformation of hamster kidney cells was induced by total tumor DNA as well as by BKV-IR and BKV-IR DNA. No antibodies to BKV tumor (T) antigen were detected in the patient's serum by immunofluorescence. The significance of episomal BKV DNA in a human tumor is discussed.

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

“…This restriction pattern is similar to that of BKV-IR (Fig. 2), a BKV variant rescued from a human tumour of pancreatic islets (Caputo et al, 1983;Pagnani et al, 1986) and is compatible with an insertion into the regulatory region of the viral genome, which is in HindlII fragment C, as well as with a deletion around map unit 0.54 where a BgllI site and the HindlII site between fragments B and D are located.…”

Oncogenic transformation by BK virus and association with human tumors

“…Small tag cooperates with large Tag in transformation by reducing serum dependence of transformed cells (Bouck et al, 1978;Sleigh et al, 1978;Martin et al, 1979;Frisque et al, 1980). Indeed, a low efficiency of stable transformation and a reduced incidence of tumors with a longer latency period was observed with BKV-IR (Pagnani et al, 1986), a BKV strain bearing a deletion of 253 bp which removes sequences coding for the carboxyl-terminus of small tag (Caputo et al, 1983). Moreover, BKV small tag binds the catalytic (36-kDa) and regulatory (63-kDa) subunits of protein phosphatase 2A (PP2A) (Rundell et al, 1981), inactivating their function.…”

Anticancer activity of an adenoviral vector expressing short hairpin RNA against BK virus T-ag

“…Indeed, a lower efficiency of stable transformation and a reduced tumor incidence associated with a longer latency were described as properties of a naturally occurring BKV variant, BKV-IR, lacking the carboxy-terminus of the t-ag. 12,13 The continuous expression of a functional T-ag, detectable in all BKV-transformed cells, is necessary for the maintenance of transformation. 14 Likewise, studies on the highly homologous SV40 virus have demonstrated that T-ag expression is necessary for the maintenance of transformation [15][16][17][18] and its inhibition by antisense RNA in SV40-positive human mesothelioma cells restores p53 function and induces cell growth arrest and apoptosis.…”