Molecular and biological properties of BK virus-IR, a BK virus variant isolated from a human tumor

Abstract

We describe the molecular and biological properties of BK virus (BKV)-IR, a new BKV variant isolated from a human tumor of pancreatic islets. BKV-IR bears a 253-base-pair (bp) deletion and an 80-bp insertion in the early region of the genome. The deletion abolishes the expression of small-t antigen. The inserted sequences, grouped in four clusters, produce rearrangements in the first and second enhancer elements. They are bound by 12-bp direct repeats and could form a 217-base stem-loop structure suggestive of an insertion sequence. As compared with wild-type BKV, BKV-IR transformed hamster cells with a reduced efficiency and induced ependymomas in hamsters at a lower frequency and with a longer latency period. Tumors induced by BKV-IR, however, showed features of higher malignancy. The possible role of the insertion sequence-like element in transformation by BKV-IR is discussed.

Functional role of BK virus tumor antigens in transformation

“…BKV can induce a variety of tumors in newborn hamsters (47) and in transgenic mice (39). Several variants of this virus have been isolated from a variety of tumors (30). BKV can also efficiently transform human embryonic kidney (HEK) and brain cells in culture (31,35,42).…”

Co‐operation in cell transformation between BK virus and the human C‐harvey‐ras oncogene

“…These findings may be relevant to the role of BKV in human neoplasia, where co-operation or synergism between BKV and cellular oncogenes could occur through the involvememt of BKV variants associated with human tumors (Caputo et al, 1983;Pagnani et al, 1986;Corallini et al, 1987b). These variants contain, in the early region, a putative transposable element enclosing in its sequence 2 viral enhancer repeats (Pagnani et al, 1986).…”

“…These findings may be relevant to the role of BKV in human neoplasia, where co-operation or synergism between BKV and cellular oncogenes could occur through the involvememt of BKV variants associated with human tumors (Caputo et al, 1983;Pagnani et al, 1986;Corallini et al, 1987b). These variants contain, in the early region, a putative transposable element enclosing in its sequence 2 viral enhancer repeats (Pagnani et al, 1986). Several cellular oncogenes are involved in different steps of human carcinogenesis (Bishop, 1983(Bishop, , 1987Slamon et al, 1984) and could be deregulated or activated through a mutagenic effect or enhancement of transcription (Varmus, 1984) by insertion of this transposable sequence.…”

“…BKV DNA, RNA and T antigen have been detected in human brain tumors and tumors of pancreatic aslets (Corallini et al, 1987b). The genome organization of BKV rescued from positive human tumors (Pagnani et al, 1986;Corallini et al, 19876) suggested a possible interaction of BKV DNA sequences with cellular oncogenes. Therefore, we established an experimental model to evaluate a possible co-operation in tumorigenicity between BKV and cellular oncogenes.…”

Detection of specific IgA antibodies against BK virus by ELISA

“…Primary BKV infections have, however, been associated with respiratory symptoms [Goudsmit et al, 19821. Hemorrhagic cystitis in bone marrow transplant recipients and ureteric stenosis in renal allografts recipients have been ascribed to viral activity [Arthur and Shah, 19891. The transforming capacity of BKV [reviewed by Yoshiike and Takemoto, 19861 and the recent findings of viral DNA, RNA, and tumor antigen in human cancer tissue [Pagnani et al, 1986;Corallini et al, 1987;Dorries et al, 19871 point to a possible role for BKV in cancer etiology. This tissue is, however, far from settled.…”