Expression of viral T-antigen in pathological tissues from transgenic mice carrying JC-SV40 chimeric DNAs

Abstract

Immunostaining methods were used to detect viral T-antigen and the cellular protein p53 in pathological tissues obtained from transgenic mice carrying JC-SV40 hybrid viral DNAs. A transgenic mouse carrying the SV40 regulatory region and JC virus (JCV) T-antigen-coding sequences exhibited an SV40-characteristic choroid plexus papilloma that expressed JCV T-antigen and p53. JCV-associated pathology was observed in two other mice in which the JCV regulatory signals directed SV40 T-antigen-induced adrenal neuroblastomas and brain neoplastic cells. However, these mice also exhibited an SV40-characteristic osteosarcoma and abdominal lymphoma that contained SV40 T-antigen and p53-positive cells. Contrasting thymic pathology was observed in the two types of mice where the SV40 regulatory region directed a JCV T-antigen-induced thymoma in one mouse, and the JCV regulatory region directed SV40 T-antigen-induced thymic hypoplasia in two other mice.

Progressive Multifocal Leukoencephalopathy: Molecular Biology, Pathogenesis and Clinical Impact

“…and immature oligodendrocytes [113]. SV40 T protein expressing trans genic mice also demonstrated tumors, particularly of the choroid plexus [114], Using hybrid genes containing the SV40 regulatory region and JCV T-Ag coding sequences, SV40-characteristic choroid plexus tumors expressing JCV-specific T-Ag and p53 have been found [115], JCV was also inoculated intracranially into old world monkeys such as rhesus macaques as well as new world monkeys, owl and squirrel monkeys [116. 117], The owl monkeys were highly susceptible to JCV oncogenicity with a 60% incidence of glioblastomas.…”

Animal Models of Human-Papillomavirus-Associated Oncogenesis

“…Such a model could be used to evaluate the role of the HPV protein in the pathogenesis of disease. This approach has been successfully used with the papovaviruses JC and SV40 in transgenic mice [102].…”

Detection of polyomaviruses and herpesviruses in human adrenal tumors

“…They have been involved in the development of several human cancers and lymphomas, but their role in human adrenal tumors has never been investigated, although experimental evidences indicate that polyomaviruses can infect and transform cells of the adrenal cortex and the adrenal medulla (Small et al, 1986;Ressetar et al, 1993Ressetar et al, , 1997Tischler et al, 1993;Servenius et al, 1994;Flaegstad et al, 1999;Thomas et al, 2000;Hornsby et al, 2002). We have recently reported the case of a patient with a large NFA, which showed histological features consistent with HCMV infection, whose presence was confirmed by detection of HCMV DNA and proteins (Pomara et al, 2006).…”

“…Our finding of polyomaviruses in ACC and in malignant pheochromocytoma is intriguing, since these viruses have been associated with adrenal malignancy in experimental animal models, such as transgenic mice containing early regions of polyomaviruses, and in studies of human cancers. In particular, JCV-and SV40-containing mice have been shown to develop highly malignant adrenal neuroblastomas that metastasize to other tissues, whereas BKV-containing mice develop primary hepatocellular carcinomas and renal tumors (Small et al, 1986;Feigenbaum et al, 1992;Ressetar et al, 1993;Servenius et al, 1994). In humans, BKV sequences and large T-antigen expression were demonstrated in 18 out of 18 neuroblastomas, but not in normal adrenal medulla (Flaegstad et al, 1999).…”