Disease relevance of BFPyVgp5

• The most important differences include a large T antigen remarkably reduced in size, and an origin of replication region with fundamental deviations from the origin structure of all other polyomaviruses [1].
• RESULTS: Most animals expressing wild-type large T antigen developed pancreatic insulinomas and lymphomas and died between 3 and 6 months of age [2].
• Interaction of retinoblastoma protein family members with large T-antigen of primate polyomaviruses [3].
• Large T antigen is responsible for both viral and cellular transcriptional regulation, virion assembly, viral DNA replication, and alteration of the cell cycle [4].
• Infection with the Ad5-SVR4 virus was used to introduce the large T antigen encoding region of the SV40 virus into bovine and human corneal endothelial cells [5].

High impact information on BFPyVgp5

• Cells transformed by Polyoma virus (Py) can undergo a high rate of excision or amplification of integrated viral DNA sequences, and these phenomena require the presence of homology (i.e., repeats) within the viral insertion as well as a functional viral large T antigen (T-Ag) [6].
• Phosphorylation is not diminished in extracts of polyoma tsA mutant-infected cells shifted to the nonpermissive temperature late in infection, conditions which inactivate the large T antigen [7].
• By 48 h after infection, almost all (92.8%) bovine corneal endothelial cells expressed large T antigen [5].
• Bovine and human corneal endothelial cells which expressed large T antigen proliferated and the characteristic morphologic features of corneal endothelium were maintained [5].
• In contrast, large T antigen alone is sufficient to induce tumors in the endocrine pancreas and thymus [2].

Chemical compound and disease context of BFPyVgp5

• Polyomavirus large T antigen coprecipitates with p53 phosphorylated on serine 18 and also with p21Cip1/WAF1 [8].

Biological context of BFPyVgp5

• We present evidence that the large T antigen interacts specifically with DNA sequences present in the non-coding region of BFDV; by indirect DNA immunoprecipitation mapping and DNase I footprinting, four regions including 12 DNA-binding sites have been determined that cover most of the BFDV non-coding region [9].
• Our results are compatible with the hypothesis that large T antigen destabilizes the cellular genome, and that specific mutations arising from this process may contribute to cell immortalization [10].
• Simian virus 40 (SV40) and polyomavirus (Py) DNA replication require cellular proteins and a virus-encoded early gene product, large T antigen (SVT and PyT, respectively) [11].
• This recombinant plasmid, pSV01, binds to a purified T antigen in vitro and replicates in monkey cells when supplied with large T antigen [12].
• Activation of IFN-stimulated gene factor 3 was inhibited in cells derived from a tumor induced by wild-type MPyV but not those from a mutant that lacks the pRB binding site of the large T antigen [13].

Anatomical context of BFPyVgp5

• SV40 small t antigen which has previously been considered unable to transform cultured cells by itself, was nevertheless able to transform sup+ BHK lines to anchorage independence in the absence of the viral large T antigen [14].
• Umbilical cord endothelial cells expressing large T antigen: comparison with primary cultures and effect of cell age [15].
• By using micro-positron-emission tomography, interactions between p53 tumor suppressor and the large T antigen of simian virus 40 were visualized in tumor xenografts of HeLa cells stably transfected with the imaging constructs [16].
• Infection of primary human prostate epithelial cells with BK polyomavirus dramatically induced Dnmt1 transcription following large T antigen (TAg) translation and E2F activation [17].
• When grown in 100 microM Zn2+, transformed myocytes expressed the large T antigen, divided rapidly, and acquired an apparently unlimited proliferative capacity [18].

Associations of BFPyVgp5 with chemical compounds

• The viral large T antigen bound to Janus tyrosine kinase 1 and inactivated signaling through IFN receptors [13].
• Large T antigen of SV40 interacts with p53, pRb/p107/p130 family members, and the cyclic AMP-responsive element-binding protein (CREB)-binding protein (CBP)/p300 [19].
• Thus the loss of the growth inhibitory effect of vitamin D3 in HBL100 cells may be caused by the expression of the large T antigen in the cells, and provide further evidence that VDR is required for efficient growth inhibition by vitamin D3 [20].
• Only 2 cases showed strong/diffuse and moderate/focal staining for LTag with both representing invasive high-grade urothelial carcinoma (where no inclusions were seen on hematoxylin and eosin-stained sections) and both demonstrating positive immunostaining for p53 [21].
• Sodium butyrate treatment did, however, result in the appearance of a new nuclear protein which bound specifically to a SV40 promoter fragment containing large-T antigen binding sites I and II [22].

Other interactions of BFPyVgp5

• A recombinant virus containing a genomic copy of the BFDV early region was used for small t antigen expression, and corresponding intron-deleted cDNAs for production of large T antigen derivatives [9].

Analytical, diagnostic and therapeutic context of BFPyVgp5

• Immunocytochemistry revealed that > 95% of the cells express the large T-antigen at both temperatures [23].
• Gene targeting in rat embryo fibroblasts promoted by the polyomavirus large T antigen [24].
• We have established an assay to detect JC viral DNA in brain tissue and CSF of patients with progressive multifocal leukoencephalopathy (PML) and amplified a 106-base pair segment of the gene encoding JC viral large T antigen by polymerase chain reaction (PCR) from the brains of eight patients with PML and from one of six CSF samples [25].
• ALM is, however, unaffected in early gene expression as measured both by indirect immunofluorescence of large T antigen and by transformation levels of rat F-111 cells [26].
• The activity of the 56K protein may be associated with its presence on the cell surface where, either alone or acting together with the large T antigen, it might provide the surface activity responsible for tumor-specific surface and/or transplantation antigen activities [27].

References