Simian Virus 40 (SV40 T antigen)

Sources/Clones
Biogenesis (0H9, 0G5), Chemicon, Oncogene (PAb416, PAb419, PAb280), Pharmingen (Pab101, Pab122) and Santa Cruz (PAb101, Pab108).

Fixation/Preparation
The use of this antibody was confined to the staining of fixed tissue culture cells (Montano and Lane, 1984) until the recent application of antigen retrieval (Baker-Cairns et al, 1996).

Background
SV40 T antigen (Ab-3) is a mouse monoclonal antibody with specificity for antigenic determinants unique to the SV40 small t antigen and non-reactive with SV40 large T antigen (Montano & Lane, 1984). Both antigens are encoded by the early region of the SV40 genome (Tooze, 1973).
SV40 large T antigen is an 81 kD multifunctional viral phosphoprotein. Some of its functions are essential to the viral replication in monkey cells. Others contribute to its neoplastic transforming activity (Livingston & Bradley, 1987).
The large T antigen binds DNA and complexes with p53 protein (Lane and Crawford, 1979). It also forms a specific complex with the P105 product of the retinoblastoma susceptibility gene (De Caprio et al, 1988).

Applications
The use of this antibody has been confined to the research laboratory to define the cellular location of small t antigen in subcellular extracts of SV40-infected cells (Montano and Lane, 1989). Pab280 reacted strongly with a cytoplasmic form of small t antigen that appears to be associated with the cytoskeleton. Small t was found to accumulate late in the SV40 lytic cycle and was localized in both the cytoplasm and the nucleus of cells infected with wild-type SV40 (Montano and Lane, 1984). Research applications have centered around the use of SV40 as an effective gene transfer vector in vitro (Strayer, 1996), the immortalization of cell lines and the stimulation of developmental abnormalities and tumorigenesis in transgenic mice (Kelly et al, 1991; Rutland et al, 1991; Kivela et al, 1991; Kon et al, 1997; Webber et al, 1997).

Comments
The recent demonstration that 60% of human mesotheliomas contain and express SV40 sequences stimulated a great deal of interest. It has also been shown that SV40 large T antigen interferes with the normal expression of the tumor suppressor gene p53 in human mesotheliomas which raises the possibility that SV40 may contribute to the development of human mesotheliomas (Carbone et al, 1997). SV40 has been demonstrated in fixed tissue with the novel application of a DNA thermal cycler for antigen retrieval (Baker-Cairns et al, 1996).

References
•Baker-Cairns B, Meyers K, Hamilton R et al 1996. Immunohistochemical staining of fixed tissue using antigen retrieval and a thermal cycler. Biotechniques 20: 641-650.

•Carbone M, Rizzo P, Grimley PM et al 1997. Simian virus-40 large-T antigen binds p53 in human mesotheliomas. Nature Medicine 3: 908-912. mesotheliomas. Nature Medicine 3: 908-912.

•De Caprio JA, Ludlow JW, Figge, J et al 1988. SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene. Cell 54: 275-283.

•Kelly KA, Agarwal N, Reeders S, Herrup K 1991. Renal cyst formation and multifocal neoplasia in transgenic mice carrying the simian virus 40 early region.

•Journal of the American Society of Nephrology 2: 84-97.

•Kivela T, Virtanen I, Marcus DM et al 1991. Neuronal and glial properties of a mucrine transgenic retinoblastoma model. American Journal of Pathology 138: 1135-1148.

•Kon Y, Miyoshi I, Maki K et al 1997. Morphological study of pituitary tumorigenesis in transgenic mice induced by hybrid oncogene of the thyrotropin beta-subunit and the simian virus 40 large T-antigen. Histology and Histopathology 12: 981-990.

•Lane DP, Crawford LV 1979. T antigen is bound to a host protein in SV40-transformed cells. Nature 278: 261-263. Livingston DM, Bradley MK 1987. The simian virus 40 large T antigen. A lot packed into a little. Molecular Biology and Medicine 4: 63-80.

•Montano X, Lane DP 1984. Monoclonal antibody to simian virus 40 small t. Journal of Virology 51: 760-767.

•Montano X, Lane DP 1989. Monoclonal antibody analysis of simian virus 40 small t-antigen expression in infected and transformed cells. Journal of Virology 63: 3128-3134.

•Rutland PS, Ollerhead GE, Platt-Higgins AM 1991. Morphogenetic behavior of simian virus 40-transformed human mammary epithelial stem cells on collagen gels. In Vitro Cell Development Biology 27A: 103 112.

•Strayer DS 1996. SV40 as an effective gene transfer vector in vivo. Journal of Biological Chemistry 271: 2741-2746.

•Tooze J 1973. Molecular biology of tumor viruses, Part 2, 2nd edn. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory.

•Webber MM, Bello D, Quander S 1997. Immortalized and tumorigenic adult human prostatic epithelial cell lines: characteristics and applications. Part 2. Tumorigenic cell lines. Prostate 30: 58-64.

Bibliografia
Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.