SV40 large T antigen (Simian Vacuolating Virus 40 TAg) is a hexamer protein that is a dominant-acting oncoprotein derived from the polyomavirus SV40.

The transforming activity of TAg is due in large part to its perturbation of the retinoblastoma (pRb)[1] and p53 tumor suppressor proteins.

[2] In addition, TAg binds to several other cellular factors, including the transcriptional co-activators p300 and CBP, which may contribute to its transformation function.

SV40 was isolated by Sweet and Maurice Hilleman in 1960 in primary monkey kidney cell cultures being used to grow Sabin OPV.

Therefore, in addition to increasing transcription, another function of T-antigen is to alter the cellular environment to permit virus genome replication.

[8][9] A diagnostic pattern for a high-affinity pRb-binding domain was refined using an artificial intelligence pattern-induction program running on a massively parallel supercomputer (Connection Machine-2).

[9] The pRb-binding motif and negatively charged region match to a segment of SV40 TAg beginning at residue 102 and ending at residue 115 as shown below: Functional studies of TAg proteins bearing mutations within this segment (amino acid positions 106 to 114, inclusive) demonstrate that certain deleterious mutations abolish malignant transforming activity.

[1] A detailed computerized bioinformatics analysis,[9] as well as an x-ray crystallography study,[11] have demonstrated the biophysical basis for the interaction between this region of TAg and pRb.

[12] Of note, the highest-risk oncogenic human papillomavirus (HPV) strains (16, 18, 31, 45) encode E7 proteins featuring high-affinity pRb-binding domains which match the diagnostic pattern given above.