Recombinant Simian Virus 40 Large Antigen [His]

Simian virus 40 (SV40) is a DNA tumor virus capable of infecting and transforming human mesothelial cells in vitro. This class of viruses is usually not oncogenic in natural hosts, but tends to be oncogenic when transmitted across species. SV40 is endemic in rhesus monkeys, and because the original polio vaccine was prepared by culturing poliovirus in tissue-cultured primary rhesus monkey kidney cells, many U.S. polio vaccines were contaminated with SV40 between 1954 and 1963. Experiments in hamster models have shown that subcutaneous injection of SV40 produces sarcomas, intravenous injection of SV40 produces leukemias, lymphomas, and bone tumors, intracardiac injection of SV40 produces mesotheliomas, osteosarcomas, and lymphomas, and intracranial injection produces ventricular meningiomas and other types of brain tumors.

Structurally, SV40 consists of 72 pentamers, of which the major structural protein VP1 encapsulates the 5-kilobase-pair double-stranded DNA genome, and each pentamer contains an internal hydrophobic structural protein, VP2 or VP3. To infect cells, SV40 binds to host cell receptors on the plasma membrane, initiating receptor-mediated endocytosis and directing SV40 to endosomes. The virus is then sorted from endosomes to the endoplasmic reticulum, where it escapes across the endoplasmic reticulum membrane into the cytoplasm. Upon reaching the cytoplasm, the virus is delivered to the nucleus, where its genome is transcribed and replicated, leading to lysogenic infection or cell transformation.

Figure 1. SV40 entry pathway
(Source: Chen YJ, et al. 2019)

The powerful tumor-inducing ability of SV40 is largely related to its major tumor protein, SV40 large tumor antigen (Tag). Tag binds and inactivates multiple cellular tumor suppressors, including pRb and p53, thereby simultaneously impairing two cellular pathways that regulate the G1/S transition and G2/M checkpoints of the cell cycle. SV40 Tag requires TP53 to transform human cells, and the Tag-p53 complex inactivates the oncogenic activity of TP53, on the other hand, binds to and activates the IGF receptor and induces cell growth. This mechanism helps SV40 to circumvent apoptosis in the early stages of infection and support tumor growth.

Recombinant Simian Virus 40 Large Antigen