Simian virus 40 (SV40) is a monkey virus that was introduced into the human population by contaminated poliovaccines. The vaccines were produced in SV40 infected monkey cells between 1955 and 1963. The site of latent infection in humans is not known but the presence of SV40 in urine suggests the kidney as a possible site of latency. SV40 is a small DNA virus that is studied extensively because it is able to transform and immortalize multiple cell types (Ozer 2000, Saenz-Robles et al. 2001).
Polyoma viruses infect mammals causing tumors and cancer. Similarly to polyoma viruses, SV40 contains a DNA that is associated with histones in a circular complex containing 20- 22 nucleosomes (Varshavsky et al., 1977). SV40 DNA is located in a 50 nm capsid which is composed of homopentameters of the major capsid protein, VP1 (43 kilo Daltons) associated with one of the minor structural proteins VP2 or VP3. Under physiological salt and pH conditions, VP1 alone remains disassociated, and at pH 5, it assembles into tubular structures. Between pH 4 and pH 7, VP2 allows the VP1 pentameters to assemble in spherical particles and incorporates VP1. Furthermore, the virus has an icosahedral symmetry and contains 72 pentameters (Liddington et al., 1991). Figure 1shows the proposed structure of SV40 DNA and the length of each region within the virus. The diagram highlights the arrangement of the early and late regions. Furthermore, it shows the clockwise and counter clockwise symmetry of the large T antigen (TAg), small T antigen (tag), and the major capsid proteins within the virus.
Figure 1: diagram of the SV40 virus genome.
In 1989, Fogleman et al. analyzed the uncoating and penetration of Simian virus (SV 40). It uses the ganglioside GM1 as a receptor and enters host cells by activating the caveolar/lipid raft pathway of endocytosis (Damm et al., 2005). After internalization, the first station is the caveosome, a pH neutral, caveolin containing endocytic organelle distinct for endosomes. From the caveosome, the virus moves in noncaveolar vesicles along microtubules to the endoplasmic reticulum (ER) (Kartenbeck et al., 1989, Pelkmans et al, 2001). After translocation from the ER into the cytosol the virus is thought to enter the nucleus via nuclear pore complexes where transcription and replication take place (Clever et al., 1991).
Usually, the timing of cell division is under strict control, involving a network of signals. Mutations in one or more of these networks can trigger cancer. Mutations are changes in DNA that cause changes in proteins. In cells, any changes in DNA are regulated by repair mechanisms such as p53, a tumor suppressor gene. In cells containing undamaged DNA, the p53 protein is highly unstable and is present at very low concentrations. The unstable state is attributed to its interaction with ubiquitin ligase, Mdm2. The latter transfers multiple ubiquitin molecules onto the p53 protein. As a result, the ubiquitylated p53...