Oncogenic Viruses

Of the DNA tumor viruses the papovaviruses have received particular attention because they are known to cause tumors in a variety of animals. The name papovavirus is derived from the first two letters of the three prototypes: rabit, papilloma virus, polyoma virus and siman vacuolating virus-40 (SV 40).

The capsid of the papilloma-polyoma group consists of 72 morphological units assembled from 420 structure units (T=7). The surface lattice is skewed and the skewing may be right handed or left handed. The virion consists of only DNA and protein. The capid proteins.

Polyoma and SV 40 viruses. Both these viruses are similar in size and general structure. The viral particles are about 45nm in diameter. It contains about 5,000 nucleotide pairs. A single-strand break by cleavage of a phosphodiester bond converts the supercoiled DNA into a relaxed circular form with a sedimentation coefficient of 16S. A double stranded break of the supercoiled form converts it into the linear form with a sedimentation coefficient of 14S.

The polyoma virus is responsible for tumors in mice. The virus can be cultured in permissive mouse cell lines, the cells of which support replication and growth of the virus. The virus undergoes a lytic cycle in which the host cells ultimately die and liberate a large number of virus particles. The virus can also infect rat and hamster cells which are transformed into tumor cells without liberating large amounts of virus particles. Such infection is said to be non-lytic, and the cells are called non-permissive cells.

Proteins. The proteins may be considered under two heads, early proteins and late proteins.
Early Proteins. Early after infection, before the replication of DNA begins, the T antigen (or tumor-antigen) can be detected in the cell nucleus. The synthesis of the T antigen is inhibited by interferon, which specifically inhibits viral proteins synthesis but not cell protein synthesis. This suggests that the T antigen is coded by the virus DNA. More direct evidence for this comes from micro-injection experiments in which SV40 RNA complementary to early viral DNA was injected into epithelial cells in a mouse cell culture.

Late proteins. The capsid proteins are the late proteins. In SV40 only two capsid proteins have been indentified. These are the major capsid proteins VP1 and the minor capsid proteins VP2. VP3 may be present, but the data are not consistent. The polyoma viruses have there capsid proteins VP1, VP2 and VP3.

Replication of DNA. The DNA replication mechanism can be divided into four stages, initiation, elongation, segregation and maturation.
 
1. Intiation of replication occurs at a unique site, called the origin of replication (0), on the DNA molecule in both polyoma and SV40 viruses. In SV40 the origin of replication lies at about 0.67map units on the physical map and in polyoma at about 71units.
 
2. Elongation. Both polyoma and SV40 viruses replicate bidirectionally from the point of origin. The primer nucleotides are then removed and the resulting gaps closed. The enzymes required for this are DNA polymerase and legase.

3. Segregation of progeny DNA. Chain elongation continues until the two replication forks reach the termination region. Each duplex contains a circular parental strand and a linear progency strand. The two ends of the latter are separated by a gap.

4. Maturation. During maturation DNA polymerase and polynucleotide ligase activity is required to close the gap and join the two ends of linear DNA to produce a complete circle. Winding of the DNA strand then takes place, resulting in the supercoiled form. Proteins are probably involved in the winding process. Histones may be attached to the DNA to produce nucleoprotein complexes.