Neoplastic growth

Infection – the introduction of viral genetic material – results in significant cellular changes designed to promote virus replication. In the majority of the examples we have looked at so far, the CPE ultimately results in cell death. However, as we have seen with HPV, infection with some viruses instead leads to sustained and often increased mitosis. This can contribute to the development of neoplasia (new cell growth), which may lead to oncogenic events. Viruses contribute to cancer formation by two main routes; those DNA viruses that stimulate cell mitosis do so as a result of their own, unique oncogenic proteins, while the oncogenic RNA viruses alter the expression pattern of cellular oncogenes.

Several of the DNA viruses we have mentioned have been implicated as being co-factors in the development of a range of malignancies. All have one or more proteins, essential for their normal replication cycle, which promote the cell cycle. We have described the role of the E6 and E7 proteins in HPV that block tumor suppressor proteins in infected basal cells and a range of transforming proteins (the T-antigens) in Polyomaviruses also activate mitosis in infected cells. The smallest HBV protein, the X-protein, is thought to block the action of p53 (like the HPV E7 protein) but it does so by an unknown mecha- nism, and only a proportion of long-term chronic HBV infections progress to hepatocel- lular carcinoma. The Herpesviridae can also, in some conditions, contribute to cancer formation, the most common member being EBV, which is associated with a number of cancers such as Burkitt’s lymphoma and nasopharyngeal carcinoma.

The RNA viruses that stimulate mitosis and lead to cancerous outcomes are all, with the exception of the hepatitis C virus, members of the family Retroviridae. They have been assigned into three subgroups, according to their mechanism and speed of activity. The fast-acting or transducing retroviruses cause mitosis by expressing an oncogene that they have acquired (into their genome) from a previous infected cell. The gene is expressed in addition to their essential genes and is often mutated as a result of frequent (and uncorrected) genome copying during replication. Infection with such a virus therefore usually leads to high-level expression of an altered oncogenic protein, stimulating mitosis and forming tumors in a short period, perhaps within just a few weeks of infection. The slower cisacting retroviruses induce mitosis by increasing the expression of cellular oncogenes. Integration of the viral (dsDNA) genome into a chromosome allows nearby cellular genes to be influenced by the strong promoters within the virus genome. The result is that infected cells give rise to tumors within a few months of the primary infec- tion. The third group is the trans-acting retroviruses, which also increase the expression of cellular oncogenes. They do so through the action of viral proteins (transcription factors) and cancers can take several years to appear.