Chapter 30 - Oncogenic Viruses

Summary

INTRODUCTION

Viruses are infectious agents that invade living cells in order to reproduce themselves. Typically they attach to receptors on the surface of the target cell, and once inside the cell they harness the host's protein synthesis and energy-generating pathways to form progeny particles. As a consequence of this type of replicative cycle viruses cause a variety of pathological consequences, which include malignant transformation of host cells. The concept that viruses cause cancer dates back to the first decade of the twentieth century, when experiments by Francis Peyton Rous showed that an agent that passed through a filter could induce tumours in chickens. This pioneering work was recognised more than 50 years later with the 1966 Nobel Prize.

Viruses may alter cells in ways that predispose to cancer through a variety of mechanisms. These include direct mechanisms such as integration of viral DNA into target cells and indirect effects such as inducing an immunodeficient state. The major classes of viruses that are linked to cancer and will be discussed below are retroviruses, herpesviruses, papillomaviruses, hepadnaviruses (hepatitis B), and flaviviruses (hepatitis C).

RETROVIRUSES

Retroviruses comprise a large family of enveloped viruses. A common characteristic of the replication of these viruses is that the mechanism involves reverse transcription of virion RNA into double-stranded DNA. The size of the RNA genome ranges from 7 to 12 kb and there are typically two copies of the RNA genome in each virion particle. DNA formed from RNA reverse transcription is typically integrated into the host genome as a provirus. An outline of the retrovirus life cycle is summarised in Figure 1.

HIV-1, classic example of a retrovirus

The immunodeficiency of HIV-1 infection is associated with an increased incidence of several different malignancies. Included among these are Kaposi's sarcomas, non- Hodgkin's lymphoma, Hodgkin's disease, squamous cell neoplasms and leiomyo - sarcoma in children. Interestingly, this spectrum of malignancies is not common to all immunodeficient states. Kaposi's sarcoma is uniquely increased in HIV-1-infected individuals and also within subgroups of the HIV- 1-infected population.