3.3.1: Oncogenic Viruses

Viruses can cause cancer by transforming a normal cell into a malignant cell.

Learning Objectives

• Illustrate how cancer viruses turn normal cells into tumor cells

Key Points

• A direct oncogenic viral mechanism involves either the insertion of additional viral oncogenic genes into the host cell, or the enhancement of already existing oncogenic genes in the genome.
• Tumor viruses come in a variety of forms. Viruses with a DNA genome, such as adenovirus, and viruses with an RNA genome, like the Hepatitis C virus (HCV), can cause cancers. Retroviruses having both DNA and RNA genomes (Human T-lymphotropic virus and hepatitis B virus) can also cause cancers.
• Viruses can become carcinogenic when they integrate into the host cell genome as part of a biological accident, such as polyomaviruses and papillomaviruses.

Key Terms

• oncogenic: Tending to cause the formation of tumors.

Worldwide, cancer viruses are estimated to cause 15-20% of all cancers in humans. Most viral infections, however, do not lead to tumor formation; several factors influence the progression from viral infection to cancer development. These factors include host’s genetic makeup, mutation occurrence, exposure to cancer causing agents, and immune impairment.

Cancer cells have characteristics that differ from normal cells, such as acquiring the ability to grow uncontrollably. This can result from having control of their own growth signals, losing sensitivity to anti-growth signals, and losing the ability to undergo apoptosis, or programmed cell death.  The human genome contains a variety of genes which normally control the growth and replication of cells.  It is important for cells to replicate only when needed (such as to replace dead cells) and that those cells which replicate have a correctly copied genome with no mutations.  One set of genes in human cells, called proto-oncogenes, produces proteins which respond to environmental and intercellular signals and determine whether or not a cell should replicate.  When a proto-oncogene is mutated (into what is now called an oncogene) it can tell the cell to replicate even when it shouldn't.  This results in uncontrolled cell growth.  The other important part of this growth control is to only allow cells with no errors in their genome to replicate.  This is the job of proteins called tumor suppressors.  One of the most critical tumor suppressors is a protein called p53.  Normally, tumor suppressors will force a cell to apoptosis (programmed cell death) if the DNA of the cell is damaged.  In cancer, however, tumor suppressors are disabled (either by the gene being damaged or the protein being inactivated), thus allowing mutated cells to replicate.  The development of cancer usually involves both oncogenes and the disabling of tumor suppressors (Fig. 3.2.1.1).

Oncogenesis (the start of cancer) can occur when a virus infects and genetically alters a cell. Scientists have been able to discern some commonality among viruses that cause tumors. The tumor viruses (or oncoviruses) change cells by integrating their genetic material with the host cell’s DNA. Unlike the integration seen in prophages, this is a permanent insertion; the genetic material is never removed.  The inserted viral DNA could either affect the functioning of a proto-oncogene (resulting in an oncogene and uncontrolled cell growth) or disable a tumor suppressor (resulting in the growth of cells with damaged DNA). In some cases the virus itself carries genes which can impair the proper control of cell growth.

Figure 3.2.1.1: Mutations Leading to Increased Cell Division: Cancer is caused by a series of mutations. Viral infections contribute to the process through genetic alteration.

The insertion mechanism can differ depending on whether the nucleic acid in the virus is DNA or RNA. In DNA viruses, the genetic material can be directly inserted into the host’s DNA. RNA viruses must first transcribe RNA to DNA and then insert the genetic material into the host cell’s DNA.