VIRUSES AND CANCER

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Tumor cells also can arise by non-genetic means through the actions of specific tumor viruses. Tumor viruses are of two distinct types. There are viruses with DNA genomes and those with RNA genomes.

      The viruses that have been strongly associated with human cancers are listed in Table 1. They include human papillomaviruses, Epstein-Barr virus, human herpesvirus 8, hepatitis B virus, hepatitis C virus, and two human retroviruses plus several candidate human cancer viruses. Many viruses can cause tumors in animals, either as a consequence of natural infection or after experimental inoculation.

Table 1. Association of viruses with human cancer

Virus Family	Virus	Human cancer
DNA viruses
Papillomaviridae	Human papillomaviruses	Genital tumors Squamous cell carcinoma Oropharyngeal carcinoma
Herpesviridae	Epstein-Barr virus	Nasopharyngeal carcinoma Burkitt's lymphoma Hodgkin's disease B cell lymphoma
	Human herpesvirus 8	Kaposi's sarcoma
Hepadnaviridae	Hepatitis B virus	Hepatocellular carcinoma
RNA viruses
Retroviridae	human T-cell lymphoma virus	T cell leukemia
Flaviviridae	Hepatitis C virus	Hepatocellular carcinoma

The mode of virally-induced tumors can be divided into two, acutely-transforming or slowly-transforming. In acutely-transforming viruses, the viral particles carry a gene that encodes for an overactive oncogene called viral-oncogene (v-onc), and the infected cell is transformed as soon as v-onc is expressed. In contrast, in slowly-transforming viruses, the virus genome is inserted, especially as viral genome insertion is obligatory part of retroviruses, near a proto-oncogene in the host genome. The viral promoter or other transcription regulation elements, in turn, cause over-expression of that proto-oncogene, which, in turn, induces uncontrolled cellular proliferation. Because viral genome insertion is not specific to proto-oncogenes and the chance of insertion near that proto-oncogene is low, slowly-transforming viruses have very long tumor latency compared to acutely-transforming virus, which already carries the viral-oncogene.

It is thought that when the virus infects a cell, it inserts a part of its own DNA near the cell growth genes, causing cell division. The group of changed cells that is formed from the first cell dividing all have the same viral DNA near the cell growth genes. The group of changed cells is now special because one of the normal controls on growth has been lost.

Depending on their location, cells can be damaged through radiation from sunshine, chemicals from cigarette smoke, and inflammation from bacterial infection or other viruses. Each cell has a chance of damage, a step on a path toward cancer. Cells often die if they are damaged, through failure of a vital process or the immune system; however, sometimes damage will knock out a single cancer gene. In an old person, there are thousands, tens of thousands or hundreds of thousands of knocked-out cells. The chance that any one would form a cancer is very low.

When the damage occurs in any area of changed cells, something different occurs. Each of the cells has the potential for growth. The changed cells will divide quicker when the area is damaged by physical, chemical, or viral agents. A vicious circle has been set up: Damaging the area will cause the changed cells to divide, causing a greater likelihood that they will suffer knock-outs.

Unlike retroviral v-oncogenes, the DNA viruses carry their own genes, which are capable inducing cancer. If the integrated viral genetic material has oncogenic property; it will transform cells into tumor cell lines.  Majority of the DNA viral genes act against p53 genes, thus they release cells from tumor suppressor activity. 

Cellular transformation by DNA tumor viruses, in most cases, has been shown to be the result of protein-protein interaction. Proteins encoded by the DNA tumor viruses, termed tumor antigens or T antigens, can interact with cellular proteins. This interaction effectively sequesters the cellular proteins away from their normal functional locations within the cell. The predominant types of proteins that are sequestered by viral T antigens have been shown to be of the tumor suppressor type. It is the loss of their normal suppressor functions that results in cellular transformation.

This model of carcinogenesis is popular because it explains why cancers grow. It would be expected that cells that are damaged through radiation would die or at least be worse off because they have fewer genes working; viruses increase the number of genes working.

One concern is that we may end up with thousands of vaccines to prevent every virus that can change our cells. Viruses can have different effects on different parts of the body. It may be possible to prevent a number of different cancers by immunizing against one viral agent. It is likely that HPV, for instance, has a role in cancers of the mucous membranes of the mouth.

Considering the whole range of viruses known in animals as well as man, only a small number of agents within particular virus families have direct growth-transforming capacity. What are these viruses and how do they work?