Link between Viruses and Cancer

What is Cancer?
Cancer is one of the most serious medical problems. A tumour is the growth or lump of tissue resulting from neoplasia, abnormal new cell growth and reproduction due to loss of regulation. Tumour cells have abnormal shapes and altered plasma membranes that contain distinctive tumour antigens. There unregulated proliferation and differentiation result in invasion can result in invasive growth that forms unorganised cell masses. This reversion of primictive or less differentiated state is called anaplasia.

Types of Cancer?
There are two types of tumours known as benign tumour and malignant tumours. Benign is not cancerous, while malignant tumours are cancerous and can cause cancers such as carcinoma. The stages involve local growth of the tumour and damaging the nearby tissues, this can then spread to the lymph channels and nodes and finally they can then spread all over the other areas of the body such as small blood vessels and then get carried in the blood stream to other parts of the body.

The relationship between Viruses and Cancer
There are many causes of cancer, and only few that are related to viruses, 30-60% are related to diet and cigarette smoke. Many chemicals in our surroundings are carcinogenic and may cause cancer by inducing gene mutations or interfering with normal cell differentiation. However it is important to note that not many cancers are linked to environmental factors. 

Viruses are known to cause many animal cancers, but it has been difficult to prove that this is the case with human cancers: the list below show those that can cause cancer:

• EBV (Epstein Barr virus) is one of the best studied human cancer viruses. EBV is a herpes virus and can cause two cancers. Burkitt’s lymphoma is a malignant tumour of the jaw and abdomen found in the children. EBV also caused nasopharyngeal carcinoma. Both EBV particles and genomes are found within tumour cells. Burkitts lymphoma also has high level blood level of antibodies to EBV.
• Hepatitis B virus appears to be associated with one form of liver cancer and can be integrated into human genome. (Heptacellular carcinoma) 
• Hepatitis C causes cirrhosis of the liver, which can lead to liver cancer.         
• Human herpes virus 8 and HIV are associated with Kaposis sarcoma. 
  
• Human papillomaviruses have been linked to cervical cancer. 

Some animal viruses have the potential to change a cell from a normal cell into a tumour cell. This process is called transformation. Viruses known to cause cancer are called oncoviruses. All known human dsDNA oncoviruses trigger cancerous transformation of cells. They encode proteins that bind to and there by inactivate cellular proteins known as tumour suppressors.

Examples of proteins that can lead to cancer?
There are two major HPV proteins E6 and E7:

E6 binds to p53, a major tumor suppressor in the cell that normally activates transcription of p21, an inhibitor of kinases that promote mitosis. 

The E6 oncoproteins in HPV have been shown to be one of the main players in the progression to cervical cancer. E6 in HPVs that are at high risk of causing cancer can complex with p53, which is an important tumor suppressor that plays a role in directing the cellular response to genotoxic and cytotoxic stresses that threaten genomic stability. It functions as a sequence specific transcription activator that is necessary to regulate cell growth as well as tumor growth suppression. The p53 protein suppresses cell growth by transcriptionally activating p21, which inhibits the cell-cycle kinases critical for G1 progression and cell growth.

HPV E6 has also been shown to induce degradation of p53 through ubiquitin-dependent proteolysis. E6 forms a complex with the cellular ubiquitin protein ligase E6-AP, which is then able to bind and ubiquinate p53.

p53 usually acts to arrest G1 growth or to induce apoptosis in the cell to allow the host DNA to be repaired or for the cell to be eliminated if the DNA is irreparable. E6-expressing cells do not manifest a p53-mediated cellular response to DNA damage, which leads to genomic instability. E6 can also activate telomerase independent of p53, leading to immortalization of the infected cell. There is also evidence that E6 can induce abnormal centrosome duplication, leading to genomic instability and aneuploidy.

 E2F is a cell-cycle activator that is regulated by the binding of pRB, a cellular tumor suppressor. HPV protein E7 can bind to pRB, rendering it unable to bind and regulate E2F, which then can freely activate the cell cycle to progress uncontrollably.  

Retro viruses release their oncogenic powers in a different manner. Some carry oncogenes captured from host cells many, many generations ago. Thus they can transform the host cell by bringing the oncogene into the cell. The human retro virus HTLV-1 and HTLV-2 transform a group of immune system cells called T cells by producing regulatory proteins that sometimes activates genes involved in cell division as well as stimulating virus reproduction. The second virus transformation mechanism used by retro virus involves the integration of a viral genome into the host chromosome such that strong, viral regularity elements are near a cellular proto-oncogene. This results in such a high level of expression of cellular protein that the gene is now oncogene.

Keywords!
* Oncogene - is a gene that has the potential to cause cancer. In tumour cells, they are often mutated or expressed at high levels. Many abnormal cells normally undergo a programmed form of death (apoptosis). Activated oncogenes can cause those cells to survive and proliferate instead. Most oncogenes require an additional step, such as mutations in another gene, or environmental factors, such as viral infection.

*Proto-oncogene is a normal gene that can become an oncogene due to mutations or increased expression.          

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