7.3.6E: The Role of Viruses in Tumor Production
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- Ying Liu
- City College of San Francisco
Describe how certain viruses may contribute to the development of tumors by altering proto-oncogenes or tumor-suppressor genes.
Name 3 viruses that have been implicated in human cancers.
Some viruses can also play a role in converting normal host cells into tumor cells. These viruses are capable of viral transformation, that is, they transform normal cells into malignant cells. In fact, five viruses, hepatitis B virus (HBV), hepatitis C virus (HCV), human papilloma virus (HPV), Epstein-Barr virus (EBV), and human T-lymphotropic virus type I (HTLV-I) are thought to contribute to over 15% of the world's cancers. Up to 80% of these human viral-associated cancers are cervical cancer (associated with HPV) and liver cancer (associated with HBV and HCV).
The hepatitis B virus (HBV) is a DNA virus that may potentially cause chronic hepatitis in those infected. There is a strong link between chronic infection with HBV and hepatocellular carcinoma, which typically appears after 30-50 years of chronic liver damage and liver cell replacement. Chronic carriers of HBV have a 300 times greater risk of eventually developing liver cancer. Around 90% of individuals infected at birth and 10% of individuals infected as adults become chronic carriers of HBV. There are about one million chronic carriers of HBV in the US. Worldwide, HBV is responsible for 60% of all liver cancer cases.
The hepatitis C virus (HCV) is a RNA virus that may also cause chronic hepatitis in those infected. As with HBV, there is a strong link between chronic infection with HCV and liver cancer, typically appearing after 30-50 years of chronic liver damage and liver cell replacement. Around 85% of individuals infected with HCV become chronic carriers and there are approximately four million chronic carriers of HCV in the US. Worldwide, HCV is responsible for 22 % of all liver cancer cases.
The human papilloma viruses (HPV) are responsible for warts. While warts are generally considered as benign tumors, some sexually-transmitted strains of HPV (HPV-16 and 18 are definitely carcinogenic in humans; HPV-31 and 33 are probably carcinogenic), have been implicated in cervical and vulvar cancer, rectal cancer, and squamous cell carcinoma of the penis. In these tumor cells the viral DNA is usually found integrated in host cell chromosomes. In the US, HPVs are associated with 82% of the deaths due to cervical cancer each year, as well as a million precancerous lesions.
The Epstein-Barr virus (EBV), a herpes virus, normally causes benign proliferations such as infectious mononucleosis and hairy leukoplakia of the tongue. However, it can contribute to non-Hodgkin's lymphoma in AIDS patients and post-transplantation lymphoproliferative diseases, appears to be an essential factor for posterior nasopharyngeal cancer in some individuals, can be a co-factor for Burkitt's lymphoma, and contributes to smooth-muscle tumors in immunosuppressed children.
The retrovirus human T-lymphotropic virus type I (HTLV-I) can induce a rare adult T-lymphocyte leukemia-lymphoma.
The development of tumors is a multistep process depending on the accumulation of mutations altering a number of genes. The altered genes then function collectively to cause malignant growth.
Proliferation of normal cells is regulated by growth-promoting proto-oncogenes and counterbalanced by growth-restricting tumor suppressor genes. Mutations that increase the activities of proto-oncogenes to create oncogenes and/or decrease the activities of tumor suppressor genes can lead to growth of tumors. It is now known that many tumors require both activation of oncogenes from proto-oncogenes and inactivation of tumor suppressor genes for their development.
Viruses are thought to play a role in cancer development both indirectly and directly. Indirectly, the viruses may induce immunosuppression so that cancer cells are not removed by immune responses, as in the case of HIV/AIDS, or they may cause long term damage to tissues resulting in large scale cell regeneration which increases the chances of natural mutation in proto-oncogenes and tumor suppressor genes, as in the case of HBV and HCV. Directly, by integrating into the host cell's chromosomes, some viruses may alter the normal function of the proto-oncogenes and tumor suppressor genes, as is seen with HPV and HBV.
However, most virus-associated cancers have long latency periods of several decades and only a small percentage of the people infected with the virus actually develop the cancer. This indicates other factors promoting changes in cellular genes are also involved. For example, in the case of cervical cancer and HPV, two variants of a tumor suppressor gene known as p53 are known. One form of the p53 gene produces a suppressor protein that is much more susceptible to degradation by an oncoprotein called E6 which is produced by carcinogenic strains of HPV.
Name the three most common viruses associated with cancer in the US and state the cancers with which they are associated.
Summary
- Viruses are responsible for about 15% of the world’s cancers.
- Up to 80% of these human viral-associated cancers are cervical cancer (associated with human papilloma virus or HPV) and liver cancer (associated with the hepatitis B virus or HBV and the hepatitis C virus or HCV).
- The Epstein-Barr virus (EBV) and human T-lymphotropic virus type I (HTLV-I) also increase the risk of certain cancers.
- The development of tumors is a multistep process depending on the accumulation of mutations altering a number of genes.
- Most virus-associated cancers have long latency periods of several decades and only a small percentage of the people infected with the virus actually develop the cancer. This indicates other factors promoting changes in cellular genes are also involved.
Questions
Study the material in this section and then write out the answers to these questions. Do not just click on the answers and write them out. This will not test your understanding of this tutorial.
- Describe how certain viruses may contribute to the development of tumors by altering proto-oncogenes or tumor-suppressor genes. (ans)
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Name 3 viruses that have been implicated in human cancers.
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- People with chronic hepatitis B have a much higher risk of developing liver cancer. This cancer, however, usually appears after decades of chronic infection. Explain the link between HBV and liver cancer and why, if it does develop, it usually takes so long. (ans)
- Multiple Choice (ans)