IV. VIRUSES
F. ANIMAL VIRUS LIFE CYCLES
5. The Role of Viruses in Tumor Production
Fundamental Statements for this Learning Object:
1. Viruses are responsible for over 12% of the world’s cancers.
2. 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).
3. The Epstein-Barr virus (EBV), the Kaposi sarcoma-associated herpesvirus (KSHV), the human immunodeficiency virus (HIV), and human T-lymphotropic virus type I (HTLV-I) also increase the risk of certain cancers.
4. The development of tumors is a multistep process depending on the accumulation of mutations altering a number of genes.
5. 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.
Viruses are infectious agents with both living and nonliving characteristics.
1. Living characteristics of viruses
a. They reproduce at a fantastic rate, but only in living host cells.
b. They can mutate.
2. Nonliving characteristics of viruses
a. They are acellular, that is, they contain no cytoplasm or cellular organelles.
b. They carry out no metabolism on their own and must replicate using the host cell's metabolic machinery. In other words, viruses don't grow and divide. Instead, new viral components are synthesized and assembled within the infected host cell.
c. The vast majority of viruses possess either DNA or RNA but not both.
The Role of Viruses in Tumor Production
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, viruses are thought to contribute to over 12% 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 (def) hepatitis in those infected. There is a strong link between chronic infection with HBV and hepatocellular carcinoma (def), 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 Kaposi sarcoma-associated herpesvirus (KSHV) is a herpesvirus transmitted from person to person primarily through saliva, but can also be transmitted sexually, primarily among men who have sex with men. In addition, it can be spread via blood and transmitted from an infected mother to a child. Healthy individuals infected with the virus show no signs or symptoms. KSHV has been linked to several cancers, including Kaposi sarcoma and two rare lymphomas.
The human immunodeficiency virus (HIV), an immunosuppressive virus responsible for AIDS, is spread through unprotected sexual activity, infected drug needles, during pregnancy from mother to child, and through infected breast milk. It is thought that a weakened immune system increases a person’s risk of getting several cancers caused by other viruses, including non-Hodgkin and Hodgkin lymphomas, anogenital cancers, Kaposi sarcoma, possibly oral cancers, and liver cancer. It also increases the risk of other types of cancers, including eye cancer, non-melanoma skin cancer, and possibly lung cancer.
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 (def) and counterbalanced by growth-restricting tumor suppressor genes (def). Mutations that increase the activities of proto-oncogenes to create oncogenes (def) 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.
Medscape article on infections associated with organisms mentioned in this Learning Object. Registration to access this website is free.
Last updated: Feb., 2020
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Gary Kaiser