Chapter 23- Viruses and Cancer

Epstein- Barr virus-linked cancers

Endemic" Burkitt's lymphoma (BL) is a B cell tumor that occurs with a high frequency in children in central Africa and Papua New Guinea. Endemic" Burkitt's lymphoma (BL) is a B cell tumor that occurs with a high frequency in children in central Africa and Papua New Guinea.

Damage to Immune Defenses

Interactions between cell proteins and oncogenic virus proteins can lead to breakdown of immune defenses that may allow the development of a cancer. Virus proteins may interfere with apoptosis, and hence prevent the death of virus-infected cells. Some of the proteins produced by EBV and KSHV in latently infected cells can interfere with acquired immune responses

proteins of viruses considered in this chapter can interact with p53 and/or pRB

V40 large T antigen (binds to p53 and pRB); KSHV latency-associated nuclear antigen (binds to p53 and pRB); HTLV-1 Tax protein (binds to p53)

"Deliberate" interference with control of cell activities

. The control of the cell cycle is mediated by many proteins; two that play key roles in humans are p53 and retinoblastoma protein (pRb). the absence of the protein in some individuals, due to mutations in both copies of the gene, leads to the development of retinoblastoma (cancer of the retina)

Accidental activation of genes

A virus protein might inadvertently push a cell toward a cancerous state by activating a cell gene that is switched off, or by enhancing the transcription of a gene that is normally expressed at a low level. Some retroviruses can induce tumor formation as a consequence of integrating their provirus into a cell chromosome at a site that puts a cell gene under the control of a virus promoter

Overview of cancer induction by viruses

For a number of viruses more than one mechanism might be involved. One such virus is HTLV-1, a complex retrovirus with auxiliary genes. The Tax protein, in conjunction with cell transcription factors, functions as a transcription factor for the virus, stimulating the promoter in the LTR. can inactivate cell cycle regulators including p53. Consequently this protein stimulates the cell cycle, inhibits apoptosis, and can induce chromosome instability

Hepatocellular carcinoma

Hepatocellular carcinoma (liver cancer) accounts for 4-5% of cancer cases in the world. A number of factors are implicated as causative agents, including consumption of mold toxins in food, but most cases are associated with two viruses: hepatitis B virus (HBV) and hepatitis C virus (HCV). Liver cancer is the most common virus-associated cancer in men

HOW DO VIRUSES CAUSE CANCER?

Most virus-induced cancers develop after a long period of persistent infection with an oncogenic virus; for adult T cell leukemia this period is exceptionally long. e virus infections alone do not cause cancer. Other factors are involved and these include exposure to particular environmental factors, host genetic factors, and immunodeficiency.

Polyomavirus linked cancers

Polyomavirus virions have the same characteristics as those of the papillomaviruses, except that they are slightly smaller. most infections are subclinical. Merkel cell carcinoma, a rare skin cancer that mainly affects elderly and immunosuppressed people. suggestions that SV40 is linked with some types of human cancer, including primary brain cancer and malignant mesothelioma, but these suggestions are disputed.

Adult T Cell Leukemia

Regions of the world with a high prevalence of the virus, such as southwest Japan, have a high prevalence of this cancer. HTLV-1 is a retrovirus and the tumor cells each have a copy of the proviral DNA integrated into a chromosome

CELL LINES DERIVED FROM VIRUS-ASSOCIATED CANCERS

The most famous of these, the HeLa cell line, was established from a cervical cancer in the mid-twentieth century and is now used in laboratories around the world. Each HeLa cell contains a copy of part of the genome of HPV-18

Retroviral Oncogenes

When a proto-oncogene is mutated or aberrantly expressed it becomes an oncogene. The src gene, which has been implicated in the development of many cancers, encodes a protein kinase; over-phosphorylation of the enzyme's substrates is a key process in the development of these tumors

There is evidence that high-risk HPVs (especially HPV-16)

are also causative agents of some carcinomas at other body sites, including the vulva, vagina, penis, anus, mouth, head, and neck. Again the evidence is the presence in the tumor cells of HPV DNA

Papillomavirus linked cancers

cervical cancer is third most common form.

Virus proteins that can interfere with control of the cell cycle include the HPV

early proteins E6 and E7, which localize to the nucleus and bind to cell proteins. E6 binds to p53, promoting its degradation, and E7 binds to pRb-E2F complexes, causing their dissociation (E2F is a cell transcription factor that activates DNA synthesis). The outcome of these interactions is the transition of the cell to the S phase.

Virus associated cancers in animals

filterable agents cause a leukosis (a B cell leu kemia/lymphoma) and a sarcoma in chickens. These agents were subsequently shown to be retroviruses; the sarcoma-causing virus was named Rous sarcoma virus. leukemia in cats and cattle, and a retrovirus known as Jaagsiekte sheep retrovirus was found to be responsible for adenocarcinoma of the lung in sheep.

individuals who are persistently infected with HBV or HCV

liver cirrhosis develops. This results in a high rate of cell division to replace the damaged hepatocytes, during which a mutation might occur in one of the cells, and this might eventually lead to cancer

Cancer in a human/animal

malignant tumor, involves continuous clone of cells, transmutation changes result in mutation, activation of oncogenes, and inactivation of tumor suppressors.

Presence in the tumor cells of virus DNA

may be all or part of virus genome, integrated into the cell chromosomes, covalently closed circular DNA

Prevention of Virus-induced cancers

prevent transmission of viruses, Vaccination. Vaccines for HBV and HPV 16 and 18, lower cervical cancer.

Kaposi's sarcoma

rare skin cancer that affected elderly men in the Mediterranean region. Since the arrival of AIDS that picture has changed. It is one of the most common cancers in people with AIDS; in these patients the cancer is more aggressive and it disseminates throughout the body. There is also good evidence linking KSHV with two other human cancers: primary effusion lymphoma and multicentric Castleman's disease.

Papilloma viruses

small DNA viruses of mammals. Enter body through small abrasions in skin and mucous membranes. Hands or genitals and result in warts or carcinoma. HPV-16 is high risk, low risk HPV 6 or 11

A number of other cancers have been found to have associations with EBV, including

some cases of Hodgkin's lymphoma; non-Hodgkin's lymphoma in AIDS; post-transplant lymphoproliferative disorder. The last two cancers develop in patients who are immunocompromised as a result of AIDS or immunosuppressive treatment, respectively

Oncogenic virus-

virus able to cause cancer.