virus and cancer

How do viruses cause cancer? pt 2

'Deliberate' interference with control of the cell cycle 'Accidental' activation of cell genes Retroviral oncogenes Damage to immune defenses

Damage to immune defenses

Interactions between cell proteins and proteins produced by oncogenic viruses can lead to breakdown of immune defenses that may allow the development of a cancer. E.g. Papillomavirus proteins can prevent apoptosis of virus-infected cells----leading to cancer.

Do they actually cause cancer?

-Although many humans are persistently infected by viruses that are potentially oncogenic, only small percentages develop virus-linked cancers. -E.g. ~3% of women persistently infected with one of the high-risk strains of HPV (human Papillomavirus) develop cervical carcinoma. -Suggesting that virus infection alone do not cause cancer. -Other factors: environment, host genetics and immunodeficiency (AIDS patients are much more likely to develop Kaposi's sarcoma).

Papillomavirus-linked cancers

-Keratinocytes (skin cells), the host cells of papillomaviruses, normally stop dividing as they differentiate, -but a papillomavirus needs much of the DNA-replicating machinery of the host cell, -so the virus induces the cell into the S phase. -The cell then undergoes cycles of cell division, but occasionally the division results in chromosomes unchecked and leads to cancer.

How do they cause cancer?

-Most virus-induced cancers develop after a long period of persistent infection with an oncogenic virus. -Some persistent infections are latent for much of the time, with only small numbers of virus genes expressed. -Others, such as HBV infection, are productive. They are able to evolve rapidly, which allows them to keep one step ahead of acquired immune responses.

Stages of tumor development

-Tumor initiation is thought to be the result of a genetic alteration leading to abnormal proliferation of a single cell.

introduction

-oncogenic virus: A virus that is able to cause cancer. -Evidence that a virus is oncogenic: -regular presence of virus DNA in the tumor cells . -virus DNA is integrated into a cell chromosomes. -In many cases one or more of the virus genes are expressed in the tumor cell and virus proteins can be detected. -Viruses cause cancer: ~20% of cancers in female ~8% of cancers in male

Accidental' activation of cell genes

A virus protein might bind to cell proteins (not intended targets) and push a cell towards a cancerous state by activating a cell gene that is switched off, or by enhancing the rate of transcription of a gene that is being expressed at a low level. E.g. Tax protein of HTLV-1 (retrovirus) affects many gene expression.

Prevention of virus-induced cancers

Prevent transmission of the viruses! The main modes of transmission of oncogenic human viruses

Retroviral oncogenes

Some retroviruses have the ability to cause cancer because of the presence in the viral genome of an oncogene. When a proto-oncogene is mutated or aberrantly expressed it becomes an oncogene. E.g. The src gene encodes a protein kinase; overphosphorylation of the enzyme's substrates is a key process in the development of these tumors.

HeLa cells

The oldest and most commonly used human cell line. Derived from cervical cancer cells taken in 1951 from Henrietta Lacks. Part of the genome of HPV-18 is integrated into the genome of HeLa cells. These viral proteins promotes S phase.

Deliberate' interference with control of the cell cycle

several proteins produced by oncogenic viruses can interact with p53, pRb and other proteins that control cell growth and division, increasing the probability of a cell being pushed into repeated cycles of division.