Mechanism of oncogenic viruses and Prevention.

How do virus causes cancer.

Most virus-induced cancers develop after a long period of persistant infection with an oncogenic virus. (for T cell leukaemia around 60 years).

Although many humans are persistently infected by the virus that are potentially oncogenic, only small percentages develop virus-linked cancers. So it is clear that virus alone do not cause cancer. Other factors are involved:

  • Complex interplay between the state of the host.
  • Environmental factors to which the host is exposed.
  • Host genetic factors.
  • Cellular changes induced by the virus.
  • Virus proteins synthesized during persistent infections play roles in the conversion of normal to cancer cells. 

 

Mechanisms Involved:

(a) ‘Delibrate’ interference with control of the cell cycle.

Many cells in the animal body grow and divide either slowly or not at all; the latter are arrested in the G1 phase of the cell cycle and are said to be in the G0 state. The control of the cell cycle is mediated by many proteins; two that play key role in humans are p53 and retinoblastoma protein (pRb).

Virus proteins that can interfere with the contol of the cell cycle include the HPV early proteins E6 and E7. Papillomavirus have small genomes about 8kbp and require the cell’s DNA synthesizing functions that are available in the S phase of the cell cycle. E6 and E7 make these functions available by localizing to the nucleus and binding to cell proteins.

E6 binds to p53, promoting its degradation, and E7 binds to pRb-E2F complexes causing their dissociation. E2F is an elongation factor which enhance DNA synthesis. As long as pRb is bound to E2F, no DNA syntheis will occur. The outcomes of this dissociation makes E2F free from pRb-E2F complexe and this transition will make the cell to move into S phase synthesizing viral DNA.

(b) ‘Accidental’ activation of cell genes.

Some virus proteins are able to bind to cell proteins that may not be the intended targets and may trigger events that are of no value to the virus, but may be harmful to host. 

A virus protein might inadvertently 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. 

For example: Tax protein of HTLV-1, it activates the expression of its gene known as tax. this tax may interact with cell genes and some of proto-oncogenes (eg:c-myc) can be activated or their may be a boost in the expression resulting in cancer. 

 

(c) Retroviral Oncogenes 

Some retroviruses have the ability to cause cancer because of the presence in the viral genome of an oncogene. The retroviral genes were drived from cell proto-oncogenes and are closely related to them. 

When a proto-oncogene is mutated or deleted or aberrantly expressed it becomes an oncogene. The oncogene-carrying retroviruses have the ability to induce rapid formation of tumors, usually 1-6 weeks post infection.

Interaction between cell proteins and proteins produced by oncogenic viruses can lead to breakdown of immune defenses that may allow development of cancer,

1st mechanism: RNA by Reverse transcriptase is converted in to DNA which gets integrated into host genome. If Viral DNA gets integrated near proto-oncogene it gets activated and gives hyper expression and result into oncogene and then cancer.

2nd mechanism: It posses a viral oncogenes. Viral DNA which contain V-onc genes get integrated into host genome resulting in cancer. 

 

Prevention of Viral induced Cancer: 

  • prevent transmission of viruses.
  • strategies aimed at reducing the risk of transmission 
  • vaccination
  • Attempted elimination from the body of persistent infections with oncogenic viruses.

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