Lec 16: Viruses and Cancer

Question 1

Cells in malignant tumors can

Answer 1

invade nearby tissues and spread to other parts of the body.

Question 2

All cancer starts from: (4)

Answer 2

• a single normal cell
• tumorigenesis including mutation
• activation of oncogenes
• inactivation of tumor suppressor genes.

Question 3

Tumor initiation is thought to be the result of

Answer 3

of a genetic alteration leading to abnormal proliferation of a single cell.

Question 4

oncogenic virus =

Answer 4

a virus that is able to cause cancer

Question 5

Evidence that a virus is oncogenic:

Answer 5

1. ) regular presence in the tumour cells of virus DNA.
2. ) virus DNA is integrated into a cell chromosomes.
3. ) In many cases one or more of the virus genes are expressed in the tumour cell and virus proteins can be detected.

Question 6

Viruses cause cancer:

%’s

Answer 6

~20% of cancers in female

~8% of cancers in male

Question 7

How do viruses cause cancer? (3)

Answer 7

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

Question 8

Although many humans are persistently infected by…

Example:

Answer 8

…viruses that are potentially oncogenic, only small percentages develop virus-linked cancers.

(Ex: ~3% of women persistently infected with one of the high-risk strains of HPV (human Papillomavirus) develop cervical carcinoma.)

Question 9

Does virus infection alone cause cancer?

Answer 9

no, other factors: environment, host genetics and immunodeficiency (AIDS patients are much more likely to develop Kaposi’s sarcoma).

Question 10

4 ways viruses cause cancer:

Answer 10

1. ) deliberate interference with control of the cell cycle
2. ) accidental activation of cell genes that promote cell proliferation (binding to cell proteins that aren’t supposed to be activated)
3. ) retroviral oncogenes (ex: RSV –> had oncogenes from previous host cells during replication that accidentally incorporated host oncogene into new host gene)
4. ) immune defense damage

Question 11

(Deliberate interference with control of the cell cycle)

Several proteins produced by oncogenic viruses can…

Answer 11

…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.

Question 12

p53, pRb function:

Answer 12

control cell growth and division

Question 13

action of p53:

Answer 13

damaged DNA –> p53 –> p21 (cell cycle arrest) OR puma/noxa (apoptosis)

Question 14

Papillomavirus-linked cancers: (4)

Answer 14

1. ) Keratinocytes, the host cells of papillomaviruses, normally stop dividing as they differentiate,
2. ) But a papillomavirus needs much of the DNA-replicating machinery of the host cell,
3. ) So the virus induces the cell into the S phase.
4. ) The cell then undergoes cycles of cell division, but occasionally the division results in chromosomes unchecked and leads to cancer. E.g. HPV promotes S phase in HeLa cells.

Question 15

(Accidental activation of cell genes)

A virus protein might bind to…

Answer 15

…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.
(ex: Tax protein of HTLV-1 (retrovirus), which affects many gene expression)

Question 16

(Retroviral oncogenes)

Some retroviruses have the ability to…

When a proto-oncogene is…

Answer 16

… cause cancer because of the presence in the viral genome of an oncogene.

…mutated or aberrantly expressed it becomes an oncogene.
(ex: The src gene encodes a protein kinase; overphosphorylation of the enzyme’s substrates is a key process in the development of these tumors)

Question 17

(Retroviral oncogenes)

A single gene (src, encodes a protein tyrosine kinase) of RSV is found to be…

Answer 17

…responsible for the ability of RSV to induce tumors in birds and transform fibroblasts in culture.

Question 18

(Damage to immune defenses)

Interactions between cell proteins and proteins produced by oncogenic viruses can lead to…

Answer 18

…breakdown of immune defenses that may allow the development of a cancer.
(ex: Papillomavirus proteins can prevent apoptosis of virus-infected cells—-leading to cancer)