16. Viruses and Cancer 1

Question 1

What factors can impact the cell and lead to cancer?

Answer 1

1. UV
2. Radiation
3. spontaneous mutations
4. other carcinogens

Question 2

What happens to most cells with mutations?

Answer 2

1. They are repaired
2. The cell is sent into apoptosis

Question 3

Viruses and cancer

Answer 3

1. Viruses are infectious agents that can lead to cancer.
2. Tumour viruses can alter the cells and they then accumulate secondary genetic changes that can then become cancer.
3. BUT this does lead to a potential route that we can vaccinate against these cancers.

Question 4

Cancer and Oncogenic viruses

Answer 4

1. Cancer can be an infectious disease and you can catch it from someone else.
2. 20% of all cancers are virus-associated with their first mutation being due to a virus.
3. Can be DNA or RNA genomes.
4. If a virus is going to cause cancer it needs to be a chronic infection and be in the body for a long time to cause mutations.
5. They are widespread viruses but only cause cancer in the minority of cases.
6. Immunity suggest vaccination of possibilities

Question 5

What proportion of liver cancer is caused by Hepatitis B and C?

Answer 5

75%

Question 6

What cancers do viruses causes?

Answer 6

Cancers of the tissues that they infect and replicate in.

Question 7

What are the 7 oncogenic viruses?

Answer 7

Direct cancer induction:
1. Epstein-Barr virus
2. HPV
3. Human T-cell leukaemia virus
4. Kaposi sarcoma herpesvirus
5. Merkel cell polyomavirus
Cancer induction through chronic inflammation:
6. Hepatitis B
7. Hepatitis C

Question 8

What virus causes liver cancer?

Answer 8

Hepatitis B and C

Question 9

What virus causes cervial cancer?

Answer 9

HPV

Question 10

What virus causes lymphoma and nasopharynx carcinoma?

Answer 10

Epstein-Barr virus

Question 11

What virus causes adult T-cell lymphoma?

Answer 11

Human T-cell lymphotropic virus type 1

Question 12

What virus causes Merkel cell carcinoma?

Answer 12

Merkel cell polyomavirus

Question 13

What virus causes Kaposi sarcoma of the skin, mouth or gut?

Answer 13

Kaposi sarcoma virus

Question 14

How does hepatitis B and C cause cancer?

Answer 14

1. They cause chronic inflammation that causes cell damage and cancer
2. They have some genes that contribute to the carcinogenesis

Question 15

What 4 things are need to prove the association of virus with the cancer?

Answer 15

1. Epidemiological links using population studies and observing cancer in virus patients.
2. The virus and its products are found in the tumour cells.
3. The virus induces tumours in animal models and then infer it also causes cancer in humans.
4. Vaccination with viral production can prevent the tumour by reducing infection.

Question 16

How were animal viruses used in oncogene discovery?

Answer 16

1. Many oncogenes come from viruses and are inserted into the genome.
2. Normally retroviruses have only 3 genes for replication but they can have an extra gene.
3. These regions are inserted and being expressed and cause cancer.

Question 17

What is src?

Answer 17

1. An oncogene
2. named for Rous sarcoma
3. discovered in chickens and then found in humans
4. It is a dominant mutation
5. A tyrosine kinase that activates signalling.

Question 18

What oncogene did Rous Sarcoma virus insert?

Answer 18

Src

Question 19

What oncogene did Myelocytomatosis insert?

Answer 19

Myc

Question 20

What oncogene did Avian erythroblastosis insert?

Answer 20

ErbB - the EGF receptor

Question 21

What is the main way oncoviruses trigger cancer?

Answer 21

Through loss of growth regulation

Question 22

What can viral loss of growth regulation cause?

Answer 22

1. Changes in cell shape.
2. Increased growth rate leading to increased mutation rate.
3. Reduce dependence on attachment signals.
4. Production of growth factors so they can self perpetuate.

Question 23

What does the Ras oncogene do?

Answer 23

Lots of growth and cause the cell to pile on top of each other and lose contact inhibition

Question 24

What oncogene did Harvey and Kirsten rat sarcoma virus insert?

Answer 24

Ras - H-Ras and K-Ras

Question 25

What oncogene did Simian Sarcoma virus insert?

Answer 25

Sis

Question 26

How can Anchorage-independent growth aid cancer cells?

Answer 26

1. The cells don’t need a solid surface or integral attachment to be able to survive
2. They have independent growth and can proliferate with ECM adhesions

Question 27

What hallmarks of cancer do oncoviruses influence?

Answer 27

1. Resisting cell death.
2. Sustain proliferative signalling.
3. Evading growth suppressors .

Question 28

How does Epstein-Barr virus cause sustained proliferative signalling?

Answer 28

1. Its latent membrane protein 1 (LMP1) mimics CD40 to stimulate B cell proliferation.
2. When CD40L binds CD40 it binds the tyrosine kinase JAK3 which recruits proteins.
3. These trigger 3 signalling pathways and production of 3 signalling factors: STAT, JNK and NF-kB.
4. The LMP1 cytoplasmic tail is very similar to CD40 so it leads to the activation of the same proliferative signalling pathways without external binding.

Question 29

What is JNK?

Answer 29

Jun N-terminal kinase

Question 30

How does Epstein-Barr virus mimic BCR signalling?

Answer 30

1. Its latent membrane protein 2a (LMP2a) can mimic the BCR due to the similar cytoplasmic tail.
2. Normally a BCR is activated and triggers proliferation to respond to infection.
3. Tyrosine kinases Lyn, Btk, Syk phosphorylate proteins which leads to survival signals and proliferation.
4. LMP2a causes the same signalling without the antigen binding so absence of infection.

Question 31

How does HPV cause sustained proliferative signalling?

Answer 31

1. Normally growth factors bind Platelet-derived growth factor receptor and epidermal growth receptor.
2. This causes dimerisation and phosphorylation that triggers proliferative signalling.
3. HPV E5 protein is a transmembrane protein that causes the dimerisation instead of the growth factor.
4. E5 acts from within the plasma membrane causing dimerisation, cell signalling and growth.

Question 32

What oncoviral proteins interact with growth suppressors?

Answer 32

1. HTLV1’s Tax binds p53 and Rb
2. HPV’s E6 binds p53 and E7 binds Rb
3. KSHV’s LANA binds p53 and v-CYC and LANA binds Rb

Question 33

What are growth suppressors?

Answer 33

molecules that prevent the cell dividing

Question 34

How does HPV E7 prevent Rb’s function?

Answer 34

1. E7 binds RB
2. It pulls Rb off E2F
3. This means the cell cycle can continue independent of cyclin function
4. similar action to the phosphorylation of Rb by cyclin D

Question 35

How does HPV E6 suppress p53?

Answer 35

1. p53 is a transcription factor produced to inhibit cell growth.
2. E6 binds p53 and prevents it from activating genes even when there is DNA damage.
3. It can also mark p53 for degradation.

Question 36

How does HPV resist cell death?

Answer 36

1. If E6 binds p53 it cannot produce the death inducers it normally does.
2. this prevents the accumulation of death inducers.
3. The cell survives and proliferates even when there is DNA damage

Question 37

How does EBV LMP1 resist cell death?

Answer 37

1. It can induce proliferation and promote survival even when death inducers are present.
2. NF-kB and JNK blocks the transcription of apoptotic factors
3. promotes cell survival