Viruses And Cancer

Question 1

What are the two ways in which we associate virus with cancer?

Answer 1

1. Epidemiology, line up presence of cancer with presence of virus.
2. If you introduce viral genes into the cell, do they induce oncogenesis

Question 2

What are the 3 mechanisms of oncogenesis?

Answer 2

1. Modulation of cell cycle control
2. Modulation of apoptosis
3. ROS-mediated damage

Question 3

What is the way in each virus can directly cause cancer?

Answer 3

Via oncogenes

Question 4

how can viruses indirectly cause cancer?

Answer 4

Via immunomodulation

Question 5

What does pRB do?

Answer 5

Control of G1/G0 - S phase blockade

Question 6

What does cyclin D1 do?

Answer 6

Regualtion of CDk4/6
Triggered by the PI3K/AKT pathway

Question 7

What does beta-catenin do?

Answer 7

Accumulation during S-phase induces cell proliferation
Prevents apoptosis

Question 8

When are S phase genes repressed?

Answer 8

When Rb and E2F are in complex

Question 9

When are there induction of s phase genes ?

Answer 9

When Rb and E2F are apart

Question 10

What is G1/S phase controlled by in the cell cycle?

Answer 10

Cyclin dependent kinases

Question 11

How is apoptosis triggered extrinsically?

Answer 11

Usually between interactions between Fas ligand and Fas on the plasma membrane

Question 12

How is apoptosis triggered internally?

Answer 12

Through release of MMPs and AIF protein. This induces apoptosis through DNA fragmentation

Question 13

What type of molecule is Bcl2?

Answer 13

A molecule that is pro survival

Question 14

What is the normal extrinsic pathway for apoptosis?

Answer 14

Caspases cause depolarisation of mitochondrial membranes
Lead to release of cytochrome c, activation of caspase 8, then leads to apoptosis

Question 15

What does Bcl2 do to extrinsic apoptosis pathway?

Answer 15

Blocks this pathway, stops release of cytochrome c

Question 16

What does EBV do with Bcl2?

Answer 16

Encodes its own protein

Question 17

How does PI3K/AKT pathway affect cellular growth?

Answer 17

Is triggered or maintained, these are kinases that lead to promotion of cell growth

Question 18

What does NS5A do to AKT/PI3K pathwya?

Answer 18

Blocks the regulator

Question 19

What do v-FLIPs do?

Answer 19

Inhibit apoptosis signalling through death receptors

Question 20

What do free radicals target?

Answer 20

DNA
Protein
RNA
Lipids

Question 21

How do free radicals promote cancer?

Answer 21

1. Mutating cancer related genes
2. Activating signal transduction pathways
3. Promoting angiogenesis
4. Exerting selective pressure (p53 and NO.)

Question 22

What are 4 key examples of virus-associated cancer?

Answer 22

Burkitt’s lymphoma
Nasopharyngeal carcinoma
Cervical cancer
Hepatocellular carcinoma

Question 23

Where is Burkitt’s lymphoma and what populations is it affecting?

Answer 23

Young children, slightly biased to males
Where malaria is endemic

Question 24

What role does malaria have on Burkitt’s lmyphoma?

Answer 24

We all harbour EBV, but malaria has a role in causing illness due to being immunosuppressed

Question 25

What is the difference between endemic Burkitt’s lymphoma and sporadic Burkitt’s lymphoma?

Answer 25

Endemic is with the EBV virus
Sporadic is when you have a chance of getting the cancer without the virus

Question 26

What virus is nasopharyngeal carcinoma associated with?

Answer 26

EBV

Question 27

What is the distribution of nasopharyngeal carcinoma?

Answer 27

North Africa, Hong Kong, southern China etc. is different to association with Burkitt’s lymphoma

Question 28

What is the co factor for nasopharyngeal carcinoma in South china?

Answer 28

Dietary preference for salted fish, this contributes to mutagenic effect

Question 29

What is the cofactor in North Africa?

Answer 29

Have rancid butter int he diet, this is carcinogenic food contribution

Question 30

What are the three proteins to remember for HPV?

Answer 30

E6, E7 and E2

Question 31

What type of proteins are E6 and E7?

Answer 31

Transforming proteins

Question 32

What is E2 and what does it do?

Answer 32

Regulatory protein, controls level of expression of E6 and E7 from long control region

Question 33

What are the two high risk HPV genotypes?

Answer 33

16 and 18

Question 34

What does E6 disregulate in high risk genotypes?

Answer 34

P53, reduction in p53 to low levels, stops expression

Question 35

What can E7 bind directly to?

Answer 35

Retinoblastoma protein

Question 36

What happens to develop hepatocellular carcinoma?

Answer 36

Not just presence of virus but also genetic susceptibilities

Question 37

What viruses cause hepatocellular carcinoma?

Answer 37

HBV and HCV

Question 38

What are the two tumour suppressor genes that are often inactivated in HCC?

Answer 38

P53 and pRB

Question 39

What is the oncogene that is activated in HCC?

Answer 39

Beta-catenin

Question 40

What is the general process for HBV infection and cancer development?

Answer 40

Can have a stochastic (semi random) integration event
It may happen or it may not, so could occur at any time in HBV infection
Viral genome gets into an episome, this replicates, get unchecked cellular replication, ROS production and inactivation of p53

Question 41

What is the difference between HCV and HBV leading to cancer?

Answer 41

HepC has no integration event because it is an RNA virus

Question 42

What is the stage of developing HCC from HCV?

Answer 42

Get infected, triggered viral proteins
Only 1-5% get HCC, doesn’t happen in 2 years, takes 15-20 years

Question 43

How does HCV lead to HCC?

Answer 43

HCV core promotes oncogenesis
Modulates apoptosis
Drives cellular proliferation
Generates ROS