Viruses And Cancer Flashcards
What are the two ways in which we associate virus with cancer?
- Epidemiology, line up presence of cancer with presence of virus.
- If you introduce viral genes into the cell, do they induce oncogenesis
What are the 3 mechanisms of oncogenesis?
- Modulation of cell cycle control
- Modulation of apoptosis
- ROS-mediated damage
What is the way in each virus can directly cause cancer?
Via oncogenes
how can viruses indirectly cause cancer?
Via immunomodulation
What does pRB do?
Control of G1/G0 - S phase blockade
What does cyclin D1 do?
Regualtion of CDk4/6
Triggered by the PI3K/AKT pathway
What does beta-catenin do?
Accumulation during S-phase induces cell proliferation
Prevents apoptosis
When are S phase genes repressed?
When Rb and E2F are in complex
When are there induction of s phase genes ?
When Rb and E2F are apart
What is G1/S phase controlled by in the cell cycle?
Cyclin dependent kinases
How is apoptosis triggered extrinsically?
Usually between interactions between Fas ligand and Fas on the plasma membrane
How is apoptosis triggered internally?
Through release of MMPs and AIF protein. This induces apoptosis through DNA fragmentation
What type of molecule is Bcl2?
A molecule that is pro survival
What is the normal extrinsic pathway for apoptosis?
Caspases cause depolarisation of mitochondrial membranes
Lead to release of cytochrome c, activation of caspase 8, then leads to apoptosis
What does Bcl2 do to extrinsic apoptosis pathway?
Blocks this pathway, stops release of cytochrome c
What does EBV do with Bcl2?
Encodes its own protein
How does PI3K/AKT pathway affect cellular growth?
Is triggered or maintained, these are kinases that lead to promotion of cell growth
What does NS5A do to AKT/PI3K pathwya?
Blocks the regulator
What do v-FLIPs do?
Inhibit apoptosis signalling through death receptors
What do free radicals target?
DNA
Protein
RNA
Lipids
How do free radicals promote cancer?
- Mutating cancer related genes
- Activating signal transduction pathways
- Promoting angiogenesis
- Exerting selective pressure (p53 and NO.)
What are 4 key examples of virus-associated cancer?
Burkitt’s lymphoma
Nasopharyngeal carcinoma
Cervical cancer
Hepatocellular carcinoma
Where is Burkitt’s lymphoma and what populations is it affecting?
Young children, slightly biased to males
Where malaria is endemic
What role does malaria have on Burkitt’s lmyphoma?
We all harbour EBV, but malaria has a role in causing illness due to being immunosuppressed
What is the difference between endemic Burkitt’s lymphoma and sporadic Burkitt’s lymphoma?
Endemic is with the EBV virus
Sporadic is when you have a chance of getting the cancer without the virus
What virus is nasopharyngeal carcinoma associated with?
EBV
What is the distribution of nasopharyngeal carcinoma?
North Africa, Hong Kong, southern China etc. is different to association with Burkitt’s lymphoma
What is the co factor for nasopharyngeal carcinoma in South china?
Dietary preference for salted fish, this contributes to mutagenic effect
What is the cofactor in North Africa?
Have rancid butter int he diet, this is carcinogenic food contribution
What are the three proteins to remember for HPV?
E6, E7 and E2
What type of proteins are E6 and E7?
Transforming proteins
What is E2 and what does it do?
Regulatory protein, controls level of expression of E6 and E7 from long control region
What are the two high risk HPV genotypes?
16 and 18
What does E6 disregulate in high risk genotypes?
P53, reduction in p53 to low levels, stops expression
What can E7 bind directly to?
Retinoblastoma protein
What happens to develop hepatocellular carcinoma?
Not just presence of virus but also genetic susceptibilities
What viruses cause hepatocellular carcinoma?
HBV and HCV
What are the two tumour suppressor genes that are often inactivated in HCC?
P53 and pRB
What is the oncogene that is activated in HCC?
Beta-catenin
What is the general process for HBV infection and cancer development?
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
What is the difference between HCV and HBV leading to cancer?
HepC has no integration event because it is an RNA virus
What is the stage of developing HCC from HCV?
Get infected, triggered viral proteins
Only 1-5% get HCC, doesn’t happen in 2 years, takes 15-20 years
How does HCV lead to HCC?
HCV core promotes oncogenesis
Modulates apoptosis
Drives cellular proliferation
Generates ROS
