L06: Viruses And Cancer Flashcards
What are the characteristic features of a virus
DNA/RNA
Protein capsid
Membrane envelope
Why does viruses require a host cell
For translation of viral MRNA
Genome transcription
Genome replication
Give 3 examples of virus that are associated with cancer
Adenovirus
Herpes virus
Papillomovirus
In a tumour cell what happens to oncogenes and tumour suppressor genes
Oncogene is activated
Tumour suppressor gene is inacitved
What is the normal role of tumour suppressor genes
Inhibit cell division
What is the role of proto-oncogenes
Drive cell division and cell cycle
Which viruses in the IARC classification are considered to be carcinogenic
Epstein Barr virus Kaposi sarcoma associated virus Hepatitis C Hepatitis B Humans T cell lymphotrophic virus type 1 High risk human papilloma virus types Merkel cell polyomavirus HIV-1
Which bacteria in the IARC classification is considered to be carcinogenic
Helicobacter pylori
In what type of countries are infectious agents that cause cancer higher in
Developing countries due to better hygiene and better screening programs
What are the 2 ways viruses can behave as carcinogens
Direct
Indirect
What is a direct carcinogen
Viral oncogenes when expressed drive cell cycle and proliferation
What are indirect carcinogens
Viruses that cause cancer through chronic infection, inflammation and immunosuppression that lead to carcinogenic mutation in host
Is HIV-1 a direct or indirect carcinogen
Indirect carcinogen
In HIV what does persistent immune activation lead to in tissues
Chronic tissue damage
When there is cytokine release in HIV what happens to the micro-environment
Changes
What are the other roles of HIV
Increase angiogenesis
Accelerate fibrosis
How is fibrosis accelerated in HIV
By stimulation of extracellular matrix
If there is fibrosis what cancer is likely to occur
Liver cancer
In people with HIV what risk are they are
Increased proliferation of co-existing viruses
What co-existing viruses can occur in HIV patients
EBV
KSHV
Herpes
HBV/HCV
What is the Koch’s postulate useful for
Identifying an infectious as the cause of a specific disease
List the reasons why the Koch’s postulate fails in viral cancer
- Viral infection have a long latency period between primary and tumour development
- only small percent of individuals with the virus develop cancer
- cancer is not only due to the virus because there are other factors involved
- cancer only contains a part of the viral genome (not the whole)
- virus is only one part of the chain
Name a viral infection that shows latency
Herpes (EBV)
What cancer is herpes virus (EBV) associated with
Nasopharyngeal carcinoma
Burkkit lymphoma
Apart from the herpes virus what other factors contribute to burkitt lymphoma
Malaria
Chromosome translocation of c-myc (oncogene) to IG enhancer
Apart from herpes virus what others factors contribute to nasopharyngeal carcinoma
Salted fish
Why does salted fish contribute to nasopharyngeal carcinoma
Salted fish contains nitrosamines that leads to genetic cell changes
What cancer is HPV type 16 and 18 (human papillomovirus) associated with
Cervical cancer
What is HPV 6 and 11 associated with
Anogenital warts
Is HPV classed as a direct or indirect carcinogen
Direct carcinogen
What type of cells does HPV affect
Epithelial cells
What are the 2 viral oncogenes that HPV encodes
E6 and E7 viral oncogene
Which cancer is HPV most associated with
Cervical cancer
What is HPV dependent on for replication of viral DNA
Host cell i.e epithelial cells
Where are epithelial cells mitotically active
In the basal layer
As epithelial cells begins to migrate up from the basal layer what happens to there mitotic activity
Declines
Where does viral DNA amplification of HPV occur
In the mid layers
Where does capsid assembly of HPV occur
In the upper layers
What does viral dna amplification and capsid assembly occur in the upper layers
These layers have poor immune system so it prevents the immune activation that can get rid of the virus
If the HPV is affecting the mid layers what type of cells are these in terms of mitosis
Mitotically inactive with no replication machinery
What happens to the cells in the mid layers to have replication of the virus from occurring
Get pushed back to increase cell division
What are the viral oncogenes of HPV
E6 and E7
What does E7 inhibit
Rb
What is RB
A tumour suppressor gene that prevents inappropriate cell cycle
If RB is not functioning due to E7 bound to RB what tumour suppressor is induced
P53
What does p53 lead to
Apoptosis
What viral oncogene inhibits P53 to stop apoptosis
E6
In a normal cell if there are positive growth signals what happens to RB to proceed the checkpoint
1) positive growth signals activate cyclin D/ CDK4,6
2) cyclin D/cdk4,6 phosphorylates Rb
3) RB results in release of E2F which activates genes to proceed into s phase
What type of signals stop rb from functioning.
Negative growth signal
Stress signal
Describe what happens when there is negative growth signal and stress signal to stop the cell cycle
1) negative growth signal causes the release of P16
2) stress signal causes the release of P53
3) p53 activates p21
4) p16 and p21 inhibit cyclin D, CDK4,6 so E2F remains inhibited and cell cycle stops
Therefore when E7 binds to RB what happens
E2F is released which promotes transcription of genes to proceed into the s phase
What other host cell factor does E6 bind to P53 with
E6AP
When E6 and E6AP binds to P53 what happens to P53
Degrades
With the use of E7 and E6 what happens to the virus
Survives
In combination with the virus, genetics, diet what happens
Tumour
How to we prevent hepatitis b from occurring
Hepatitis b vaccine
What happened to liver cancers when there hep b vaccine was introduced
Liver cancer decreased
How do we control cervical cancer due to HPV
Cervical screening programmes
What does cervical screening involve
Cervical smear test
What does the cervical smear test look for
Cytological abnormalities
Apart from cervical smear test what other test is involved in cervical screening
HPV dna testing
Why is HPV dna testing involved
Because some women can be missed with screening
What are the other methods of controlling HPV
Prophylactic HPV vaccine
What are 2 HPV vaccines used in the U.K.
Cervarix
Gardasil
How does these HPV vaccine work
Stimulate the production of neutralising antibodies so it can bind to a real virus upon exposure
At what age are people injected with HPV vaccine
Young age before they are sexually active