1. Chapter 6 Virus and cancer
Prepared by:
Miss Putri Shareen Binti Rosman

2. Cancer
Activated oncogenes transform normal cells into cancerous cells.
Transformed cells have increased growth, loss of contact inhibition, tumor specific transplant and T antigens.
The genetic material of oncogenic viruses becomes integrated into the host cell's DNA.

3. Oncogenic viruses
that produce tumors in their natural hosts or in experimental animals . induce malignant transformation of cells on culture.
Transformation
changes that accompany the conversion of a normal cell into malignant cell.

4. Oncogenic Viruses Oncogenic RNA viruses Oncogenic DNA Viruses
Retroviridae
Viral RNA is transcribed to DNA which can integrate into host DNA
HTLV 1
HTLV 2
Oncogenic DNA Viruses
Adenoviridae
Herpesviridae
Poxviridae
Papovaviridae
Hepadnaviridae

5. Oncogenic viruses Rapidly dividing cells are linked to cancer.
More easily effected due to their ability for rapid division.
Hodgkins disease and Burkitt’s lymphoma
Associated with viral infections.
1st retroviruse
Discovered in chickens, which induces sarcomas.
Being intensively studied now.
DNA copy is inserted into the host chromosome
If inserted next to a gene which has a long term fx.
The virus acts as a promoter causing uncontrolled cell growth.
Cellular oncogens
Genes that cause uncontrolled growth that were discovered in tumors associated with viral infection.

6. Brief background on cell cycle factors Rb and E2F example
Oncogenic viruses
Brief background on cell cycle factors
Rb and E2F example
Enquist et al., Principles of Virology, ASM, 2004
Example: DNA damage during G1
P53 recognizes DNA damage and activates P21 (p53 recognizes certain types of DNA mismatches)
P21 binds and inactivates the cyclin-CDK complex which has already begun to be produced in response to different signals
DNA repaired, p53 decreases, P21 no longer blocks cyclin-CDK, cell cycle progression

7. Coming out of G1 phase and entering S.
E2F: important transcriptional activator
Enters the nucleus and binds upstream of important nucleotides.
Bound to retinoblastoma protein
Keeps the E2F from entering the nucleus and acting as an important activator.
Cdk2/cyclin A
Phosphorylates Rb causing the release of e2f.
Allows the cell to enter S phase.
DNA damage
Any double stranded DNA breaks causes the dna polymerase to fall off terminating trascritipion.
P53
P53 act as a checkpoint controller to stop cell-cycle progression
If DNA is damaged this protein activates p21 preventing the cell from entering S phase.
P21- blocks the cyclin dependent reaction.
Central player in the decision to commit to S phase.

8. Inactivation of p53 by papillomavirus proteins
HPVn
Viruses have the ability to bind to p53 and controlling it.
Allows the formation of tumors/cancers.
Hpv
Binds to p53 and causing it to be destroyed.
No p53 no cell cycle control.
E1b
Binds to p53 preventing the activation of p21. Lt
Renders p53 unavailable by sequestering from the cell.
Many different ways of effecting p53 and its ability to control the cell cycle.
This can lead to carcinomas, but not 100% of the time.
Enquist et al., Principles of Virology, ASM, 2004

9. Chapter 6 Novel acellular infectious agent
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Prions
Prions are “infectious proteins”
They are normal body proteins that get converted into an alternate configuration by contact with other prion proteins
They have no DNA or RNA
The main protein involved in human and mammalian prion diseases is called “PrP”
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11. How a Protein Can Be Infectious
Figure 13.22

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Prion Diseases
Prions form insoluble deposits in the brain
Causes neurons to rapidly degeneration.
Mad cow disease (bovine spongiform encephalitis: BSE) is an example
People in New Guinea used to suffer from kuru, which they got from eating the brains of their enemies
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13. Prions
Inherited and transmissible by ingestion, transplant, & surgical instruments
Spongiform encephalopathies: Sheep scrapie, Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome, fatal familial insomnia, mad cow disease

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Viroids
Small, circular RNA molecules without a protein coat.RNA does not code any protein.
Infect plants
Resemble introns cut out of eukaryotic
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15. Treatment for Viral Disease
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Vaccines
An attenuated virus is a weakened, less vigorous virus
“Attenuate" refers to procedures that weaken an agent of disease (heating)
A vaccine against a viral disease can be made from an attenuated, less virulent strain of the virus
Attenuated virus is capable of stimulating an immune response and creating immunity, but not causing illness
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17. Other Viral Treatments
Interferon are naturally occurring proteins made by cells to fight viruses
Genetic altering of viruses (attenuated viruses)
Antiviral drugs (AZT)
Protease inhibitors – prevent capsid formation
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18. Antiviral Treatment Strategies
Inhibitors of viral replication
every step in viral replication is potentially a target
targeting host cell functions is generally not feasible (toxicity)