Chapter 6 viroids and prions

Chapter 6Virus and cancer

Prepared by: Miss Putri Shareen Binti Rosman

• 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.

Cancer

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.

• Oncogenic DNA Viruses– Adenoviridae– Herpesviridae– Poxviridae– Papovaviridae– Hepadnaviridae

Oncogenic Viruses

Oncogenic RNA Oncogenic RNA virusesviruses RetroviridaeRetroviridae Viral RNA is Viral RNA is

transcribed to DNA transcribed to DNA which can integrate which can integrate into host DNAinto host DNAHTLV 1HTLV 1HTLV 2HTLV 2

Oncogenic viruses

Brief background on cell cycle factors Rb and E2F example

Oncogenic viruses

Example: DNA damage during G1P53 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

Enquist et al., Principles of Virology, ASM, 2004

• 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.

Inactivation of p53 by papillomavirus proteins

HPVn

Enquist et al., Principles of Virology, ASM, 2004

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Chapter 6Chapter 6Novel acellular Novel acellular

infectious agentinfectious agent

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PrionsPrions•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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Figure 13.22

How a Protein Can Be Infectious

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Prion DiseasesPrion Diseases•Prions form Prions form insoluble insoluble deposits in the braindeposits in the brain•Causes neurons to Causes neurons to rapidly degeneration.rapidly degeneration.•Mad cow diseaseMad cow disease (bovine spongiform (bovine spongiform encephalitis: BSE) is encephalitis: BSE) is an examplean example•People in New People in New Guinea used to suffer Guinea used to suffer from from kurukuru, which they , which they got from eating the got from eating the brains of their brains of their enemiesenemies

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• 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

Prions

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ViroidsViroids

•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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Treatment for Viral Treatment for Viral DiseaseDisease

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VaccinesVaccines

• 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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Other Viral TreatmentsOther 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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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)