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.
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.
Chapter 6 viroids and prions
Chapter 6Virus and cancer Prepared by:Miss Putri Shareen Binti Rosman
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 cells DNA.
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 Viruses• Oncogenic DNA Oncogenic RNA Viruses viruses Retroviridae – Adenoviridae – Herpesviridae Viral RNA is – Poxviridae transcribed to DNA – Papovaviridae which can integrate – Hepadnaviridae into host DNA HTLV 1 HTLV 2
Oncogenic viruses Brief background on cell cycle factors Rb and E2F example Enquist et al., Principles of Virology, ASM, 2004Example: DNA damage during G1P53 recognizes DNA damage and activates P21 (p53 recognizescertain types of DNA mismatches)P21 binds and inactivates the cyclin-CDK complex which hasalready begun to be produced in response to different signalsDNA repaired, p53 decreases, P21 no longer blocks cyclin-CDK,cell cycle progression
• 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 proteinsHPVn Enquist et al., Principles of Virology, ASM, 2004
Prions•Prions are “infectiousproteins”• They are normal bodyproteins that getconverted into analternate configuration bycontact with other prionproteins• They have no DNA orRNA•The main protein involvedin human and mammalianprion diseases is called“PrP”
Prion Diseases•Prions form insolubledeposits in the brain•Causes neurons torapidly degeneration.•Mad cow disease(bovine spongiformencephalitis: BSE) is anexample•People in New Guineaused to suffer fromkuru, which they gotfrom eating the brainsof their enemies
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
Other Viral Treatments•Interferon are naturallyoccurring proteins madeby cells to fight viruses•Genetic altering ofviruses (attenuatedviruses)•Antiviral drugs (AZT)•Protease inhibitors –prevent capsid formation
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)