Chapter 6 Virus 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 cell's 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 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

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.

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

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 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

Chapter 6 Novel acellular infectious agent copyright cmassengale

copyright cmassengale 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” copyright cmassengale

How a Protein Can Be Infectious Figure 13.22

copyright cmassengale 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 copyright cmassengale

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

copyright cmassengale Viroids Small, circular RNA molecules without a protein coat.RNA does not code any protein. Infect plants Resemble introns cut out of eukaryotic copyright cmassengale

Treatment for Viral Disease copyright cmassengale

copyright cmassengale 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 copyright cmassengale

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 copyright cmassengale

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)