Oncogenic Viruses Flashcards
(23 cards)
What percentage of cancers are caused by viruses?
15-20%
Viruses are the leading causes of which types of cancer?
Liver, cervical
What are the general mechanism by which viruses cause cancer?
Activate signalling pathways (cytokines)
Release cell cycle control
Infected cell destruction/clearance leads to unplanned regeneration
Why is the presence of viral genomes in a tumor not sufficient to say the virus caused the tumor?
It may be a coincidental spot of replication of the virus
It may be due to contamination of the assay
What are the epidemiologic criteria to be considered a cancer-causing virus?
Coincident geographic distribution of infxn, cancer
Higher incidence of viral markers in cases vs control references
Viral markers should precede cancer
Reduction in infection rats should reduce cancer rates
What are virologic criteria to be considered a cancer-causing virus?
Virus should transform cells in vitro
Virus genome present in tumor but not normal cells
Tumor induction in experimental animals
What are the six known human cancer viruses?
Human T-Lymphotrophic Virus Type 1 (HTLV1) KSHV EBV HPV Hep B Hep C
What is the difference between immortalized cells and transformed cells?
Immortalized cells retain original properties but grow indefinitely. Transformed cells are immortalized but lose many growth properties.
What were early viruses identified to cause cancer?
Avian Leukemia and Rous Sarcoma Virus
What are v-oncogenes?
Oncogenes contained in the viral genome that are transducing agents themselves, leading to rapid cancer formation.
What are c-oncogenes?
Oncogenes or proto-oncogenes in the human genome that can be activated to overstimulate by a virus.
What are transducing oncogenic viruses?
I.e. Rous Sarcoma Virus
Contain v-oncogene
100% of tumor formation
Rapid tumor formation
What are Nontransducing oncogenic viruses?
No v-oncogene, but can activate c-oncogenes via integration
Intermediate tumor time
High rate of tumor formation
What are nontransducing, long latency oncogenic Viruses?
HTLV1
Contain a v-oncogene unrelated to c-oncogenes
low rate of tumor formation
months to years to tumor formation
Through signaling pathways, explain how dna and rna tumor viruses can cause cancer.
They can increase/dysregulate kinase cascades, leading to increased cell division.
Can upregulate gene expression by introducing new transcription factors
What is a principal difference between v- and c-oncogenes in terms of activity?
V-oncogenes are always active.
What is the result of a v-oncogene that is always on?
Loss of signaling control and inappropriate grwoth
How do nontransducing retroviruses work?
They use insertional activation. Strong promoters or enhancers located in virus genome lead to unregulated overexpression of nearby c-oncogenes
How does HTLV work?
A long-latency retrovirus, causing T cell leukemia and lymphoma. infects and transforms CD4 T cells, through Tax. Tax stimulates Ikk to cause Ikb degradation, freeing NFkB to direct transcription. Leads to immortalization of T cells with transformation as well.
Explain EBV
Latent in B cells and leads to burkitts lymphoma and hodgkins lymphoma, and NPC
LMP1 activates kinase cascade that localized NFkB, which causes nuclesu to immortalize
What is KSHV?
Kaposi’s sarcoma, encoding several oncogenes that produce cytokines resulting in transformatino. Mess up GPCR.
Alters cell control, through v-cyclin production, activating cdk6
What is HPV?
Undergoes lytic replication in some cells. Others don’t allow lytic activity, so it transduces them. Integrated into host dna.
E6 BINDS TO P53
E7 BINDS TO RB (inactivating It)
How do hepbc work?
The constant clearance of infxted cells leads to unintended uncontrolled proliferation and cancer