Unit 3- Cancer Virology Flashcards
Why study viruses in cancer bio?
- oncogenic viruses cause 15-20% of cancers
- viruses = vectors for gene therapy/viral immunotherapy
What are viruses?
- submicroscopic (20-300 nm) infectious agents that cause disease
- consist of core DNA/RNA and surrounded by protein coat
What is the criteria constant among viruses?
- only 1 type of nucleic acid genome (DNA or RNA)
- virus reproduces from nucleic acid/ does not grow
- lack enzymes for energy metabolism
- use host ribosomes/ tRNA for protein synthesis
What is the life cycle of a DNA virus?
- entry into cell/ uncoating of DNA genome
- DNA replication/ Transcription to make RNA (protein coat)
> assembly of progeny virus/ exit from cell
endpoint = production of 100s of virus particles that infect new cells
Louis Pasteur/ Robert Koch classified infectious agents into what 2 categories depending on their behaviour during filtration?
Bacteria- trapped in pores of filters
Viruses- small enough to pass through filters
Who founded the discipline of tumor virology/ how?
Peyton Rous- RSV = Rous Sarcoma Virus
- carcinogenic agent was filterable (had to be virus)
What is cell transformation?
- conversion of a normal cell > tumor cell
- viruses can transform cells
What is interesting about RSV/ cell transformation?
CEFS (chick embryo fibroblasts) infected at permissive temp (37)
> cells became transformed
CEFs infected at non-permissive temp (41)
> cells reverted to normal phenotype
- continuous action of viral protein is required to maintain transformation/ RSV is not a ‘hit and run” affair
- transformation status depends on continuous influence of RSV
What is SV40?
SV40 = simian virus 40 (dsDNA virus)
- DNA integrates into host cell chromosomal DNA
> tumor virus genomes persist in virus-transformed cells
How do retroviral genes become integrated into chromosomes/ DNA of infected cells?
Retrovirus-RNA genome > replicate via DNA intermediate
Reverse Transcriptase- makes DNA/RNA then DNA/DNA
- integration of DNA copy into host chromosome
- transcription to make RNA > assembly of new virus particles
How do retroviruses like RSV exploit/ kidnap cellular genes?
- cellular genes like src can be converted into potent oncogenes following remodeling by a retrovirus
(v-src carried in RSV but src is a normal gene) - can also pick up/ activate cellular proto-oncogenes
How do retroviruses activate proto-oncogenes > oncogenes?
- insert genome adjacent to proto-oncogenes
- close association leads to uncontrolled proliferation
Do viruses set out to cause cancer?
no- byproduct of their replication strategy
- viral proteins target processes that control cell division/ apoptosis
What are the tenets of viral carcinogenesis?
- viruses can cause tumors in animals/ humans
- tumor viruses establish persistent infections in natural hosts
- host factors are determinants of virus-induced tumorigenesis
- viruses are seldom complete carcinogens
- virus infections are more common than virus-related tumor formation
- long patent periods between initial virus infection/ tumor appearance
- viral strains may differ in oncogenic potential
- viruses can be direct or indirect-acting carcinogenic agents
- oncogenic viruses module growth control pathways in cells
- viral markers are usually present in tumor cells
- 1 virus can be associated with more than 1 type of tumor
What are mechanisms of viral carcinogenesis?
- virus can carry oncogene ex) RSV expressed truncated src
- virus can integrate into chromosomes/ activate oncogenes
- virus can encode transforming genes > block normal protein function
- virus can cause carcinogenesis indirectly by damaging tissues
