Tumour viruses and carcinogenesis Flashcards
What proteins are likely to be encoded for by late viral genes?
Proteins involved in the packaging of the viral progeny
What is a common feature of viral genomes, given the amount of genetic information being packed into a small particle.
Overlapping of genes
By what mechanism do viruses induce cellular proliferation?
If the early genes of the viral genome are transcribed but the late genes are not (damaged?) then there is a latent, persistent infection; the cells don’t produce any viral progeny so won’t be killed. But, the early genes that are transcribed may induce cellular proliferation
How do DNA tumour viruses integrate into host cells?
Virus needs to activate S phase of the cell cycle to replicate viral DNA in the nucleus. Viral genomes integrate into host DNA.
What occurs if their is full replication of viral genomes?
Cell death
What occurs if there is defective virus keeping early genes or non permissive cells only expressing early genes
There will be cellular transformation
Different proteins of oncogenic viruses target common cellular pathways. Give examples of these pathways
- Block p53
- Sequester Rb
- Signal transduction
- Tyrosine kinase signalling
What is the main effect of the E6 viral protein
Degrade p53 - but has pleitropic effects
How does hepatitis C virus cause oncogenic mutations in liver cells?
Destroy mature hepatocytes which stimulates their regeneration from stem cells that may carry oncogenic mutations
What is the gag retroviral protein responsible for?
It wraps up the genome of the virus
What is the env retroviral protein responsible for
Protein responsible for forming the viral envelope.
What is the pol retoviral gene responsible for>
Produces enzymes required for RNA reverse transcription and integration into the host genome (reverse transcriptase and integrase, protease which chops up gag proteins which form the protein core).
What are the long terminal repeats at the 3’ and 5’ ends of the retroviral genome responsible for?
Contain promoter and enhancer sequences for switching on genes.
Why might the LTR be responsible for inducing an oncogenic switch in a host cell
- As the viral genome is integrated into the host chromosome, the LTR will induce the expression of host genes immediately downstream of the viral genome. If this an oncogene then this cell will proliferate. This requires a long, latent infection as the point of integration of the viral genome is random.
- If a host oncogene becomes spliced into the viral genome, whilst maintaining the gag, env gene, then the now viral oncogene will be part of the viral genome, and be passed on to its progeny. This is an acutely transforming retrovirus that can infect and transform host cells subsequently.
Where does cervical cancer develop?
At the transition zone between columnar and squamous epithelium.
