Viruses and cancer Flashcards
What is cancer?
uncontrolled proliferation of cells
Why does HIV preferentially integrate within genes/transcriptional units?
transcriptional units are the most ‘relaxed’ –> usually open and not wound in chromatin
What is transformation? What is a major characteristic of transformed cells?
a change in morphological, biochemical or growth pattern of a cell
major characteristic = immortal
What prevents normal cells from being immortal, how do cancer/transformed cells prevent this?
- normal cells differentiate and proliferate then stop because their telomeres get too short
- cancer cells can encode tolermerases to make their telomeres longer
What does it mean that viruses can cause transformation which is a single hit process?
only cells infected will display a transfomed phenotype
What phenotypes can transfomed cells display?
- loss of anchorage dependence
- loss of contact inhibition
- decreased requirements for GFs
- morphological changes
How can viruses indirectly cause cancer?
- prolonged inflammation
- may cause DSBs that are repaired incorrectly
Name some types of RNA viruses that cause cancer
- flaviviruses (e.g. HCV)
- retroviruses
Name some types of DNA viruses that cause cancer
- hepadnaviruses
- papillomoviruses
- adenovirus
- herpesvirus
- poxviruses
What was the first oncogenic virus discovered?
rous-sarcoma virus
What kind of virus is rous-sarcoma virus, what gene makes it oncogenic?
virus = retrovirus
gene = v-src
What is the difference between c-src and v-src?
v-src cannot be -ve regulated by phosphorylation at the C-term:
- truncated regulatory domain
- always active
Describe retrovirus helper virus coinfections
- retroviruses can package other incomplete retrovirus genomes if the incomplete genome as a psi packaging signal
- this way incomplete retrovirus genome like PRC II avian leukosis virus that lacks env can be packaged by a full infectious avian leukosis virus like rous-sarcoma virus –> RSV becomes the helper virus to PRC ll ASV
- when a replication defective virus genome is packaged by a different retrovirus it’s called an env pseudotype
How does the psi package signal work? Where is it located in the genome of retroviruses?
- psi package signal lies in front of the 1st splice donor site and just after the 1st LTR in the 1st bit of the gag gene
- forms an RNA stemloop structure recognized and bound by gag
how can v-oncogenes be grouped, what are the existing groups? Name an example for each group
Grouped based on common biochemical features:
1. GFs (v-sis truncated PDGF)
2. memb Rs (v-erb EGFR)
3. tyr kinases (v-src)
4. G proteins (v-ras)
5. intermediate relay (v-raf)
6. TFs (v-fos)
Do retroviruses have to encode a v-oncogene to mediate cellular transformation?
no - retroviruses can cause cellular genes to be disregulated or disrupt important cellular genes depending where they integrate their genomes
What is cis activation of a proto-oncogene?
virus integration induces ts of a proto-oncogne, turning into an oncogene (think integrating in the regulatory region, for example)
What is trans activation of a proto-oncogene?
virus proteins activate ts of a proto-oncogene (think like how TFs can activate gene ts)
Why are IL-2 and IL-2R proto-oncogenes?
IL-2 is a GF for T cells –> leukemia
what is an oncogene?
gene that, when mutated or expressed at high level, helps turn a normal cell into a tumor cell
What is a transinducing retrovirus?
v-oncogene is present in virus genome
what is v-src necessary for?
virus-induced cellular transformation and tumorigenesis
What are low risk HPV types and what do they cause? What are high risk HPV types and what do they causes?
- low risk (6 and 11) –> genital warts
- high risk (16 and 18) –> 70% of cervical cancers
What are HPV’s oncogene?
E6 and E7
