Viral Oncogenesis Flashcards
How may the immune system either suppress or promote tumorigenesis in the context of a viral infection?
The immune system can recognize and target tumor cells. Some cancers are “worse” in the immunosuppressed.
Chronic inflammation due to an immune response can increase cell turnover, promoting mutation and tumorigenesis.
Distinguish between a direct and indirect viral oncogenesis.
In either case, cell turnover is increased. The difference is whether that is a product of the virus’s actions (eg blocking a cell cycle checkpoint) or of the immune system (eg chronic inflammation killing hepatocytes).
Name 5 viruses that are known to cause carcinogenesis.
Human Papilloma Virus (HPV)
Epstein-Barr Virus (EBV)
Hepatitis B (hepadnavirus)
Hepatitis C (flavivirus)
Merkel Cell Polyoma Virus
Lentivirus
Other herpesviruses…
Human Papilloma Virus (HPV)
Is it icosahedral or helical?
Is it naked or enveloped?
What is its baltimore type?
Icosahedral
Naked
Type I (dsDNA)
Describe the sequential gene products of HPV.
E1/E2 mediate replication/transcription of viral DNA.
Note: E2 represses E6/E7 expression.
E4 disrupts structural proteins for egress.
E5 stimulates growth factor receptor.
E6/E7 disable tumor suppressor proteins.
L1/L2 are capsid peptides.
Describe the transformation that epithelia undergo during HPV infection.
While uninfected epithelium exhibits consistent layered structure (keratinized cells in the stratum corneum, with only cells in the stratum basal replicate). Post-infection, the stratum spinosum begins replicating, and the cornified layers are sloughed off.
A wart may form.
What cell cycle checkpoint does Retinoblastoma control?
How is it normally activated or inactivated?
What HPV product can inactivate it?
The G1 to S checkpoint.
It is always “active”, and is inactivated by a CDK/Cyclin via phosphorylation.
Rb is bound by E7 to induce progression to S-phase.
What is p53?
How is it affected by HPV?
p53 (“The guardian of the genome”) is a tumor suppressor gene that can halt cell cycle progression as well as induce apoptosis if conditions are appropriate.
HPV’s E6 protein ubiquitinylates it. Following degradation, cell lines are more likely to become immortal (50% of all human cancers!).
Describe the fate of viral DNA in an infection by HPV.
Initially, the DNA is maintained as an episome (non-integrated). Once integrated, E2 expression stops, E6/7 expression increase, and DNA amplification may occur.
Describe the sequential stages of an HPV-induced epithelial lesion.
At which point is HPV’s DNA fully integrated into host cell genomes?
LSIL: Mild infection, some dysplasia. May progress to…
HSIL: Moderate dysplasia. May progress to…
CIN: Severe dysplasia and pre-cancerous. May progress to…
Cervical cancer. Full integration, and no return.
How does a pap smear test for cervical carcinoma?
The smear contains epithelial cells. Examining them will reveal the level of dysplasia, also look for vacuolated cytoplasm (koilocytotic) and clumping.
Describe the hybrid capture assay method for detecting HPV DNA.
Take host cells, lyse them to release their genomes. Wash these nucleic acids with an RNA probe that is specific for HPV sequences. If HPV genetic material is there, it will light up with fluorescent antibodies for the hybrids.
What is the structure of modern HPV vaccines?
What is the difference between “Gardasil” and “Cervarix”?
They are L1 pentons–spontaneously assembling capsid pieces that are immunogenic.
Gardasil grants immunity to the 6, 11, 16, and 18 strains. Cervarix grants immunity to just 16 and 18.
