5 viral oncogenesis Flashcards
what virisus indirectly cause cancer?
how do they do it?
hep B and Hep C
Chronic infection causes cirrhosis, inflammation, tissue damage, high levels of cell division. This cycle vastly increases the probability that hepatocytes will develop mutations and chromosomal aberrations that derail their “growth control”.
what viruses direcltly cause cancer?
how?
HPV
Upon infection, some DNA viruses stimulate the cells to enter S phase of the cell cycle and ready themselves for DNA synthesis. The virus needs this environment for its own replication. If the virus does not complete its life cycle and kill the infected cell…..then the same viral proteins can continue to direct the cell to override normal controls on cell growth and divide inappropriately.
Merkel Cell Carcinoma
what has it been associated with?
it has been associated with causing cancer in immunosuppressed individuals.
what is the morphology of the papillomavirus?
it has a small circular double stranded DNA
what are the kinds of genes that the HPV encodes?
E and L
early and late genes.
HPV
what genes meadiate the replicationa nd transcription of the viral DNA?
E1 and E2.
HPV what encodes the Capsid?
L1 and L2
what are the genese that are for growth control and are associated with oncogensis?
E6 and E7
neutralize the major “brakes” that regulate the cell cycle – p53 and Rb – and
hence uncouples cell division from key regulatory controls
what does HPV stimulate the the growth of that normally woudlnt grow?
the spinosum layer.
what is Rb protein?
it is a brake that blocks the progression into the s phase.
it is inhibited when enough cdk has built up.
what protein of HPV binds to Rb?
e7
inhbiting the inhbitor of cell cycling.
what protein of HPV degrades p53?
the E6 protein degrades p53.
inihbiting the inhibitor of s phase or apoptosis induction.
what Hpv protein increases the telomerase activity?
E6
this allows the cells to maintain their telomerases and avoid senescence
♦Greater than 99% of all cervical cancer specimens show evidence of infection with “high risk” strains of HPV strains
[Low risk strains are associated with warts]
supprots the point that HPV causes cervical cancer.
p53 and Rb are called “tumor suppressor genes” – their loss or inactivation causes a predisposition to cancer formation.
- p53 is mutated in >50% of all human cancers
- Rb is defective in the germ line of patients with inherited retinoblastoma, and is altered somatically in many other cancers
integration of E6 and E7 into the host causes what to happen to E2?
what does this mean for the cell?
when E6-7 are integrated into the host
E2 is broken up and it allows the level of expression of E6 and E7 to go up.
E2 would usaully act as a transcriptional repressor.
what is the pathology track of HPV legions?
LSIL to HSIL
CIN 1 to CIN 2 to CIN 3
What diagnostic tests are used for CIN I, CIN II, and cervical carcinoma ?
pap smear
Cytological evidence of displasia or neoplasia; detection of koilocytotic
cells (vacuolated cytoplasm) which are rounded and appear in clumps
Hybrid Capture Assay for Detection, Strain Analysis, and Quantification of HPV DNA
how does the HPV vaccine work?
what kind of immunity is it?
once the vaccine has taken up its place what is the effect of it to stop the virus from coming in?
Capsid protein L1 induces protective humoral immunity
the L1 assemble into VLPs that assemble like virons and induce the appropriate immunological response.
antibodies present at mucosal surface
prevent incoming HPV from establishing infection
what kind of cenacer is HPV associated with?
cervicle cancers
Vaccination of pre-adolescent girls with a VPL vaccine
they reccomended that boys get that vaccine too.
HPV is also associated with the formation of penile cancers, vulvar cancers, anal cancers and ~25 % of oropharyngeal cancers
