MCM 2-20 Viral Oncogenesis Flashcards
characteric shape, genome and mechanism of oncogenic viruses?
no characteristic shape, genome, or mechanism
what is the characteristic target cell, patient, pathway of oncogenic virueses?
not any
T/F, animal models are not reliable predictors of human effects of oncogenic viruses
true.
6 features of human cancer cells
make tumors if transplanted to animals undifferentiated immortal not contact inhibited resistant to apotosis absormal chromosomes
all these features can be induced experimentally by viruses
growth of himan cells is controlled by genes. Three important ones?
what are they called?
myc - transcription factor
src - membrane signaling of growth factor binding
ras - signal transduction from surface receptors
called protooncogenes
cell cycle is controlled by tumor supressor genes. Two important ones?
p53 - activated by DNA damage, stops cell cycle until repair or causes apoptosis. Prevents accumulation of mutations.
Retinoblastoma - inhibits the cell cycle by inhibiting E2F which stimualtes the cell cycle
Both p53 and Rb can shut down or slow the cell cycle.
how can oncogenes become overexpressed in certain cancers?
by amplification, mutation, or translocations of the genes close to active promoters (burkitts)
____ is often mutated in cancer
____ is sometimes mutated
p53 is often mutated, Rb is sometimes mutated
What viruses target tumor suppressor genes?
tumor suppressor genes like P53 and Rb are targeted by DNA viruses
cell transformation can be caused by _________ viruses
RNA or DNA viruses
RNA oncogenic viruses carry activated oncogenes OR insert promoter to activate an oncogene. RNA oncogenic viruses have to do with activated or activating oncogenes
DNA viruses degrade or block the cell cycle genes (inactivate p53 or Rb)
Oncogenic viruses are species specific (T/F)
true
important protein in SV40 virus?
“large T- antigen” for causing tumors cancer. Large T inactivates and binds p53 and Rb
T-antigen must be continually expressed.
T-antigen allows cells to proliferate without control
SV40 does not cause tumors in humans, but it does in hamsters.
oncogenic adenoviruses are species-specific (T/F)
True.
important proteins/genes in adenovirus oncogenicity?
E1a and E1b are similar to T-antigen, same effects in ANIMAL cells. Always expressed in transformed cells.
no human tumors contain adenoviruses.
viruses that cause cancer in humans
papillomaviruses - warts - cervical cancer
EBV - mono - burkitts lymphoma and nasopheargeal cancer
HEP b - hepatitis B - hepatocellular carincoma (liver cancer)
Kaposi’s sarcoma - Karposi’s sarcoma
Human T-cell LEukima Virus - Leukemias, lymphomas
HPV
closely related to SV40, contains e6 and e7 which can block p53 and Rb.
Low risk, Intermediate Risk, and High risk complications
important genes/protein product of high risk HPV’s?
2 proteins - e6 and e7 are early, nucleotide suequence is similar of t-antigen of SV40. these are the tumorgenic proteins
They have another protein E2 - suppressor, when expressed. Binds promoter of e6 and e7 to
E6 and e7 is upregulated at TATA promoter. E2 upregulation leads to down-regulation of e6/e7
describe high Risk HPV
E6 and E7 are similar to t-antigen of sv40 virus
E6 binds p53 and leads to degradation by ubiquitin pathway
e7 binds non-phosphorylated Rb, prevents its interaction with E2F
transfection of cells with e6/e7 leads to
co-infection with mutated ras leads to
immortalization
transformation
E6 and E7 in the high risk vs low risk HPV infection
in low risk, e6 and e7 are similar but with much lower affinity binding to p52 and Rb
level of illness depends on affinity that the proteins have for binding p53 and Rb
2 crticial occurrences for HPV to become malignant?
- accumulation of RAS mutation
- integration of HPV into host chromosome. HPV integrates at random site, but is cut at the E2 gene (which inhibits e6 and e7). When it integrates, lose function of E2, and allows over expression of e6 and e7.
what does the HPV vaccine do
slows progression to CIN3. Suggested for pre-pubescent children
burkitts lymphoma
malaria belt pre-pubertal boys maxilla contains EBV and expresses genes continually "starry night" histology
naso-phayngeal cancer
what predicts tumors or recurrences?
endemic in china, vietnam, arctic
contains EBV and expresses genes continuallly
environemtal co-factors involved
IgA antibodies to EBV capsid antigen
EBV lymphoma pathogenesis
the Q8-14 translocation puts the myc gene under control of an immunoglobulin promoter (which is always on).
describe B-cell lymphomas
most are EBV negative, rarely present and some gene expressed
seen in patients with aids or long term graft recipients (immonocompromised)
may regress if immune function restored
Hepatitis B virus
risk factor for human cancer, liver cancer is higher in areas of endemic Hep-B infection
lots of antigen (chronic infection) over long time (HBsAg+, HBeAg+) = lots of virus = high level of liver cancer risk
seen in people unable to clear out virus
pathogenesis of HBV-lvier cancer association
tumor cells contain integrated HepB but no consistent expression of viral protein and no activation of cellular oncogene
mechanims unclear, but when you extract Protein X and combine with mutated RAS oncogene in mice, causes malignancy.
Protein X does something, but is not a tumor supressor OR and oncogene
Human T-cell leukemia Virus
endemic in carribean areas, jamaican immigrants
very slow pathogenesis
No oncogene, TAX expression may be important
does not activate or carry an oncogene or tumor supressor
HTLV-1 is integrated into genome of all leukemic cells
TAX exprssion declines over time, but HBZ persists
genetic changes accumulate
Karposi’s Sarcoma Herpes Virus KSHV
50% carrier rate in africa
aids in western world
tumors contain KSVH DNA and express KSVH proteins
retroviruses can cause cancer in animals by
tranmission of activated oncogenes or by insertional activation of an oncogene
DNA viruses can cause cancer through
effects of T-antigen or equivalent (SV40, adenoviruses, HPV e6 and e7) which target p53 and Rb genes
human viruses that are involved in etiology of some cancers include
HPV, EBV, HBV, HTLV1/2, KSHV
what human cancers have a virus-vaccine?
cervical cancer heptocellular carcinoma (liver cancer)
only example of virus crossing species barrier to cause cancer
The only documented exception wherein a virus crosses the species barrier and causes cancer in humans is in the case of using modified mouse leukemia virus for human gene therapy. Almost half of the patients developed T cell leukemia due to insertion of the gene next to the LMO2 oncogene.
which of the following cancers can be prevented by a vaccine? Burkitt’s, Kaposi’s, Liver, none of the above
Liver
