MCM 2-20 Viral Oncogenesis

Question 1

characteric shape, genome and mechanism of oncogenic viruses?

Answer 1

no characteristic shape, genome, or mechanism

Question 2

what is the characteristic target cell, patient, pathway of oncogenic virueses?

Answer 2

not any

Question 3

T/F, animal models are not reliable predictors of human effects of oncogenic viruses

Answer 3

true.

Question 4

6 features of human cancer cells

Answer 4

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

Question 5

growth of himan cells is controlled by genes. Three important ones?

what are they called?

Answer 5

myc - transcription factor
src - membrane signaling of growth factor binding
ras - signal transduction from surface receptors

called protooncogenes

Question 6

cell cycle is controlled by tumor supressor genes. Two important ones?

Answer 6

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.

Question 7

how can oncogenes become overexpressed in certain cancers?

Answer 7

by amplification, mutation, or translocations of the genes close to active promoters (burkitts)

Question 8

____ is often mutated in cancer

____ is sometimes mutated

Answer 8

p53 is often mutated, Rb is sometimes mutated

Question 9

What viruses target tumor suppressor genes?

Answer 9

tumor suppressor genes like P53 and Rb are targeted by DNA viruses

Question 10

cell transformation can be caused by _________ viruses

Answer 10

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)

Question 11

Oncogenic viruses are species specific (T/F)

Answer 11

true

Question 12

important protein in SV40 virus?

Answer 12

“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.

Question 13

oncogenic adenoviruses are species-specific (T/F)

Answer 13

True.

Question 14

important proteins/genes in adenovirus oncogenicity?

Answer 14

E1a and E1b are similar to T-antigen, same effects in ANIMAL cells. Always expressed in transformed cells.

no human tumors contain adenoviruses.

Question 15

viruses that cause cancer in humans

Answer 15

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

Question 16

HPV

Answer 16

closely related to SV40, contains e6 and e7 which can block p53 and Rb.

Low risk, Intermediate Risk, and High risk complications

Question 17

important genes/protein product of high risk HPV’s?

Answer 17

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

Question 18

describe high Risk HPV

Answer 18

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

Question 19

transfection of cells with e6/e7 leads to

co-infection with mutated ras leads to

Answer 19

immortalization

transformation

Question 20

E6 and E7 in the high risk vs low risk HPV infection

Answer 20

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

Question 21

2 crticial occurrences for HPV to become malignant?

Answer 21

1. accumulation of RAS mutation
2. 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.

Question 22

what does the HPV vaccine do

Answer 22

slows progression to CIN3. Suggested for pre-pubescent children

Question 23

burkitts lymphoma

Answer 23

malaria belt
pre-pubertal boys
maxilla
contains EBV and expresses genes continually
"starry night" histology

Question 24

naso-phayngeal cancer

what predicts tumors or recurrences?

Answer 24

endemic in china, vietnam, arctic

contains EBV and expresses genes continuallly
environemtal co-factors involved

IgA antibodies to EBV capsid antigen

Question 25

EBV lymphoma pathogenesis

Answer 25

the Q8-14 translocation puts the myc gene under control of an immunoglobulin promoter (which is always on).

Question 26

describe B-cell lymphomas

Answer 26

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

Question 27

Hepatitis B virus

Answer 27

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

Question 28

pathogenesis of HBV-lvier cancer association

Answer 28

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

Question 29

Human T-cell leukemia Virus

Answer 29

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

Question 30

Karposi's Sarcoma Herpes Virus KSHV

Answer 30

50% carrier rate in africa aids in western world tumors contain KSVH DNA and express KSVH proteins

Question 31

retroviruses can cause cancer in animals by

Answer 31

tranmission of activated oncogenes or by insertional activation of an oncogene

Question 32

DNA viruses can cause cancer through

Answer 32

effects of T-antigen or equivalent (SV40, adenoviruses, HPV e6 and e7) which target p53 and Rb genes

Question 33

human viruses that are involved in etiology of some cancers include

Answer 33

HPV, EBV, HBV, HTLV1/2, KSHV

Question 34

what human cancers have a virus-vaccine?

Answer 34

``` cervical cancer heptocellular carcinoma (liver cancer) ```

Question 35

only example of virus crossing species barrier to cause cancer

Answer 35

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.

Question 36

which of the following cancers can be prevented by a vaccine? Burkitt's, Kaposi's, Liver, none of the above

Answer 36

Liver