MCM 2-20 Viral Oncogenesis Flashcards Preview

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Flashcards in MCM 2-20 Viral Oncogenesis Deck (36)
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1

characteric shape, genome and mechanism of oncogenic viruses?

no characteristic shape, genome, or mechanism

2

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

not any

3

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

true.

4

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

5

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

6

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.

7

how can oncogenes become overexpressed in certain cancers?

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

8

____ is often mutated in cancer

____ is sometimes mutated

p53 is often mutated, Rb is sometimes mutated

9

What viruses target tumor suppressor genes?

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

10

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)

11

Oncogenic viruses are species specific (T/F)

true

12

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.

13

oncogenic adenoviruses are species-specific (T/F)

True.

14

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.

15

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

16

HPV

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

Low risk, Intermediate Risk, and High risk complications

17

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

18

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

19

transfection of cells with e6/e7 leads to

co-infection with mutated ras leads to

immortalization

transformation

20

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

21

2 crticial occurrences for HPV to become malignant?

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.

22

what does the HPV vaccine do

slows progression to CIN3. Suggested for pre-pubescent children

23

burkitts lymphoma

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

24

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

25

EBV lymphoma pathogenesis

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

26

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

27

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

28

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

29

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

30

Karposi's Sarcoma Herpes Virus KSHV

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

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