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Flashcards in Oncogenesis Deck (25):
1

Does viral oncogenesis occur with immunosuppression or with chronic inflammation?

Both

2

how do viruses cause cancer?

indirectly--for hepatitis B and C
directly--papillomavirus

3

How do viruses directly cause cancer?

DNA viruses can cause cells to enter S phase for their own benefit--but if virus doesn't complete its life cycle and kill the cell, then viral proteins cause cell to override normal controls on growth

4

What viruses are associated w human cancer

hepatitis B
hepatitis C
EBV (herpesvirus)
HHV8 (herpesvirus)
HTLV1 (lentivirus)-T cell leukemia
HPV (papillomavirus)

5

Where does papillomavirus infect?

cutaneous and mucosal epithelia in hands, feet, anogenital tract

6

genome of papillomavirus

small
circular
double stranded DNA

7

Describe HPV early and late genes

early: E1, E2 mediate replication and transcription of viral DNA. E4 helps virus egress. E5,6,7 deal w cellular growth

Late: L1 and L2 make up the capsid

8

What do E6 and E7 do?

neutralize p53 and Rb, the brakes of the cell cycle

9

What can a wart formed from HPV infection result in?

resolution, or latency
OR
transformation

10

Where does HPV initially infect on a tissue level?

basal

11

Where does virion assembly and release occur for HPV?

in the cornified, apical layers of epithelium

12

how does HPV change the tissue morphology?

normally, only stratrum basale cells replicate. but HPV stimulates the cell cycle and causes cells in stratum spinosum to replicate--causes cells to be cube shaped still in more apical layers and an overgrowth of tissue

13

What is the role of Rb protein?

brake that prevents cell from going into S phase.
when there's enough CDK/cyclin in G1, Rb is phosphorylated and inactivated

14

What does E7 of HPV do?

Binds to Rb and tags it for degradation

15

What does p53 do?

activated by inappropriate entry into the cell cycle
causes synthesis of CDK/cyclin inhibitors
stops cell cycle
also can induce apoptosis

16

What does E6 do?

recruits ubiquitin ligase, which targets p53 for degradation

induces expression of telomerase--cell immortality

17

What makes for high risk strains of HPV?

strong correlation btwn hisk risk and activity of E6 and E7 proteins

18

What is carcinoma with HPV associated with?

integration of the DNA into the host chromosome b/c it disrupts the E2 gene, which normally is a transcriptional repressor. now increased E6 and E7 expression

19

What causes cervical neoplasia?

Episomal HPV DNA and virus production

20

What causes invasive cancer?

integrated HPV DNA (however, no virus production)

21

What can you detect for someone with HPV infection?

initially, negative Pap
HPV DNA found
no E6/7 mRNA yet
L1 protein found

22

What diagnostic tests are used for cervical intraepithelial neoplasia and cervical carcinoma?

pap smear--cells that are rounded and appear in clumps

hybrid capture assay for detection of HPV DNA

23

Are there vaccines for HPV?

Yes-Capside protein L1--results in humoral immunity

24

What kind of structures do L1s form in the vaccine?

VLPs-virus like particles

25

What other cancers are HPV associated with?

penile cancers, vulvar cancers, anal cancers
25% of oropharyngeal cancers