Viral Oncogenesis

Question 1

percentage of the association of virus with a given cancer

Answer 1

15% to 100%

Question 2

what human cancer arises as an acute consequence of an infection

Answer 2

none – latency period between first infection and cancer development can be range from 15 - 40 years

Question 3

how common are viral infections that are linked to human cancers

Answer 3

extremely common - ubiquitous

Question 4

is there synthesis of the viral agent within the cancer cells

Answer 4

no

Question 5

what is mandatory for malignant conversion of a cell in relation to a virus

Answer 5

the virus must act on the host chromosome to cause mutation or the mutation must be within the viral genome

Question 6

what does it mean for some infectious agents to be indirect carcinogen

Answer 6

they play a role in cells becoming cancerous without actually persistence of their genes within the respective cancer cells

Question 7

what does it mean for chemical and physical carcinogens to act as mutagens

Answer 7

they cause genetic mutation (usually synergistically with carcinogenic infectious agents)

Question 8

what are the officially designated human carcinogens by DHHS and what cancers do they lead to?

Answer 8

Hep C - hepatocellular carcinoma
Hep B - hepatocellular carcinoma
HPVs - cervical, anal, and oral carcinomas and maybe non melanoma skin cancers

Question 9

18.6% of total cancer incidence is due to what 5 viral infections

Answer 9

HBV
HCV
HPV
EBV
Helicobacter Pylori

Question 10

what are some mechanisms done differently in tumor viruses

Answer 10

aberrant cell cycle, block apoptosis, cellular transcription development, chromatin remodeling, inflammation, metastasis, modulating signaling

Question 11

why is it thought that cancer development by viruses is an accident

Answer 11

it is not smart for virus to produce cancer because the cells in which they transform cannot make more viruses and release them

Question 12

in cells in which virus transform, what are the hallmarks causing cancer

Answer 12

loss of growth control, reduced adhesion, motility, invasion, ability to form tumors

Question 13

what do transformed cells (those transformed by virus) usually exhibit

Answer 13

chromosomal aberrations

Question 14

what type of viruses can transform cells

Answer 14

both DNA and RNA tumor viruses

Question 15

what happens when tumor viruses integrate their viral genome into the host chromosome?

Answer 15

production of more viruses by host diminishes or becomes absent

Question 16

what are human oncovirus replication and persistence strategies (hallmarks of cancer)

Answer 16

• find/create conditions for replication (induce the cell cycle, metabolic programming, inducing angiogenesis)
• ensure correct replication (recruit or inhibit DDR)
• maximize virus production (prevent apoptosis until virion matures, immune evasion)
• multiply latent episomes or provirus (cell survival, cell immortalization, cell proliferation)

Question 17

viral oncoprotein in EBV

Answer 17

EBNA-1

Question 18

viral oncoprotein in HPV

Answer 18

E6 and E7

Question 19

viral oncoprotein in HBV

Answer 19

HBx (important because it hits all pathways)

Question 20

viral oncoprotein in HTLV-1

Answer 20

Tax

Question 21

pathways that most tumor viruses go through

Answer 21

p53 and Rb

Question 22

proteins involved in papilloma and polyoma respectively (DNA tumor virus)

Answer 22

papilloma - E6 and E7

polyoma - Large T and small T antigen

Question 23

proteins involved in adenovirus and BK virus (DNA tumor virus)

Answer 23

adenovirus - E1A and E1B

BK - Large T

Question 24

proteins involved in SV-40 (DNA tumor virus)

Answer 24

large T

Question 25

what do DNA Tumor Viruses have in common

Answer 25

have sequences in common --> mutations in these regions abolish transformation capacity

Question 26

properties of DNA Tumor Viruses

Answer 26

* can transform cells or have lytic life cycle * often integrate into host genome * in transformation, often ONLY early genes are transcribed * these are genes that are also necessary for a PRODUCTIVE infection

Question 27

#1 virus associated STD

Answer 27

HPV

Question 28

how does HPV cause cancer

Answer 28

HPV infection (0-1yrs) --> low grade dysplasia (1-5 years) --> high grade dysplasia ( 1- 40 years) --> invasive cervical cancer

Question 29

mechanism of HPV associated carcinogenesis

Answer 29

HPV infection --> viral clearance --> type specific immunity HPV infection --> viral persistence --> viral clearance --> type specific immunity HPV infection --> viral persistence -->episomal or integration of viral DNA (overexpression of E6 and E7) --> increased in cell proliferation, decrease in repair --> mutation --> CIN --> invasive cervical cancer

Question 30

what does E6 and E7 target

Answer 30

p53 and pRb respectively

Question 31

ultimate B lymphocyte parasite

Answer 31

EBV (HHV4)

Question 32

symptoms of EBV

Answer 32

greater than 90% of those infected are asymptomatic but do shed for life

Question 33

what does EBV do

Answer 33

stimulate growth and immortalizes B cells in culture

Question 34

what carcinomas are EBV associated with

Answer 34

AfBL (african burkitt lymphoma), hodgkins disease, NPC, B cell lymphomas in patients with acquired or congenital immunodeficiencies

Question 35

what is the virus associated with Kaposi's Sarcoma

Answer 35

HHV-8 aka KSHV

Question 36

what is kaposi's sarcoma

Answer 36

tumor of the blood vessel walls that is usually common in those with HIV -- frequently detected in those with AIDS

Question 37

how does kaposi's sarcoma present

Answer 37

pink, red, or purple lesions on the skin or mouth