Tumor Viruses

Question 1

what does transformation mean?

Answer 1

cell can grow indefinitely and growth cannot be arrested. it requires less serum, does not exhibit contact inhibition, and is anchorage independent

is “tumorigenic”

Question 2

what is the mechanism by which viruses cause tumors

Answer 2

two ways:

RNA viruses will introduce, upregulate, or mutate proto-oncogenes

DNA viruses will degrade or sequester tumor suppressor genes

Question 3

how can you detect oncogenic viruses in tumors?

Answer 3

1. take cell free extract and inject into animal model/cells to see if tumors form

2 use fluorescent Abs, western blot, ELISA, etc. to look for viral proteins

3 use PCR, northern blotting, southern blotting, etc. to look for nucleic acids

Question 4

describe how the morphology of cancer cells differs from regular cells in vitro

Answer 4

regular cells grow flat, in an ordered way

cancer cells grow rounded, disordered

Question 5

describe the biochemical differences between cancer cells and regular cells in vitro

Answer 5

cancer cells have higher rates of glycolysis and glucose transport. they have lots of proteinases, but reduced fibronectin and actin

Question 6

papovirus characteristics

Answer 6

DNA, double stranded (circular), naked, icosahedral

produces 10 genes, all of which are essential for tumor growth

Question 7

what are some examples of papoviruses?

Answer 7

papilloma virus- infects humans
polyoma virus- rodents
SV40- monkeys

Question 8

describe papovirus replication. how is this related to its tumorgenic properties?

Answer 8

replication divided into early and late stages

early replication involves host RNA polymerase transcribing the T-antigen

T-antigen binds the origin of replication. host DNA poly recognizes and binds the T-antigen, beginning replication.

following replication, late replication starts and transcribe the viral capsids

viral capsids self assemble and cause lytic burst of cell

in addition to binding origin of replication, T antigen also binds and inactivates p53 and Rb tumor suppressors

Question 9

what cells does HPV infect?

Answer 9

epithelial cells- no viremia- grows locally,

Question 10

what does HPV cause

Answer 10

warts and condylomas (genital warts)

6 and 1 1- most common cause of condylomas
16 and 18- cause cervical cancer

Question 11

which strands of HPV cause cervical cancer? how?

Answer 11

16 and 18- they have oncogenes E6 and E7, which bind p53 and Rb respectively, targeting them for destruction and thus inactivating them

Question 12

what is another large cofactor for developing cervical cancer when infected w/ HPV

Answer 12

cigarette smoking

Question 13

describe the gardisil vaccine

Answer 13

protects against 6, 11, 16, and 18

dead virus

given in 3 doses over 6 months to people 9-26

Question 14

describe the cervarix vaccine

Answer 14

protects against 6 and 11 only

dead virus

3 doses over 6 months

Question 15

do adenoviruses cause cancer in humans?

Answer 15

no- cause cancer in rats

Question 16

how do adenoviruses cause cancer?

Answer 16

two important proteins:

E1A binds and inactivates Rb, p300, and CBP
also binds to transcription factors to initiate S phase

E1B upregulates E1A

Question 17

describe herpes virus characteristics?

Answer 17

DNA, double stranded, enveloped, icosahedral

Question 18

what herpes viruses cause cancer?

Answer 18

EBV and Kaposis sarcoma virus (HHV8)

Question 19

EBV cancer

Answer 19

causes burkitts lymphoma- a B cell lymphoma

causes tumors in jaw, heart, abdomen, but does respond to chemo

(can also cause nasopharyngeal carcinoma in Asia but mechanisms not understood)

Question 20

how does EBV cause cancer

Answer 20

extrachromosomal EBV genomes always found in b-cells

infection is latent, and integration is not required for transformation

translocation puts c-myc proto-oncogen under transcriptional control of an Ig- over expression

T-cell normally controls these B-cell except under immunosuppression or in immunocompromised individuals

Question 21

what are two important EBV genes that cause transformation

Answer 21

EBNA-2 transcriptional activator

LMP-1- CD40 analogoue

Question 22

where is Burkitts lymphoma found

Answer 22

equitorial africa- coincidence w/ AIDS and malaria

Question 23

Kapsois Sarcoma herpes virus cancer mechanisms

Answer 23

Kapsois sarcoma most common cancer w/ AIDS, but is uncommon w/o immunosuppresion

tumors present w/ multiple, pigmented, high vascular skin nodules. tumor cells express VGEF

viral genes: GPCR (VGEF) and LANA (cell growth)

Question 24

retrovirus characteristics

Answer 24

RNA, single stranded, positive sense, enveloped, helical

Question 25

essential retrovirus genes

Answer 25

gag- nucleocapsid proteins

pol- reverse transcriptase and integrase

env- envelop glycolipids

Question 26

retrovirus classification

Answer 26

divided into oncoviruses and lentiviruses (no cancer)

oncoviruses have 3 classifications:
transducing- have captured an onco-gene and insert it directly. transformation is short. usually cannot replicate

non-transducing- don’t have an oncogene, instead cellular oncogene is activated by provirus. replication intact. intermediate transformation time

non-transducing, long latency- long transformation. viral protein influencing transcription

Question 27

provirus

Answer 27

retroviruses are positive sense single strande RNA

RNA transcriptase converts the RNA into double stranded DNA and integrates it into host genome. this serves to make mRNA for future progeny and is called a provirus

Question 28

long tandem repeats

Answer 28

Reverse transcriptase adds regulatory elements to the ends of the DNA it creates

Question 29

describe retrovirus replication

Answer 29

enters cytoplasm. reverse transcriptase begins at primer tRNA, creating a RNA-DNA hybrid. RNase H degrades the viral RNA, and reverse transcriptase finishes the DNA.

DNA is longer because of LTRs. it moves into the nucleus and integrates, becoming a provirus

host DNA polymerase and replication machinary create and translate mRNA and viral proteins, eventually creating entire viral genome copies that can then leave

Question 30

RSV

Answer 30

rous sarcoma virus- transducing virus- transforms w/in 24 hours of introduction to chicken

encodes src oncogene (tyrosine kinase)

Question 31

what types of proteins make good protooncogenes

Answer 31

growth factors
growth factor receptors
kinases
G proteins
proteins that regulate transcription and regulation

Question 32

how do acute transforming viruses replicate?

Answer 32

they cannot replicate themselves because one of their 3 essential genes has been replaced with an oncogene.

if they are to grow, they need a helper retrovirus to coinfect the cell and provide the missing proteins

Question 33

what are the human carcinogenic retroviruses?

Answer 33

HTLV 1 and 2. they do not have oncogenes

Question 34

how is HTLV transmitted

Answer 34

blood, semen, perinatal (bodily fluid)

Question 35

where does HTLV infect?

Answer 35

mucous membranes- viremia- t-lymphocytes

Question 36

what does HTLV 1 cause?

Answer 36

adult t cell leukemia (.1% of infected, everyone else is usually asymptomatic. takes years)

Question 37

hepatitis B cancer

Answer 37

5% of hep b cases become chronic. 5% of those cases get liver cancer.

cause unknown, but hep viral genome integrates w/ host.

theories: inserts near proto-oncogene
has an oncogene
destruction and redevelopment of liver provides opportunities for errors

Question 38

what are the differences in how hepatitis b and retroviruses use reverse transcriptase

Answer 38

retrovirus is an RNA virus, and uses it to create DNA provirus that can integrate into the nucleus

hep B is a DNA virus. it creates mRNA copies of itself, which are then put into the capsid, and reverse transcriptase then generate the proper DNA format at the end of the lifecycle

Question 39

hep C cancer

Answer 39

20% of people with chronic hep C develop cancer. there is no oncogene and integration does not occur.