Tumor Viruses Flashcards by Drew Blake

what does transformation mean?

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

is “tumorigenic”

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what is the mechanism by which viruses cause tumors

two ways:

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

DNA viruses will degrade or sequester tumor suppressor genes

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how can you detect oncogenic viruses in tumors?

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

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

regular cells grow flat, in an ordered way

cancer cells grow rounded, disordered

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

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

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papovirus characteristics

DNA, double stranded (circular), naked, icosahedral

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

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what are some examples of papoviruses?

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

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

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

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what cells does HPV infect?

epithelial cells- no viremia- grows locally,

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what does HPV cause

warts and condylomas (genital warts)

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

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which strands of HPV cause cervical cancer? how?

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

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

cigarette smoking

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describe the gardisil vaccine

protects against 6, 11, 16, and 18

dead virus

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

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describe the cervarix vaccine

protects against 6 and 11 only

dead virus

3 doses over 6 months

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do adenoviruses cause cancer in humans?

no- cause cancer in rats

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how do adenoviruses cause cancer?

two important proteins:

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

E1B upregulates E1A

describe herpes virus characteristics?

DNA, double stranded, enveloped, icosahedral

what herpes viruses cause cancer?

EBV and Kaposis sarcoma virus (HHV8)

EBV cancer

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)

how does EBV cause cancer

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

what are two important EBV genes that cause transformation

EBNA-2 transcriptional activator

LMP-1- CD40 analogoue

where is Burkitts lymphoma found

equitorial africa- coincidence w/ AIDS and malaria

Kapsois Sarcoma herpes virus cancer mechanisms

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)

retrovirus characteristics

RNA, single stranded, positive sense, enveloped, helical

essential retrovirus genes

gag- nucleocapsid proteins pol- reverse transcriptase and integrase env- envelop glycolipids

retrovirus classification

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

provirus

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

long tandem repeats

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

describe retrovirus replication

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

RSV

rous sarcoma virus- transducing virus- transforms w/in 24 hours of introduction to chicken encodes src oncogene (tyrosine kinase)

what types of proteins make good protooncogenes

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

how do acute transforming viruses replicate?

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

what are the human carcinogenic retroviruses?

HTLV 1 and 2. they do not have oncogenes

how is HTLV transmitted

blood, semen, perinatal (bodily fluid)

where does HTLV infect?

mucous membranes- viremia- t-lymphocytes

what does HTLV 1 cause?

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

hepatitis B cancer

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

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

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

hep C cancer

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