Tumor Viruses Flashcards
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”
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
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
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
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
papovirus characteristics
DNA, double stranded (circular), naked, icosahedral
produces 10 genes, all of which are essential for tumor growth
what are some examples of papoviruses?
papilloma virus- infects humans
polyoma virus- rodents
SV40- monkeys
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
what cells does HPV infect?
epithelial cells- no viremia- grows locally,
what does HPV cause
warts and condylomas (genital warts)
6 and 1 1- most common cause of condylomas
16 and 18- cause cervical cancer
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
what is another large cofactor for developing cervical cancer when infected w/ HPV
cigarette smoking
describe the gardisil vaccine
protects against 6, 11, 16, and 18
dead virus
given in 3 doses over 6 months to people 9-26
describe the cervarix vaccine
protects against 6 and 11 only
dead virus
3 doses over 6 months
do adenoviruses cause cancer in humans?
no- cause cancer in rats
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.
