Viruses and Cancer Flashcards
(25 cards)
Rous Sarcoma Virus
caused cancer when given back to a chicken
had etra “src” gene accidentally stolen from host cell - not required for virus multiplication but for transformation
v-src
Rous Sarcoma, captured c-src
c-src is normal cell gene that regulates proliferation (protooncogene)
protein tyrosine kinase
virus doesnt use
always on in host cell - mutated captured host in the mutated form!
how we learned about proto-oncogenes
c-onc
protooncogenes
generally encode proteins that reg cell growth or differentation
v-onc is usually mutant, constitutively active proteins expressed at high levels
viruses kidnapped mutated proto-onc genes
dominant GOF –> uncontrolled proliferation
HTLV-1
adult T cell leuemia
no proto-oncogenes
Tax - growth promotion –> transcriptional canges –> ATL, aneuploidy T cells)
cells usually don’t have Tax bc CTLs kill cells that express Tax
HBZ
protein that suppresses proliferation so adult t cell leukemia doesn’t lead to ATL (latent period)
TAX
protein that stimulates growth in T cells
in HTLV-1 virus
turn on Akt and NFkB for cell growth and cell survival
papovavirus
papilloma
polyomavirus
vaculating virus
small DNA tumor virus
stable
DNATV genome
small dsDNA genome
non-enveloped
replication initiator
stimulates proliferation (transformation)
REQUIRE host DNA replication proteins (DNA-dep DNA pol)
must advance quiescent cells into S phase
papillomaviruses
dsDNA
host and tissue specific
virus is sparse in most lesions
stratified squamous epithelia and HPV infection
basal layer replicates
move up layers and differentiates - lose ability to divide
virus infects basal layer and induces cell proliferation (viral genome maintained and segregated)
continue to divide as cells differentiate
infections virus is only made in outermost layer
CIN formation
from varying degrees of HPV induced proliferation in stratified squamous epithelia
test with pap smear
most individuals resolve
some progress to in situ carcinoma (invasive)
CIN1
very mild dysplasia
CIN2
moderate dysplasia
CIN3
severe dysplasia
in situ carcinoma
SCCA
invasive carcinoma
SIL
squamous intraepithelial lesion
low grade - CIN 1
high grade - CIN 2, CIN 3
VLPs
HPV vaccine!
virus like particles
take L1 gene from virus DNA and paste into another microbe
make L1 - self assemble - empty protein shell without DNA
looks like HPV virus
HPV DNA integration
no consequence or cervical cancer
dead end for virus!
loss of p53 (genomic instability)
interrupt E2 - can’t regulate cell replication (high E6, E7)
E6, E7
stimulate cellular proliferation
needed for productive viral growht
when genome is integrated, fuel cancer cell proliferation
Rb and HPV
tumor suppressor gene
cell cycle regulator - inactive when P (late G1), active when noP (quiescent - early G1)
unP - binds and inactivates E2F - no DNA replication!
E7 binds Rb –> releae E2F –> make cellular/viral replication proteins!
HPV and p53
tumor suppressor - at G1 phase
activates transcription of genes that arrest cell cycle and can promote apoptosis
E6 - binds p53 and sends it to proteasome to be degraded - cell can divide!
BK
early childhood - mild respiratory
lifetime persistance
immortalizes animal cells
tumorogenic in newborn animals
JC
isolated from immunosuppressed patient with demylinating disease PML
Merkel Cell Plyomavirus
merkel cell carcinoma - rare, aggressive skin cancer in elderly and immunosuppressed
found in a clonal form integrated
first integrated PyV with malignancy
