Polyomavirus Flashcards
Why was the discovery of Polyomaviruses so important?
-1st biological entity to be fully sequenced
-1st TF, enhancer, nuclear localization sequence and polyadenylation discovered
true or false: sv40 is related to polioviruses
true
-it is because the vaccine for polio was made using monkey kidneys and the vaccine was contaminated with sv40 coming from the monkeys
True or false the vaccine for polio cause a huge rise in cancers in the 50s
not really it def has developed cancers in some people but not as much as people anticipated
tho very oncogenic for mouses
facts about the polyomaviruses:
-non-enveloped
-icosahedral
-45 nm in diameter
-dsdna 4.5-5.5kb
-circular dna
what are the 2 main polyomaviruses in humans
BK virus: kidney epithelium: hemorrhagic cystitis, ureteral stenosis and allograph failure
-JC virus: kidney epithelium and brain oligodendrocytes: progressive multifocal leukoencephalopathy
which polyomavirus causes tumors in athymic mice
mouse polyomavirus
true or false: polyomaviruses are dangerous for most poeple
false: it is more dangerous for immunocompromised people like people who have aids
JC virus
-most important in humans
-known for being dangerous during the aids crisis
Progressive Multifocal Leukoencephopathy (PML)
-5% of AIDS patients have PML
-Is fatal in about 50% of those cases
-can cause dementia and change of personality
BK virus
Common early childhood infection.
Can cause mild respiratory or urinary track
disease. Viral DNA is found associated with some types
of cancer.
Merkel cell polyomavirus (MCV)
-Recently discovered in 2008. Causes most cases of
Merkel Cell Carcinoma.
-Mostly seen in AIDS patients. cause by immunosupression
-Merkel cells are cells associated with sensory neurons
-5y survival rate
which vaccine did sv 40 contaminated
the salk polio vaccine
true or false: polyomaviruses are self assembled
true
what makes up the structure of polyomaviruses
there is VP1 that makes the outside of the capsid
-VP2 and 3 are more inside and they stick everything together
-it also has histones from the host that wind up the DNA in the capsid
facts about the polyomaviruses genome
-they pretty much have the same genome structure (JCV, BKV and sv40)
-well conserved areas like the non-coding regulatory region
-the RR serves as a promoter for the activation of early and late genes (bi-directional)
-It also helps with the regulatory regulation (the early genes help set up the late transcription so that it is more efficient)
Functions of virus encoded polyomaviruses proteins:
Early region:
-Large T antigen708
Initiation of viral DNA replication
Stimulation of host DNA synthesis,
Regulation of transcription
-Middle T 421 Cell transformation
-Small T 174 Efficient viral DNA replication (PP2A
binding)
Late region
-VP1 362 Major capsid protein, attaches to
cellular receptors
-VP2 352 Minor capsid protein
-VP3 234 Minor capsid protein
-Agnoprotein 62 Release of viral particles
What are the three ways for polyomaviruses to enter the cell
-macropinocytosis
-Clathrin coated pit (most common)
-Caveolea (there is no endosome, the sort of sac stays ph neutral)
Where do SV40 binds?
it binds to glycolipids which are pretty much on everycell
-even tho it is low affinity there is a lot of small interactions so it is good at infecting almost any cells
which type of receptor does JCV binds
serotonin receptors
True or false: BKV uses clathrin coated vesicles
false it used caveolae
w does polyomaviruses go to the nucleus
it uses actin cytoskeletons
why is the SV40 LgT protein so important
-large T antigen sets up the virus replication so that it is more efficient
-since target cells are not actively dividing it needs to trigger the S phase
-it binds to RB
-has a pol a, rb, chaperone, p53,p300 binding domains
-it a part uses ATP activity for the helicase domain so that it can unwind the DNA properly
what is the name of the highly conserved region in polyomaviruses
COre origin TAg binding site 2
-it is the central perfect palindrome
how did polyomaviruses solve the end replication problem
by having a circular DNA there is no gap in the lagging strand
-at the 3’end for humans we use the telomerase to put telomeric reoears which are throwaway sequences that we can get rid of easily
is the name of the motif which binds to RB
LXCXE
-it binds to rb to free E2F so that it can activate S phase
-it is a highly conserved region in other viruses like HPV
-it is used by a lot of oncogenic DNA viruses to initiate S phase and bind RB
