Lecture 13 Flashcards
True or false: PARVOVIRUS is a thicc virus
false
-it is a ssdna virus that is 4-6kb and is linear
aka real skinny
True or false all parvovirus needs a helper virus
false some do and some don’t
usually, they use adenoviruses
what is a condition that the parvovirus really needs for successfully infect a cell
it needs the cell to always be dividing
this is why it often infects the younger because their cells are dividing more often than older peeps
what are the 2 parvoviruses that mainly infects puppies and kittens
-canine parvoriruses infects puppies and can result in death
-Feline panleukopenia virus affects blood formation in cats and can result in death
Human B19
-infects erythroid progenitors aka red blood cells can result in anemia due to reduces red blood cells in circulation
-not life threatening only like fever and like rah
-dangerous if it is a pregnant woman that gets infected then it can result in birth defects or hydrops fetalis resulting in spontaneous abortion
-can also cause erythemainfectiosum aka fifth disease
What is the structure of basic parvovirus?
A 60 facets isocahedral
What are the names of the genes in parvovirus?
-NS(non-structural so like anything that helps with the transcription or translating) or also reo
-VP(viral protein aka what makes the structure) or cap
what is the use of the terminal end repeats
to help with replication and packaging
Whare does the parvovirus bind?
-B19: erythrocyte P antigen
-CPV/FPV: transferin receptor
-AAV: heparin sulphate, EGFR integinds (it depends which tissue it infects
lain the life cycle of parvovirus
ppt 12
explain parvovirus replication
ppt14
Transcription factor binding sites in MVM dsDNA
basically E2F from adenovirus will bind onto the parvoviruses so it turns on the replication of the virus and then the NS1 (rep78) that was made will also bind to the viruses gene to turn up even more transcription
Transcription factor binding sites in AAV dsDNA
basically MLTF from adenovirus (E1A)will bind onto the parvoviruses so it turns on the replication of the virus and then the NS1 (rep 78)that was made will also bind to the viruses gene to turn up even more transcription (for early)
and for late it is ATF from the adenovirus E1A
True or false: the parvovirus can like sit there in the genome of the host after integrated it
yeah it does that so that at some point there will be an oncogenic virus that’ll infect the cell it’ll be able to properly infect it
it also needs an adenovirus to lyse the cell so that it can get out
true or false: the capsid of parvoviruses is assembled using proteins
false, it self assembles
inverted repeats vs unique sequences parvoriruses
inverted: integrates for + or - strand in capsid
unique sequence: -strand in capsid
Is NS1/REP78 unifunctional or multufunctional
multifunctional:
1. Binding viral DNA to induce late gene expression of capid encoding genes.
2. ATPase dependent helicase to unwind viral DNA
3. Sequence specific endonuclease aka it makes the nicks
4. Also appears to retain cells in S phase
AAV as a gene therapy vector
-Does not cause disease in humans.
– Different AAV serotypes use a variety of receptors
so there is potential to target a specific tissue.
– Low toxicity
– Stable expression (has been observed for up to
one year) because it can integrate a cell
– Easy to genetically manipulate (small genome)
do you ise AAV as a gene therapy vector?
-so you have the virus and you take out the replicate and the capsid protein coding genomes
-you keep the promoter binding region and region where the nick is made
-you insert the gene with AAv helper and AD helper in an already E1 expressing cells
-now the recombinant virus that can deliver the gene in target cells
what is the problem with gene therapy using parvoviruses
it is that since the virus is small the gene also has to be small so that it can still fin into the capsid of the virus
Which of these diseases is not cured using gene therapy from parvovirus
– PKU
– Hemophilia B
– Duchenne’s Muscular Dystrophy
– Hemophilia A
– Aromatic amino acid decarboxylase (AADC) deficiency (Just
approved in Europe, Upstaza)
-crohn’s disease
– Mutation associated Retinal Dystrophy (FDA and health
Canada approved, Luxturna) First Gene Therapy Drug to be
approved for use in patients.
– Spinal Muscular Atrophy (FDA and Health Canada
approved, Zolgesma)
crohn’s disease
– Duchenne’s Muscular Dystrophy is thicc virus