Control Of Virus Replication - DNA Viruses Flashcards
What are the problems that DNA viruses face?
Synthesis of DNA usually only occurs in S phase
Problem of shortening of linear DNA genomes
What do DNA viruses have to do due to S phase synthesis?
most cells in our body are not replicating - viruses have to trigger the cell to go back through the cell cycle into synthesis phase
Why are DNA viruses associated with cancer but not RNA viruses?
Because DNA viruses have to trigger cells to go back thorugh cell cycle into synthesis phase which can lead to cancer
What are examples of DNA viruses?
Pox viruses
Herpesviruses
Adenoviruses
Papillomaviruses
What is the exception of DNA virus replication in the nucleus?
Poxviruses
They carry their polymerase required for DNA replication so they replicate in the cytoplasm
What is an example of a virus-encoded transcpirotn factor for HSV?
HSV-1 VP16 (alphaTIF)
What do virus encoded trasncpirotin factors do?
Binds cellular transcpriotn factors to activate immediate early genes
What phase of the cell cycle are most cells that viruses affect?
G0 phase
What is normally the case in G1 phase?
Transcription factor E2F is bound tightly to retinoblastoma protein
What needs to happen to get into S phase?
They need to disrupt the interaction between retinoblastoma protein and E2F and E2F will trigger transcription
What causes the trigger between G1 and S phase?
Phosphorylation of proteins by cyclin dependent kinases
How do viruses affect cyclin dependent kinases?
Some viruses make their own cyclin proteins that mimic host proteins that impact CDKs
Some viruses switch on signalling pathways to cause production of host cyclin D
What role do p53 and p21 have?
They have a strong regulatory role
P53 influences p21 which switches off CDKs
What do viral proteins do to p53?
Block it hence allowing unregulated CDK activation
What does adenovirus protein E1A do?
Block CDK inhibitors
What does SV40 large T act on?
Rb and p53
What happens when you get into S phase?
Lots of ribonucleotides synthesis genes are switched on
Rb and E2F become dislocated, dNTPs get made
What are the two ways of viral DNA replication?
Classical DNA replication or displacement synthesis
What is the problem with classical replication in virus genomes?
You need primers and without adding bits of DNa back on to make primer binding sites, every replication cycle, the genome would get slightly shorter
What type of virus has classical synthesis and why?
Polyomavirus SV40
Because it has a circular genome
How does initiation of SV40 replication occur?
Binding of helicases enzymes
Binds to an origin of replication, unwinds DNa, open up foot of replication bubble
Have one subunit in one direction, the other in the other direction
Eventually they go all the way round and hit each other and fall off because they are circular
What is the key difference between adenovirus and SV40 replication?
There are proteins attached to the end of the DNA molecule to avoid the end problem
What happens in adenovirus replication?
DNA binding protein binds to one strand, has specificity for a motif on positive strand, this unzips DNa, now have a protein on one strand and another protein on the other strand
What happens when adenovirus polymerase binds to one strand?
DNTPs come along ad that gets to this junction where DP isn’t captured, this is why it is called displacement synthesis. Now the polymerase will push this zippered DNA apart
Is DNA produced in two directions or one in displacement synthesis?
One direction only
What happens in displacement synthesis now there is a dead strand of DNa not being replicated?
The ends of the ss piece of DNa are complementary to each other so they stick together
Form a pan handles structure
This acts as a primer for synthesis of another positive strand
What cells does herpes simplex virus infect?
Epithelial cells
In HSV-1 genome, it has two segments, how many different genome rearrangement possibilities are there?
4 as both segments can be inverted
What are the 4 alpha, early immediate genes to remember for HSV-1 genome?
ICP0
ICP4
ICP22
ICP27
What does ICP0 do?
Potent transactivator of gene expression
What does ICP4 do?
Positive regulation of intermediate and late genes
What does ICP22 do?
Regulates expression of ICP0
What does ICP27 do?
Negatively regulates alpha genes and upregualtes late genes
What does binding and entry of HSV-1 virion require interaction with to start?
Heparin sulfate and HVEM, and nectin
What do LATs do?
Trigger virus replication to go from productive stage into latent stage
