ICL 1.2: DNA Viruses Flashcards
what’s the difference between how a virus with a small genome vs. large genome replicates?
small genomes usually use host machinery
viruses with larger genomes usually just make their own machinery
which families of DNA viruses are naked?
- parvoviridae
- polyomaviridae
- papillomaviridae
- adenoviridae
which families of DNA viruses are enveloped?
- herpesviridae
- poxviridae
- hepadnaviridae
how long do DNA viruses last?
DNA viruses often result in life-long persistent infections
they’re really good at sticking around by becoming latent or replicating in hidden areas
they manipulate the host cell so that is keeps replicating which could lead to tumor production…
are DNA or RNA virus genomes larger?
most DNA viruses have more genes than RNA viruses and allow DNA viruses to have more complicated life styles
DNA viruses appear better suited than RNA viruses to regulate and modulate expression of their and the host’s genes
what are non-essential genes?
genes for host immune response interaction
these are the ones we can mutate with drugs and it won’t effect the virus at all!
all these genes do is make it easier for the virus to replicate or stick around longer in the cell but they aren’t involved at all in the replication or structure of the virion
we can use this though to engineer viruses by deleting the non-essential proteins and putting in other struff – this is hard to do in viruses that have a small genome though
how does RNA synthesis work?
RNA synthesis aka transcription!!
it is primer independent and requires RNA polymerase and ribonucleotide triphosphates (rATP, UTP, etc)
what are the 3 RNA polymerases?
polymerase I: rRNA - Class I genes are transcribed by RNA polymerase I
polymerase II: mRNA - Class II genes are transcribed by RNA polymerase II that is inhibited by low doses of alpha-amanitin
polymerase II: tRNA - Class III genes are transcribed by RNA polymerase III
which cells have transcriptional machinery?
all cells except RBCs have nuclear transcriptional machinery
which viruses use host polymerase II to synthesize mRNA?
all DNA viruses (except poxviruses) use the host polymerase II to synthesize mRNA in the nucleus of infected cells
viral DNA goes to the nucleus after uncoating
the viral DNA has promoters that direct polymerase II to make viral mRNA
which DNA virus doesn’t replicate in the nucleus of host cells?
poxvirus
it’s the only DNA virus that doesn’t replicate in the host nucleus and use RNA polymerase II
it instead forms a cytoplasmic pocket that it can replicate in
it can do this because it has a huge coding capacity since it’s geneome is so big so it can afford to do this
what are the 3 basic kinds of genes in DNA viruses?
- immediate early genes (IE genes)
- early genes (E genes)
- late genes (L genes)
IE genes –> E genes –> L genes
aka genes are categorized based on when they’re needed during virus replication
what are IE genes?
promoters for IE genes are not specific & are recognized in most cells – IE viral promoters are simple promoters, E & L promoters are complex
the DNA virus genome is being recognized really quickly once its in the nucleus by the host transcription factors that drive transcription of the genes marked with promoters
this permits the host transcription machinery to initiate transcription of IE genes
basically IE genes make regulatory proteins at the beginning of the infection that later help make E gene products
what do IE genes do?
IE gene products:
1. turn off expression of host genes that interfere with the virus and turn on host genes the virus wants to use
- turn on expression of E genes
- turn off their own expression once they’re done
what are E gene products?
they modify the host DNA replication machinery, or are DNA polymerases themselves, to allow for the synthesis of viral DNA
they modify the host translation machinery for selective production of viral proteins
they also act to modify the cell so it doesn’t die before the virus replicates
and finally, they modify the transcription machinery further to switch on transcription of the L genes and to turn off their own transcription.
so over all, E gene products are needed to replicate the virus genome and overcome host barriers to infection – they are involved in the synthesis of the virus genomes!!
what are L gene products?
L genes encode viral structural proteins!! aka the envelope, capsid, etc. stuff that gets packed into the virion
L gene expression requires E proteins and synthesis of viral DNA – we don’t express L genes till the very end because they’ll just get in the way before
L genes usually only occur after DNA replication!
is the adenovirus naked or enveloped?
naked! it has no envelope!
it has fiber knobs on their capsid that binds to the host cell receptor
what is the pathway through which the adenovirus enters the cell?
- virus binds to receptor on host protein via fiber knob on capsid
- entry and penetration and uncoating – this happens in a pH dependent manner!!
- genome gets through a nuclear pore so this is where the genome gets inserted into the host nucleus – this is actually where full uncoating happens because the nucleocapsid is getting squeezed through this pore and the genome is being stripped and seperated sorta
through what method does the adenovirus replicate?
strand displacement
how does strand displacement work?
- as soon as the genome is uncoated from the capsid, we have the free genome which has terminal repeats
- an early protein from adenovirus binds to one end of the dsDNA of the adenovirus and splits the strands apart – this E2 also acts as a primer!
- a viral DNA polymerase binds to E2 primer and replicates the one viral DNA strand
they displaced strand behind
- the lagging strand connects to itself and forms a circle
- the E2 protein comes in again and displaces/splits open the circle and binds to the DNA allowing for DNA polymerase to come in again and now replicate the displaced strand
now you have 2 full copies of the viral genome!
whats the difference between the latent and eclipse period?
eclipse period is before we start to assemble virions
the latent period is where the virions are assembled but just haven’t been released from the cell
which virus family is the one with the largest DNA genome?
poxviridae
what is the correct sequence of events during an adenovirus infection?
- adsorption
- endosome acidification
- uncoating
- DNA synthesis
adenovirus doesn’t have an envelope so they don’t bud!!
is the parvovirus single or double stranded?
single stranded
are there more adenovirus genes or herpesvirus genes?
herpes virus!
what are the characteristics of the largest genomes?
DNA
so linear and double stranded!
what’s the simplified summary of DNA viruses?
- viral DNA enters the nucleus and host enzymes make mRNA from it
- viral mRNA is translated by host machinery to make viral proteins
- viral DNA is replicated using host DNA synthesis machinery
whats the problem that DNA viruses run into?
only cells that are making DNA have the machinery for DNA synthesis!
so, simple DNA viruses could only replicate in host cells that are cycling aka in S phase!!
however, most human cells are non-dividing, i.e. in G0….
so some viruses acutally figured out how to induce non-proliferating cells to enter the cell cycle and start proliferating while other viruses just encode their own DNA replication machinery so that they can replicate in non-proliferating cells
the good news is that drugs can specifically target viral vs. host DNA replication machinery
which DNA virus can only replicate in proliferating cells?
parvovirus
which DNA virus can induce non-proliferating cells to enter the cell cycle and start proliferating?
- polyoma virus
- papilloma virus
- adenovirus
which DNA viruses can encode their own DNA replication machinery and replicate in non-proliferating cells?
- herpes virus
2. pox virus
