11 Adenovirus Flashcards
what does matadenovirus infect
mammals, Species Human Adenovirus type C
what does aviadenovirus infect
birds
species fowl adenovirus A
what species is atadenovirus
ovine adenovirus
what species is siadenovirus
species frog adenovirus
what species if ichtadenovirus
sturgeon adenovirus A
where is human adenovirus - mastadenovirus frequently occuring
frequent cause of acute upper respiratory tract (URT) infections
responsible for 5-10% of the common cold
what does human adenovirus cause
cause epidemics, especially in military recruits
where does human adenovirus replicate
adenoid tissue
what is the therapy
Vaccine normally only given to military recruits to prevent epidemic spread
Risk to general population is low
why might adenoviruses be useful
easily manipulated and can have been used as viral vectors, for human gene transfer
what are adenoviruses used to study
transcription and translational control
what is the morphology of adenovirus
icosahedral
what is the shell of adenovirus like
composed of 252 units of which: 240 hexons (each with 6 neighbours) 12 pentons (each with 5 neighbours)
what is the adenovirus genome like
Linear, non-segmented, d/s DNA
where does the synthesis of genes occur in adenoviruses
on the l or leftward strand and also r the rightward strand
what process makes the products in adenovirus genome
Multiple products are made from each using a process called splicing-which was first discovered in adenovirus
what are the phases of expression in adenoviruses
immediate early (IE-E1A)
early (E) DNA replication
Late (L) gene expression
what occurs in adenovirus splicing
Adenovirus uses several splice donor and acceptor sites to allow multiple proteins to be made from a single gene-see across
what are the stages in adenovirus life cycle
- Attachment
- Penetration and Uncoating
- Early transcription
- DNA Replication (early replication of adenovirus)
- Late gene expression, production of viral capsids
- Virus assembly and release
what happens in the attachment stage
Fiber binds cellular receptor, CAR penton base binds integrins (internalization)
what mediates the penetration and uncoating stage
pentons which trigger phagocytosis into a phagocytic vacule
what happens in lysis of the penetration and uncoating stage
lysis then occurs releasing a spherical partially uncoated partial- pentons are released
what happens when the hexon protein is released in penetration and uncoating
Hexon protein are released and the viral core enters the nucleus through nuclear pores
what does adenovirus use in early transcription
Adenovirus uses host cell RNA polymerase and early mRNAs are transcribed from scattered regions of both strands
how are mRNAs processed in early transcription
by host cell capping, methylation, polyadenylation and (sometimes) splicing enzyme systems
what happens after mRNAs processed in early trasncription
then exported to the cytoplasm and translated – divide into IE and EARLY
what happens in Immediate Early Gene Expression in early transcription
- Transcription of the E1A gene- multiply spliced
- E1A works by interacting with other proteins not by DNA binding
- Necessary for transcription of all early genes and in general activation of the genome
what is E1A
transactivating transcription factor -turns on other genes
what happens in the Early Gene Expression: 3 goals all controlled by E1A
- induction of cells to enter S (synthesis) phase of the cell cycle providing an optimal environment for DNA replication E1A-E4
- synthesising gene products needed for DNA replication encoded by E2
- expression of genes involved in combating antiviral defenses
what does the DNA replication phase mark
start of the late phase
what does adenovirus encode in DNA replication
own DNA polymerase
what is the DNA replication like
continuous
no okazaki fragments
why is a ds structure needed for early replication of adenovirus
in order to initiate replication at the end of adenovirus = ends of the displaced single-strand is self-complementary and allows priming
how does priming in early replication of adenovirus occur
terminal protein
what is made in the late gene expression stage
production of viral capsids
Production of capsid proteins, including Fibre, penton, hexon
what regulates late gene expression of viral capsids
regulated by the major late promoter, from a single transcript
what does splicing allow in late gene expression stage
allows 18 separate mRNAs
what happens to the adenoviral messages in late gene expression
they are preferentially translated
what happens because of adenoviral messages being translated in late gene expression
it is translated at the expense of cellular message (cell is processing viral RNA over and above the host RNA) cellular message isn’t translated (host cell shut off)
what do all mRNAs have
tripartite leader
what does the mechanism of TC involve
eIF4F and eIF2a
what happens during virus assembly and release
- Empty Capsid proteins are assembled
- The viral DNA then enters the capsid via a packaging signal near the left side of the genome which binds to one or more capsid proteins
- Eventually lysis of the cell occurs and up to 1000 viruses are released per infected cell
what can happen when virus is released
can form inclusion bodies -the basis of persistent infections (called hidden or occult)
what messages are translated
Viral messages are translated while cellular messages are not
what were interferons discovered to do
discovered to block virus translation
what does the interferon receptor activate
two pathways
- synthase from dsRNA makes ATP
- induction of protein kinase
what does the IFN synthase activation pathway cause
activates ribonuclease L which causes mRNA degradation
what does the IFN induction of protein kinase activation pathway cause
dsRNA activates protein kinase causes eIF-2 phosphorlyation = inhibition of protein synthesis
when does protein synthesis occur
when eIF2, GTP and initator TRNA methionine in a complex forming the ternary complex – goes to the end of the RNA together with cap binding proteins – the eIF-4F bind to the cap and look for the correct AUG where it will start translation
what is eIF2
eukaryotic initation factor 2
when is energy released in eIF2 regulation adenovirus
translate and release eIF2 into cytoplasm and no longer bound to GTP now bound to GDP as energy release
what is needed for another translation round
GDP must be exchanged for GTP which is done by GEF (eIF2B)
eIF GDP to GTP is changed by GEF – is reversible reaction
what will stop translation
if get eIF2 phosphorylation will block the GEF and block GTP recycling
what is responsible for the phosphorylation of eIF2
enzyme PKR is responsible for the phosphorylation of the eIF2 – causing the initation reaction to become blocked
what binds to PKR to prevent polymerisation
small RNA transcript – VA RNA binds to monomers of PKR to prevent polymerisation and diamerization
what is the VA RNA role
block the activation of PKR by dsRNA thereby preventing the block in protein synthesis which would occur in it absence
