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Structure of picornavirus
- small viruses with RNA genomes
- T= 1
- simple, symmetrical capsid
Genome of picornavirus
one piece of RNA that is linear and positive sense
- There's one very small viral protein called VPg that functions in place of a cap at the 5' end. Then, there is one super long open reading frame. There is a short poly-A tail at the 3' end
- Designed to look and act like mRNA
What is the pro of having positive sense RNA
when you have DNA, simple injection does not start an infection. The biggest exception is with positive sense RNA. If injected, you can often get a viral infection because it can instantly make proteins. This is one advantage.
What is the con of having positive sense RNA
There is usually only room for one gene. It'll get transcribed right away, but you'll only get one huge protein. This causes a lot of structural and temporal problems.
How do viruses evade the problem of one gene leading to one huge protein?
How viruses have evolved to evade this problem: their genome is transcribed as a polyprotein that is cleaved into smaller, structural,a dn functional proteins that are used.
Proteinases help to cleave the large protein
What is an important feature of picornaviruses?
It is a naked virus with no envelope. They are fragile, can rupture, can be changed. With this, there is a tightly folded protein coat. They can survive in weeks on end and do not need immediate entry into the body
Genera of Picornaviruses
all genera have multiple species of Picornavirus to cause disease
We separate them by their genomes, but some do act similarly in relation to their genome
1) They are __.
2) Explain replication.
3) Most of these viruses do what?
1) enteric viruses--enter through mouth and nose
- 2) They replicate in a primary location and get into the bloodstream adn go to where they are going. If hepato, they go to the liver. Some can infect neurons, such as polio.
- 3) Most of these viruses get back into your blood and colon and are shed in stool
Poliovirus was the first time what?
an RNA-dependent RNA polymerase was ID'ed
The virus makes the polymerase
the idea that a polyprotein gets cleaved was discovered
internal ribosome entry site; getting the cells to make them
Genes and proteins
all genes are translated as single polyprotein followed by proteolytic cleavage
Three to four capsid proteins (VP1-4)
One to three proteinases
Six to eight replication proteins
Explain what makes polioviruses different in relation to receptors.
Most viruses have proteins that come out and bind to cellular receptors. Polioviruses use something that is a lot less common. They use depressions or loop regions that fit cellular receptors into them. That is how they recognize the host cells.
The virus structure comes togetehr wtih three proteins on the surface and one underneath
Explain further the surface of the picornavirus.
Capsid contains 60 copies each of proteins VP1, VP2, VP3, and VP4
VP1- all fold into a jelly roll, composed of an 8-stranded beta-barrel. VP4 is buried beneath the shell
Most of teh viruses affect certain cell types and certain parts of teh body. They have different receptors. A lot fall into three families
Explain genome entry.
Some, like rhinovirus and foot-and-mouth disease, enter via receptor-mediated endocytosis
Others udnergo conformational chagnes directly at teh cell surface upon binding to their receptor. Virions lose the small internal protein VP4, and the hydrophobic N-terminus of VP1 is extruded to the surface of the particle. The altered picornavirus virions may participate in the formation of a pore within the plasma membrane, allowing the genome RNA to pass directly from the virion through the membrane into the cytoplasm.
Explain what happens once the genome RNA is in the cytoplasm?
it must be translated by cellular ribosomes to produce viral proteins.
A small virus-encoded protein called VPg is covalently attached to the 5' end of genome RNA, adn a poly(A) tract of 30 to 100 nucleotides is present at the 3' end. Unlike most cellular mRNAs, the poly(A) tract of picornaviruses is part of the genome sequence and is not added by a separate poly(A) polymerase
What is the method for initiation of protein synthesis?
Cap-directed initiation is directed by the eIF-4F complex, which recruits a 40S ribosomal subunit to the capped 5' end of an mRNA. The 40S subunit scans the mRNA, searching for an AUG codon in an appropriate sequence context. Then a 60S subunit joins to form the 80S complex, and protein synthesis begins
How is translation stopped?
by the proteolytic cleavage of eIF-4G or by sequestration of the cap-binding protein eIF-4E.
Because picornavirus RNAs aren't capped...__
a novel mechanism is used to direct ribosomes to the initiation AUG codon. All picornaviruses initiate protein synthesis via an IRES that lies within the 5' noncoding region
entry into mouth
replication in pharynx, GI tract, local lymphatics
Hematologic spread to lymphatics and CNS
Viral spread along nerve fibers
Destruction of motor neurons
What are the outcomes of poliovirus infection?
- 90% asymptomatic
- 7% minor non CNS illness
- 2% aseptic meningitis 1% paralysis
When you have polio, what are you presenting with?
acute flaccid paralysis, which involves looseness and an inability to control that muscle
Your diaphragm becomes paralyzed. YOu lose the ability to inflate/deflate the lungs adn need an iron lung
- Reservoir: human
- Transmission: fecal-oral or oral-oral
- Communicability: 7-10 days before onset; virus present in stool 3-6 weeks
Whay was interesting about the occurrence of this?
People in the slums had a brief exposure to it. They were asymptomatic and fine.
People in cleaner places were not exposed and, as a result, with age, they may have been effected and had detrimental results
Why is it important to have an IRES?
it brings ribosomes in the absence of a cap, allowing the preinitiation complex to not be necessary.
Viruses have an IRES sequence. It has a structure that is enough to recruit the ribosomes, bring them to a start codon, and induce viral protein production
There are a couple of different types of IRES sequences. They look different but there are some conserved elements. WHat are they?
- they are all healvily base paired
- they have AC rich regions
- Have a GNRA
- Have a pyrimidine rich sequence close to the start codon
Explain cleave of the polyprotein
it is autocatalytically cleaved--once made, ti can break itself apart. Some parts of the proteina re active enzymes. They will break it into big chunks, which have messages for other cleavage. It's like a cascade