Picornaviruses Flashcards
(39 cards)
What are picornaviruses?
- positive sense ssRNA viruses that replicate in the cytoplasm
- enteroviruses such as rhunovirus or polio
- hepatoviruses such as hepatitis A
- apthroviruses such as foot and mouth disease
What is the general structure of a picornavirus?
- non enveloped
- icosahedral particle made of 60 promoters
on the surface each made of 3/4 proteins - VP1, 2 and 3 form the viral capsid
- VP4 is inside the capsid and associated with the viral RNA
Describe picornavirus structure in terms of receptors
- continuous groove acts as a binding site for cellular receptors and antibodies
- some enteroviruses can bind to many receptors -> host trophism
- drugs can inhibit receptor binding by filling or blocking the groove
Why weon’t receptor-blocking drugs work on all picornaviruses?
some such as C15a don’t have a continuous groove to block
Describe the genomic organisation of picornaviruses
- genome encodes one polyprotein that is cleaved into multiple products
- 5’ end has a viral protein covalently attached
- 3’ end is polyadenylated like host mRNA
- the 5’ UTR has an internal ribosome entry site that binds ribosomes differently to eukaryotes
- structural proteins at the 5’ end
- 3’ end proteins involved in replication and evasion of the host immune response
Briefly describe the picornavirus replication cycle
- entry is poorly understood but doesnt involve afusion
- uncoated and polyprotein is translated
- processed by proteases
- replication complex forms and associated with host lipid membranes to prevent its degradation
- negative RNA strand is made + use to make more genome or for genome packing and release by cell lysis
What is the importance of picornavirus proteins 3C and 3D?
- viral protease that cleaves the polyprotein at specific amino acids
- viral RNA-dependent RNA polymerase
Describe polyprotein processing in picornavirus
- P1 is translated and cleaves itself
- translation occurs up until 3C which also cleaves itself and then the rest of the protein
- cis and trans cleavage
Why is polyprotein processing a good drug target?
- its a property specific to viruses
- knocks out or binds to proteases to stop the production of functional proteins
How does picornavirus turn off host protein synthesis?
- 2A cleaves host mRNA 5’ caps to prevent ribosome binding
- IRES allows binding of ribosomes in an alternative way that is not affected by the loss of 5’ caps
- viral mRNA becomes the only mRNA available to be translated by host ribosomes
What are enteroviruses?
- a type of picornavirus
- polio, rhinovirus
- usually not severe
Where does enterovirus infect and where does it shed?
- infects the oropharyngeal or intestinal mucos and is shed in the faeces
What are the most common symptoms of rhinovirus?
- febrile illness is seen but 90% of infections are asymptomatic
How does rhinovirus spread to other organs?
spread by viraemia to skin, muscle, brain etc
How is enterovirus linked with T1D?
- in some, the virus infects and releases viral and beta cell antigens
- in those genetically predisposed this can trigger T1D autoimmunity
- IFHI gene variants can lower the risk by 50% and is involved in picornavirus recognition and interforminterferonresponsesWha
What kind of virus is poliovirus?
- picornavirus - enterovirus
Where does poliovirus infect and where does it spread?
- infects the small intestine
- can enter the bloodstream leading to viraemia that’s usually asymptomatic
- but in >1% of cases the CNS is infected leading to paralysis and/or death
How was the sabin vaccine against poliovirus produced?
- live attenuated virus
- cultured from monkeys and purified
- blind way of making vaccines rather than targeting specific proteins
- all have mutations in the 5’ UTR (IRES) and some in structural proteins
What are the differences between mass vaccination (OPV) and ruotine immunisation (OPV and IPV)
Mass vaccination involves going to an area and vaccinating as many people as possible, it is cheaper and can lead to eradication.
Routine immunisation usually prioritises those at specific ages or circumstances and doesnt stop the virus from spreading especially when coverage in low income countries is so low
Why is routine immunisation coverage low in many developing countries?
storage of the vaccine is difficult in hot climates and there is year long transmission of the disease meaning many individuals will already be infected by the time the vaccinations come round
What is poliovirus vaccinatoin like in the UK~?
- inactivated vaccine used
- 5 doses throughout childhood provides protection and stops the spread
What are the challenges associated with the use of the OPV vaccine commonly used for mass vaccination?
- virus can revert back to virulence or combine with other enteroviruses
- can spread virus to others in places where polio has been ‘eradicated’ and in places where polio resurfaces it is shown to usually be due to vaccine dervied strains
- has become a threat to erradication
What progress has been ,ade in erradicating poliovirus?
- type 2 declared eradicated in 2015
- changed from a trivalent vaccine to a bivalent and type 3 was declared eradicated in 2019
- only 1 wild type poliovirus remains
- but now need to control the spread of virus caused by the vaccine
What is the novel type 2 OPV?
- OPV vaccine genetically engineered to stabilise mutations and improve the viral polymerase
- to reduce mutations and reversion back to virulence
