LF213 - Virology
Poliovirus
Picornaviruses
Picornaviruses are very small viruses
- Single stranded positive sense RNA (Baltimore Class IV)
- None enveloped icosahedral particle, 60 copies of VP1-4 (subunit )
- RNA typically 7-8 kb, single open reading frame
- Genome has covalently attached protein at 5' end (VPg)
- Cytoplasmic replication
- Replication typically cytopathic
- RNA-dependent RNA polymerase
Human picornaviruses
Genus
- Enterovirus
- Gepatovirus
- Kobuvirus
- Parechovirus
Species
- Poliovirus
- Coxsackie virus
- Echovirus
- Human Rhinovirus
- Hepatitis A virus
- Kobuvirus
- Parechovirus
Poliovirus replication
- Attachment
- Penetration
- Uncoating
- Biosynthesis
- Assembly
- Release
The primary determinant of poliovirus is the virus receptor. Cell infection is restricted to human and primate cells. Virus replicates in mouse cells but can't infect them. cDNA library transfer screen in murine cells led to PV receptor, which is CD155 (PVR) is a transmembrane anchor and lg superfamily member. Poliovirus has 5-fold axis attachment strategies.
Entry-role of receptors during infection
- Hook - FMDV, minor group rhinovirus. The receptor function to concentrate virions on the surface of the cell; genome uncoating achieved by other means
- Unzipper - Poliovirus, major group rhinovirus. Receptor binding triggers and leads to disassembly of virion-capsid.
Poliovirus has 12 vertices which can bind to 5 receptors. Receptor binding displaces pocket factor, increasing the flexibility of VP1, allowing VP4 to interact with membrane. This probably needs interaction with multiple CS155 molecules.
Genome replication and protein synthesis
Poliovirus has positive sense RNA which can act as messenger RNA. The IRES element directs polyprotein translation and inhibits host protein synthesis. Different viruses have different types of IRES but they have the same function.
In a 5'end dependent molecule eIF4e binds to eIF4G which binds eIF3 which is a ribosome so is needed for translation. IRES-dependent molecules bind directly to eIF4G instead. Poliovirus 3A and FMDV L can cleve eIF4G which inhibits 5'-cap dependent replication.
Pathogenesis
Many enterovirus diseases are due to secondary spread. They replicate in the intestines and then spread to the blood through lymph nodes. Poliovirus transmission is faecal-oral. The clinical features of poliovirus infection range from nothing to paralysis and death. 90% of cases have no apparent illness. ~8% of cases have abortive poliomyelitis with fever, headache or sore throat. Nonparalytic poliomyelitis occurs in 1-2% of cases, causing severe headache, neck stiffness. Spinal paralytic poliomyelitis occurs in less than 1% of cases with Weakness and flaccid asymmetric lower limb paralysis. Recovery from paralysis (often incomplete) can occur but there is ~10% fatality rate. Bulbar paralytic poliomyelitis (<0.1%) causes cranial nerve paralysis and may be fatal due to respiratory muscle paralysis. It has ~50% fatality rate.