Picornaviruse

Buffl

Molecular Virology

by Leonie P.

Baltimore Classification System (of viruses) repetition

Families of RNA-Viruses

Families of (+) Strand RNA-Viruses

Family of Picornaviruses - Morphology

Family of Picornaviruses – (Infectious) Genome

6.7 - 10.1 (kilobases) in length.
like most positive-sense RNA genomes, the genetic material alone is infectious; although substantially less virulent than if contained within the viral particle,
the RNA can have increased infectivity when transfected into cells.
The genome RNA is unusual because it has a protein on the 5' end that is used as a primer for transcription by RNA polymerase. This primer is called VPg genome

Digression: 5’-Cap

Digression: Cap versus IRES

An IRES initiates translation in a cap-independent manner#

Picornavirus “host cell shutoff”

- Picornaviruses have a protease activity that can cut one of the proteins of the initiation complex (eIF4G).

- This seriously affects the host cell’s ability to translate cellular (5’-capped) mRNA’s, but does not affect translation from the IRES

Polyprotein Processing

Replication Cycle

VpG

Picornaviruses have a viral protein (VPg) covalently linked to 5' end of their genomes instead of 7-methylguanosine cap like cellular mRNAs. Virus RNA polymerases use VPg as primer. VPg as primer uses both positive- and negative-strand RNA synthesis. Picornavirus replication is initiated by the uridylylation of VPg.

Quasispecies (Theory)

A viral quasispecies is a population structure of viruses with a large number of variant genomes (related by mutations). Quasispecies result from high mutation rates as mutants arise continually and change in relative frequency as viral replication and selection proceeds

Viruses with a RNA genome replicate with extremely high mutation
rates (no proof-reading mechanisms) and exhibit a significant
genetic diversity. RNA viruses exist as a mixture of mutants !

Picornaviruses Pathogenesis

transmission via droplets / smears

Picornaviruses Antiviral Therapy

Family of Picornaviruses – Reverse Genetics

Family of Picornaviruses – Species

grouping difficulties

Poliovirus – Disease(s)

Poliovirus – Epidemiology

→ 1909 Discovery of Poliovirus
→ 1939 Discovery of 3 Serotypes
→ Endemic (sporadic) paralytic poliomyelitis – known since millennia
Wild poliovirus cases have decreased by over 99% since 1988, from an estimated 350 000 cases in more than 125 endemic countries to 6 reported cases in 2021. Of the 3 strains of wild poliovirus (type 1, type 2 and type 3), wild poliovirus type 2 was eradicated in 1999 and wild poliovirus type 3 was eradicated in 2020. As at 2022, endemic wild poliovirus type 1 remains in two countries: Pakistan and Afghanistan.

Discovery of Simian Virus 40 (SV40)

1960: Discovery of SV40, a polyomavirus with oncogenic potential, as a frequent contamination

of monkey kidney cell cultures and of viral vaccines (e.g. polio vaccine) produced in monkey

cells. In the US some 98 million people received (SV40-)contaminated polio vaccine !

Poliovirus – Vaccination