L3+4 - Picornaviruses Flashcards
Describe the picornaviridae family
A family of small, spherical, non-enveloped, RNA viruses, containing ~ 63 genera and 147 species.
Relatively small, linear, positive sense ssRNA genome that replicates in the host cytoplasm and encodes a polyprotein that is processed by a viral encoded protease.
Give some examples of characteristic members in some of the common genera
Some common genera:
Enterovirus - Polioviruses, enteroviruses, Rhinoviruses
Hepatovirus - Hepatitis A virus
Cardiovirus - Encephalomyocarditis virus
Parechovirus - Human parechovirus
Apthovirus - Foot and mouth disease virus
Describe the structure of a picornavirus particle
Naked icosahedral particle (27-30nm) composed of 60 protomers, each comprised of 3/4 proteins. VP1, 2 and 3 form the external capsid. VP4 is buried inside the capsid and is associated with the RNA.
Describe how host cell receptors bind to the picornavirus particle and give some examples of receptors and their ligands.
Canyon structure on external surface (continuous groove which makes up the binding site for host cellular receptors used in viral entry). This provides some protection against antibodies (only 1 arm of the antibody can fit inside the groove).
The host cell has many receptors such as PVR (binds PV), CAR (binds CBV), ICAM-1 (binds HRV major) and VCAM-1 (binds EMCV) that facilitate the entry of the virus into the host cell.
Describe how drugs have been designed to prevent host cell receptor binding to the virus.
Usually a pocket factor (typically a lipid) binds reversibly to the binding groove on the virus particle in order to provide some structural integrity. The receptor is still able to bind and causes a conformational change that facilitates viral entry into host cell.
However, the antiviral drug is able to displace the pocket factor and prevent interaction of the virus particle with the host receptor, therefore blocking viral entry.
Describe the genomic organisation of picornaviruses
Single strand positive sense RNA molecule (6.7-10.1kb) - mostly resembles mRNA and is infectious independent of the virus particle. Genome encodes a single polyprotein of 2100-2400 amino acids.
5’ UTR contains IRES element (internal ribosome entry site) and is modified by the covalently attached VPg protein (encoded by the virus itself). 3’ UTR is modified by polyadenylation.
Translated polyprotein contains P1 (produces structural proteins that form the capsid), P2 and P3 (produce non-structural proteins that are proteases or used in RNA synthesis).
Describe the life cycle of picornaviruses
Virus first attaches to host cell via interactions with host cell receptors. The mechanism of entry and uncoating of the virus particle is not fully understood (may enter fully in an endosome or may release its contents into the cell via a membrane channel).
Viral genome is then either translated into polyprotein or moved into a membrane vesicle to form a replication complex.
Translation:
Genome acts as mRNA and is translated by the host cell as normal to form a large polyprotein. This polyprotein is then cleaved into smaller proteins P1, P2 and P3 which are then further processed into structural proteins (P1) or proteins required for genome replication / evasion of host defences (P2 and P3).
Replication:
Viral genome forms a replication complex in a membrane vesicle. RNA-dependent RNA polymerase transcribes negative sense RNA template strands (intermediates in replication). These negative strands are then transcribed into copies of positive sense RNA (new viral genomes) as part of positive strand amplification.
Once the viral proteins have been produced and the viral genome has been replicated. New virus particles are packaged and released by the host cell via cell lysis. Many picornaviruses e.g. polioviruses are cytolytic so destroy the host cell.
Describe how the picornavirus polyprotein is processed.
