Molecular biology

VIRION

Non-enveloped, spherical, about 30 nm in diameter, composed of a protein shell surrounding the naked RNA genome. The capsid consists of a densely-packed icosahedral arrangement of 60 protomers, each consisting of 4 polypeptides, VP1, VP2, VP3 and VP4. VP4 is located on the internal side of the capsid.

GENOME

Linear ssRNA(+) genome of 7.5-8.5 kb, polyadenylated, composed of a single ORF encoding a polyprotein. Viral genomic RNA has a viral protein (VPg) at its 5’. The long UTR at the 5’ end contains an internal ribosome entry site (IRES) type II. The P1 region encodes the structural polypeptides. The P2 and P3 regions encode the nonstructural proteins associated with replication. Encodes a N-terminal leader protease (L protease) in addition to the 3C protease. The shorter 3’ UTR is important in (-)strand synthesis.

GENE EXPRESSION

The virion RNA is infectious and serves as both the genome and viral messenger RNA. The IRES allows direct translation of the polyprotein. The polyprotein is initially processed by the viral proteases into various precursor and mature proteins to yield the structural proteins, replicase, VPg, and a number of proteins that modify the host cell, ultimately leading to cell lysis. Protein 2A causes ribosomes to skip formation of a peptide bond at the junction of the 2A and downstream sequence.

REPLICATION

CYTOPLASMIC

1. Virus attaches to host receptors, and is internalized in an endosome.
2. Upon endosomal acidification, the capsid opens a pore in the host cell membrane and the viral genomic RNA penetrates into the host cell cytoplasm.
3. VPg is removed from the viral RNA, which is then translated into a processed polyprotein.
4. Shutoff of cellular cap-dependent translation through the cleavage of the translation initiation factor eIF4G by the leader protease.
5. Replication of viral RNA takes place on membrane vesicles derived from the ER. A negative-sense complementary ssRNA is synthesized using the genomic RNA as a template.
6. New genomic RNA synthesized using the negative-sense RNA as a template is believed to be packaged into preformed procapsids.
7. Cell lysis and virus release.
8. Maturation of provirions by an unknown host protease.