Picornaviruses

Abstract

The picornavirus family consists of a large number of small RNA viruses, many of which are significant pathogens of humans and livestock. They are amongst the simplest of vertebrate viruses comprising a single stranded positive sense RNA genome within a T = 1 (quasi T = 3) icosahedral protein capsid of approximately 30 nm diameter. The structures of a number of picornaviruses have been determined at close to atomic resolution by X-ray crystallography. The structures of cell entry intermediate particles and complexes of virus particles with receptor molecules or antibodies have also been obtained by X-ray crystallography or at a lower resolution by cryo-electron microscopy. Many of the receptors used by different picornaviruses have been identified, and it is becoming increasingly apparent that many use co-receptors and alternative receptors to bind to and infect cells. However, the mechanisms by which these viruses release their genomes and transport them across a cellular membrane to gain access to the cytoplasm are still poorly understood. Indeed, detailed studies of cell entry mechanisms have been made only on a few members of the family, and it is yet to be established how broadly the results of these are applicable across the full spectrum of picornaviruses. Working models of the cell entry process are being developed for the best studied picornaviruses, the enteroviruses. These viruses maintain particle integrity throughout the infection process and function as genome delivery modules. However, there is currently no model to explain how viruses such as cardio- and aphthoviruses that appear to simply dissociate into subunits during uncoating deliver their genomes into the cytoplasm.

Viroporins: structure, function and potential as antiviral targets

“…The second viroporin encoded by enteroviruses, VP4, is retained on the inside of the virion particle until internalization and endosomal acidification begin the process of uncoating (Tuthill et al, 2010). Interestingly, the potential for the formation of channels at the fivefold vertices of a variety of non-enveloped viruses was previously predicted from analysis of crystallographic studies, suggesting functional conservation (Kalko et al, 1992).…”

Triatoma virus structural polyprotein expression, processing and assembly into virus-like particles

“…Foot-and-mouth disease virus (Goodwin et al, 2009), Enterovirus 71 (Hu et al, 2003), Poliovirus (Hellen & Wimmer, 1992) and Rhinovirus (Palmenberg, 1990). Picornaviruses also possess (+)ssRNA genomes but, unlike dicistroviruses, they harbour a single ORF encoding all the structural and non-structural polypeptides (Tuthill et al, 2010). In most picornaviruses, genome translation gives rise to a single polyprotein that is self-processed by the 2A-proteinase domain releasing a series of polypeptides, including the P1 capsid precursor polyprotein.…”

You Cannot AlwaysWin: Molecular Bases of the Resistance of Picornaviruses to Win Compounds

“…the viral genome is translated into a single polyprotein precursor, containing one structural and two non-structural domains, which is subsequently cleaved into mature protein products by proteases encoded within the viral genome. the VP1-4 mature proteins are produced by the proteolytic cleavage of the n-terminus of the precursor protein, the products never actually becoming physically separated (20,28). VP1-3 proteins essentially have the same basic structure, a beta-barrel consisting of eight β-strands linked by loops of variable length.…”