Picornaviruses

Abstract

The name picornavirus is derived from pico for small and ribonucleic acid (RNA), denoting the chemical nature of the genome. Virions are nonenveloped icosahedral particles approximately 30 nm in diameter. The capsid is constructed from 60 copies of each of four structural proteins, which account for 70% of the particle mass and enclose the single‐strand genome of 7500–8500 nucleotides. The positive‐strand genome acts directly as a messenger RNA to template a single polyprotein product. This is subsequently processed by virally encoded proteases into mature active proteins. Several intermediate products have distinct functions to the final fully processed proteins. Replication of the genome is initiated by an uridylated peptide and proceeds via a negative‐strand intermediate template. Picornaviruses are among the smallest pathogens of vertebrates and are responsible for many important diseases in humans and animals.

Key Concepts

  • There are effective vaccines against polio, hepatitis A and foot‐and‐mouth disease viruses. In addition, movement control and slaughter is used to control foot‐and‐mouth disease. There are no licensed drugs for picornavirus infections.
  • Genome sequence comparisons have replaced biological and biophysical comparisons as the bases for classification within the family.
  • Picornavirus particles comprise 60 copies each of four structural proteins, which form a quasi‐T1 icosohedral capsid encasing the single‐strand RNA genome.
  • The picornavirus RNA genome functions as a messenger RNA to template the synthesis of a single polyprotein, which is posttranslationally processed by viral proteases.
  • Picornaviruses bind to cell‐specific surface receptors, and this interaction is an important factor in determining host and tissue specificity of each virus.
  • Picornaviruses cannot gain entry to cells by membrane fusion, as is the case for enveloped viruses, and require special mechanisms to breach cellular membranes and safely deliver the genome into the host cell.
  • Genome replication occurs in association with virus‐modified cellular membranes. Viral RNA templates complementary negative‐strand molecules, which in turn template multiple positive‐strand copies. The synthesis of all RNA molecules is initiated by an uridylated peptide primer.
  • The mechanisms of transmission of infection play key roles in the epidemiology of picornavirus infections.
  • Picornaviruses are responsible for a wide range of clinical diseases resulting from multiple factors such as receptor specificity, tissue‐specific susceptibility, virulence and the mechanisms of transmission.

Keywords: positive‐strand RNA; nonenveloped viruses; infectious disease; virus structure; virus replication

Figure 1. Evolutionary relationships of 50 taxa. Evolutionary history was inferred using the Neighbour‐Joining method. The optimal tree with the sum of branch length = 23.63528644 is shown. The tree is drawn to scale, with branch lengths in the same units as those of the evolutionary distances used to infer the phylogenetic tree. The evolutionary distances were computed using the JTT matrix‐based method and are in the units of the number of amino acid substitutions per site. The analysis involved 50 amino acid sequences. All ambiguous positions were removed for each sequence pair. There were a total of 528 positions in the final dataset. Evolutionary analyses were conducted in MEGA6. Source: Courtesy of Nick Knowles.
Figure 2. Picornavirus particle structure. (a) Basic ‘jelly roll’ fold and structures of poliovirus proteins VP1, 2 and 3. (b) The protomeric subunit of the icosahedral capsid showing its orientation with respect to the 5,3,2 symmetry axes. The proteins are colour coded as in (a), with VP4 (a short internal protein) coloured green. (c) Surface representation of the poliovirus capsid (rotated 90° with respect to (b)). The capsid is coloured by radial depth (green innermost through light‐blue to navy outermost) to highlight the most exposed capsid features. A particle twofold axis is shown by a red ellipsoid. (d) Surface representation of the poliovirus receptor (shown in purple/grey) bound to poliovirus (depicted as in (c)). (e) Close‐up of the electron density map (blue) for a twofold region of EV71 (an enterovirus closely related to poliovirus). The proteins are depicted by C‐alpha trace with VP2 in green and VP3 in red. The twofold axis, marked by a red ellipsoid, is straddled by helices from VP2. (f) Close‐up of a twofold of an expanded empty EV71 particle. Conformational changes have led to separation of the twofold helices to open up holes at the twofold and adjacent to the twofold. These holes facilitate the egress of VP4 and the N‐terminus of VP1 from the particle interior. Both are candidates for membrane association and channel formation to transfer of viral genome (which may also exit here) to the cell cytoplasm. (g) Close‐up of an electron density map (blue) showing a twofold axis of an uncoating intermediate of the enterovirus CAV16 (C‐alpha traces are used to depict VP2 (green), VP3 (red)). The N‐terminus of VP1 (drawn in magenta and labelled VP1) has been captured traversing from the particle interior to exit through the hole adjacent to the twofold (as shown in (f)). Source: (a)–(d) Courtesy of Jim Hogle and Mike Strauss. (e)–(g). Courtesy of Liz Fry and Jingshan Ren.
Figure 3. Genome structure and polyprotein processing of viruses of representative genera of the Picornaviridae.
Figure 4. Receptor proteins used by different picornaviruses. CAR, Coxsackie/adenovirus receptor; PVR, poliovirus receptor; ICAM‐1, intercellular adhesion molecule 1; VCAM‐1, vitronectin cellular adhesion molecule 1; DAF, decay‐accelerating factor; HAVcr‐1, hepatitis A virus receptor 1; LDLR, low‐density lipid receptor; α2β1, integrin; αvβ3, integrin; SCARB2, scavenger receptor class B2; CBV, Coxsackie B virus; PV, poliovirus; HRV, human rhinovirus; EMCV, encephalomyocarditis virus; HAV, hepatitis A virus; EV1, echovirus 1; FMDV, foot‐and‐mouth disease virus and CAV9, Coxsackie virus 9. Source: Courtesy of Dr D Evans and Liz Fry.
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Further Reading

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Mahy BWJ (ed.) (2005) Foot‐and‐mouth disease virus. Current Topics in Microbiology and Immunology, vol. 288. Berlin, Heidelberg: Springer. Picornavirus Homepage. http://picornastudygroup.com

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Rowlands DJ (ed) (2003) Foot‐and‐Mouth Disease. Virus Research, vol. 91.

Sobrino F and Domingo E (eds) (2004) Foot‐and‐Mouth Disease: Current Perspectives. Wymondham, Norfolk: Horizon Bioscience.

Zuckerman AJ, Banatvala JE and Pattison JR (eds) (2000) Principles and Practice of Clinical Virology, 4th edn. Chichester, UK: Wiley.

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Rowlands, David J(Sep 2015) Picornaviruses. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001080.pub3]