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Evaluation and use of in-silico structure-based epitope prediction with foot-and-mouth disease virus

DOI: 10.1371/journal.pone.0061122 DOI Help
PMID: 23667434 PMID Help

Authors: Daryl W. Borley (The Pirbright Institute; University of Oxford) , Mana Mahapatra (The Pirbright Institute) , David J. Paton (The Pirbright Institute) , Robert Esnouf (University of Oxford) , David I. Stuart (University of Oxford; Diamond Light Source) , Elizabeth E. Fry (University of Oxford)
Co-authored by industrial partner: Yes

Type: Journal Paper
Journal: Plos One , VOL 8 (5)

State: Published (Approved)
Published: May 2013

Open Access Open Access

Abstract: Understanding virus antigenicity is of fundamental importance for the development of better, more cross-reactive vaccines. However, as far as we are aware, no systematic work has yet been conducted using the 3D structure of a virus to identify novel epitopes. Therefore we have extended several existing structural prediction algorithms to build a method for identifying epitopes on the appropriate outer surface of intact virus capsids (which are structurally different from globular proteins in both shape and arrangement of multiple repeated elements) and applied it here as a proof of principle concept to the capsid of foot-and-mouth disease virus (FMDV). We have analysed how reliably several freely available structure-based B cell epitope prediction programs can identify already known viral epitopes of FMDV in the context of the viral capsid. To do this we constructed a simple objective metric to measure the sensitivity and discrimination of such algorithms. After optimising the parameters for five methods using an independent training set we used this measure to evaluate the methods. Individually any one algorithm performed rather poorly (three performing better than the other two) suggesting that there may be value in developing virus-specific software. Taking a very conservative approach requiring a consensus between all three top methods predicts a number of previously described antigenic residues as potential epitopes on more than one serotype of FMDV, consistent with experimental results. The consensus results identified novel residues as potential epitopes on more than one serotype. These include residues 190–192 of VP2 (not previously determined to be antigenic), residues 69–71 and 193–197 of VP3 spanning the pentamer-pentamer interface, and another region incorporating residues 83, 84 and 169–174 of VP1 (all only previously experimentally defined on serotype A). The computer programs needed to create a semi-automated procedure for carrying out this epitope prediction method are presented.

Journal Keywords: Capsids; Viral structure; Foot and mouth disease; Computer software; Antigens; Rhinovirus; Poliovirus; Algorithms

Diamond Keywords: Foot-and-Mouth Disease (FMD); Viruses

Subject Areas: Biology and Bio-materials, Medicine, Information and Communication Technology


Technical Areas: Diagnostics

Added On: 15/05/2013 09:00

Documents:
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Discipline Tags:

Pathogens Health & Wellbeing Agriculture & Fisheries Computing & software technologies Information & Communication Technologies Structural biology Life Sciences & Biotech Veterinary Medicine

Technical Tags:

Diffraction Macromolecular Crystallography (MX)