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Structures of foot and mouth disease virus pentamers: Insight into capsid dissociation and unexpected pentamer reassociation

DOI: 10.1371/journal.ppat.1006607 DOI Help

Authors: Nayab Malik (University of Oxford) , Abhay Kotecha (University of Oxford) , Sarah Gold (The Pirbright Institute) , Amin Asfor (The Pirbright Institute) , Jingshan Ren (University of Oxford) , Juha T. Huiskonen (University of Oxford) , Tobias J. Tuthill (The Pirbright Institute) , Elizabeth E. Fry (University of Oxford) , David I. Stuart (University of Oxford; Diamond Light Source)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Plos Pathogens , VOL 13

State: Published (Approved)
Published: September 2017

Open Access Open Access

Abstract: Foot-and-mouth disease virus (FMDV) belongs to the aphthovirus genus of the Picornaviridae, a family of small, icosahedral, non-enveloped, single-stranded RNA viruses. It is a highly infectious pathogen and is one of the biggest hindrances to the international trade of animals and animal products. FMDV capsids (which are unstable below pH6.5) release their genome into the host cell from an acidic compartment, such as that of an endosome, and in the process dissociate into pentamers. Whilst other members of the family (enteroviruses) have been visualized to form an expanded intermediate capsid with holes from which inner capsid proteins (VP4), N-termini (VP1) and RNA can be released, there has been no visualization of any such state for an aphthovirus, instead the capsid appears to simply dissociate into pentamers. Here we present the 8-Å resolution structure of isolated dissociated pentamers of FMDV, lacking VP4. We also found these pentamers to re-associate into a rigid, icosahedrally symmetric assembly, which enabled their structure to be solved at higher resolution (5.2 Å). In this assembly, the pentamers unexpectedly associate ‘inside out’, but still with their exposed hydrophobic edges buried. Stabilizing interactions occur between the HI loop of VP2 and its symmetry related partners at the icosahedral 3-fold axes, and between the BC and EF loops of VP3 with the VP2 βB-strand and the CD loop at the 2-fold axes. A relatively extensive but subtle structural rearrangement towards the periphery of the dissociated pentamer compared to that in the mature virus provides insight into the mechanism of dissociation of FMDV and the marked difference in antigenicity.

Journal Keywords: Viral packaging; Viral structure; Foot and mouth disease; Electron cryo-microscopy; Electron density; Picornaviruses; Sucrose; Virions

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

Subject Areas: Biology and Bio-materials

Diamond Offline Facilities: Electron Bio-Imaging Centre (eBIC)
Instruments: M01-Polara at OPIC (Oxford)

Added On: 26/09/2017 13:50

Discipline Tags:

Pathogens Infectious Diseases Health & Wellbeing Structural biology Life Sciences & Biotech Veterinary Medicine

Technical Tags:

Microscopy Electron Microscopy (EM) Cryo Electron Microscopy (Cryo EM)