Equine Rhinitis A Virus and Its Low pH Empty Particle: Clues Towards an Aphthovirus Entry Mechanism?

DOI: 10.1371/journal.ppat.1000620
PMID: 19816570

Authors: Tobias Tuthill (University of Leeds) , Karl Harlos (Wellcome Trust Centre for Human Genetics, University of Oxford) , Thomas Walter (University of Oxford) , Nick J. Knowles (Institute for Animal Health, Pirbright Laboratory) , Elisabetta Groppelli (University of Leeds) , David J. Rowlands (University of Leeds) , David I. Stuart (University of Oxford) , Liz Fry (University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Plos Pathogens , VOL 5 (10)

State: Published (Approved)
Published: October 2009

Abstract: Picornaviruses are small animal viruses comprising an RNA genome protected by a roughly spherical protein shell with icosahedral symmetry. How the RNA is introduced into the cytoplasm of the host cell to initiate replication is unclear since they have no lipid envelope to facilitate fusion with cellular membranes. Instead, they become internalized into endocytic vesicles whence the viral genome must be delivered through the vesicle membrane, into the cytoplasm. In some picornaviruses (enteroviruses), genome delivery is proposed to be coordinated by an intact particle inducing pore formation in the membrane through which the genome can be transferred directly without exposure to the hostile vesicle environment. In contrast, other picornaviruses (aphthoviruses e.g. ERAV, FMDV) present a dilemma by appearing to simply fall apart in acidified vesicles. Here we show that acid treatment results in the formation of an intact but transient aphthovirus empty particle from which the genome has been released. We have determined the crystal structures of the ERAV particle at native and acidic pH. The acid induced structure is consistent with a destabilized particle en-route to disassembly. We propose that the entry process for this group of viruses involves externalisation of the RNA from a novel capsid intermediate and unifies in principle the entry process for all picornaviruses.

Subject Areas: Biology and Bio-materials

Facility: ESRF