Time filter

Source Type

Didcot, United Kingdom

Zhu L.,University of Oxford | Zhu L.,Pirbright Institute | Wang X.,CAS Institute of Biophysics | Ren J.,University of Oxford | And 14 more authors.
Nature Communications | Year: 2015

Picornaviruses are responsible for a range of human and animal diseases, but how their RNA genome is packaged remains poorly understood. A particularly poorly studied group within this family are those that lack the internal coat protein, VP4. Here we report the atomic structure of one such virus, Ljungan virus, the type member of the genus Parechovirus B, which has been linked to diabetes and myocarditis in humans. The 3.78-Å resolution cryo-electron microscopy structure shows remarkable features, including an extended VP1 C terminus, forming a major protuberance on the outer surface of the virus, and a basic motif at the N terminus of VP3, binding to which orders some 12% of the viral genome. This apparently charge-driven RNA attachment suggests that this branch of the picornaviruses uses a different mechanism of genome encapsidation, perhaps explored early in the evolution of picornaviruses. © 2015 Macmillan Publishers Limited. All rights reserved.

Wang X.,CAS Institute of Biophysics | Peng W.,CAS Institute of Biophysics | Ren J.,University of Oxford | Hu Z.,National Institutes for Food and Drug Control | And 16 more authors.
Nature Structural and Molecular Biology | Year: 2012

Enterovirus 71 (EV71) is a major agent of hand, foot and mouth disease in children that can cause severe central nervous system disease and death. No vaccine or antiviral therapy is available. High-resolution structural analysis of the mature virus and natural empty particles shows that the mature virus is structurally similar to other enteroviruses. In contrast, the empty particles are markedly expanded and resemble elusive enterovirus-uncoating intermediates not previously characterized in atomic detail. Hydrophobic pockets in the EV71 capsid are collapsed in this expanded particle, providing a detailed explanation of the mechanism for receptor-binding triggered virus uncoating. These structures provide a model for enterovirus uncoating in which the VP1 GH loop acts as an adaptor-sensor for cellular receptor attachment, converting heterologous inputs to a generic uncoating mechanism, highlighting new opportunities for therapeutic intervention. © 2012 Nature America, Inc. All rights reserved.

Ren J.,University of Oxford | Wang X.,CAS Institute of Biophysics | Hu Z.,National Institutes for Food and Drug Control | Gao Q.,Sinovac Biotech | And 17 more authors.
Nature Communications | Year: 2013

It remains largely mysterious how the genomes of non-enveloped eukaryotic viruses are transferred across a membrane into the host cell. Picornaviruses are simple models for such viruses, and initiate this uncoating process through particle expansion, which reveals channels through which internal capsid proteins and the viral genome presumably exit the particle, although this has not been clearly seen until now. Here we present the atomic structure of an uncoating intermediate for the major human picornavirus pathogen CAV16, which reveals VP1 partly extruded from the capsid, poised to embed in the host membrane. Together with previous low-resolution results, we are able to propose a detailed hypothesis for the ordered egress of the internal proteins, using two distinct sets of channels through the capsid, and suggest a structural link to the condensed RNA within the particle, which may be involved in triggering RNA release. ©; 2013 Macmillan Publishers Limited. All rights reserved.

Discover hidden collaborations