Calicivirus VP2 forms a portal-like assembly following receptor engagement

Conley, M. J. , McElwee, M., Azmi, L., Gabrielsen, M. , Byron, O. , Goodfellow, I. G. and Bhella, D. (2019) Calicivirus VP2 forms a portal-like assembly following receptor engagement. Nature, 565(7739), pp. 377-381. (doi: 10.1038/s41586-018-0852-1) (PMID:30626974)

175090.pdf - Accepted Version



To initiate infection, many viruses enter their host cells by triggering endocytosis following receptor engagement. However, the mechanisms by which non-enveloped viruses escape the endosome are poorly understood. Here we present near-atomic-resolution cryo-electron microscopy structures for feline calicivirus both undecorated and labelled with a soluble fragment of its cellular receptor, feline junctional adhesion molecule A. We show that VP2, a minor capsid protein encoded by all caliciviruses1,2, forms a large portal-like assembly at a unique three-fold axis of symmetry, following receptor engagement. This assembly—which was not detected in undecorated virions—is formed of twelve copies of VP2, arranged with their hydrophobic N termini pointing away from the virion surface. Local rearrangement at the portal site leads to the opening of a pore in the capsid shell. We hypothesize that the portal-like assembly functions as a channel for the delivery of the calicivirus genome, through the endosomal membrane, into the cytoplasm of a host cell, thereby initiating infection. VP2 was previously known to be critical for the production of infectious virus3; our findings provide insights into its structure and function that advance our understanding of the Caliciviridae.

Item Type:Articles
Additional Information:Also funded by The Wellcome Trust 207498/Z/17/Z.
Glasgow Author(s) Enlighten ID:Gabrielsen, Dr Mads and Conley, Dr Michaela and Bhella, Professor David and McElwee, Dr Marion and Goodfellow, Professor Ian and Byron, Professor Olwyn
Authors: Conley, M. J., McElwee, M., Azmi, L., Gabrielsen, M., Byron, O., Goodfellow, I. G., and Bhella, D.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:Nature
Publisher:Nature Publishing Group
ISSN (Online):1476-4687
Published Online:09 January 2019
Copyright Holders:Copyright © 2019 Springer Nature Limited
First Published:First published in Nature 565(7739): 377-381
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
588759BBSRC Doctoral Training Partnership 2012George BaillieBiotechnology and Biological Sciences Research Council (BBSRC)BB/J013854/1MVLS COLLEGE SENIOR MANAGEMENT
656541Structural studies of human viruses and host interactionsDavid BhellaMedical Research Council (MRC)MC_UU_12014/7MVLS III - CENTRE FOR VIRUS RESEARCH