The cryo-EM structure of vesivirus 2117 highlights functional variations in entry pathways for viruses in different clades of the vesivirus genus

Sutherland, H., Conley, M. J. , Emmott, E., Streetley, J. , Goodfellow, I. G. and Bhella, D. (2021) The cryo-EM structure of vesivirus 2117 highlights functional variations in entry pathways for viruses in different clades of the vesivirus genus. Journal of Virology, 95(13), e0028221. (doi: 10.1128/JVI.00282-21) (PMID:33853966)

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Vesivirus 2117 is an adventitious agent that has been responsible for lost productivity in biopharmaceutical production following contamination of Chinese hamster ovary cell cultures in commercial bioreactors. A member of the Caliciviridae, 2117 is classified within the Vesivirus genus in a clade that includes canine and mink caliciviruses but is distinct from the vesicular exanthema of swine clade, which includes the extensively studied feline calicivirus (FCV). We have used cryogenic electron microscopy (cryo-EM) to determine the structure of the capsid of this small, icosahedral, positive-sense RNA containing virus. We show that the outer face of the dimeric capsomeres, which contains the receptor binding site and major immunodominant epitopes in all caliciviruses studied thus far, is quite different from that of FCV. This is a consequence of a 22 amino-acid insertion in the sequence of the FCV major capsid protein that forms a ‘cantilevered arm’, which plays an important role in both receptor engagement and undergoes structural rearrangements thought to be important for genome delivery to the cytosol. Our data highlight a potentially important difference in the attachment and entry pathways employed by the different clades of the Vesivirus genus.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Conley, Dr Michaela and Bhella, Professor David and Goodfellow, Professor Ian and Streetley, Dr James
Authors: Sutherland, H., Conley, M. J., Emmott, E., Streetley, J., Goodfellow, I. G., and Bhella, D.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Journal of Virology
Publisher:American Society for Microbiology
ISSN (Online):1098-5514
Published Online:14 April 2021
Copyright Holders:Copyright © 2021 American Society for Microbiology
First Published:First published in Journal of Virology 95(13): e0028221
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
301445The Scottish Macromolecular Imaging Centre (SMIC)David BhellaMedical Research Council (MRC)MC_PC_17135III - Centre for Virus Research
301474The purchase and maintenance of a cryo-electron microscopeDavid BhellaScottish Funding Council (SFC)H17007III - Centre for Virus Research
656541Structural studies of human viruses and host interactionsDavid BhellaMedical Research Council (MRC)MC_UU_12014/7MVLS III - CENTRE FOR VIRUS RESEARCH
306358Host and viral factors in the emergence of a virulent strain of calicivirusMargaret HosieBiotechnology and Biological Sciences Research Council (BBSRC)BB/T002239/1III - Centre for Virus Research