Structure of a phleboviral envelope glycoprotein reveals a consolidated model of membrane fusion.

Halldorsson, S., Behrens, A.-J., Harlos, K., Huiskonen, J. T., Elliott, R. M., Crispin, M., Brennan, B. and Bowden, T. A. (2016) Structure of a phleboviral envelope glycoprotein reveals a consolidated model of membrane fusion. Proceedings of the National Academy of Sciences of the United States of America, 113(26), pp. 7145-7159. (doi:10.1073/pnas.1603827113) (PMID:27325770) (PMCID:PMC4932967)

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Abstract

An emergent viral pathogen termed severe fever with thrombocytopenia syndrome virus (SFTSV) is responsible for thousands of clinical cases and associated fatalities in China, Japan, and South Korea. Akin to other phleboviruses, SFTSV relies on a viral glycoprotein, Gc, to catalyze the merger of endosomal host and viral membranes during cell entry. Here, we describe the postfusion structure of SFTSV Gc, revealing that the molecular transformations the phleboviral Gc undergoes upon host cell entry are conserved with otherwise unrelated alpha- and flaviviruses. By comparison of SFTSV Gc with that of the prefusion structure of the related Rift Valley fever virus, we show that these changes involve refolding of the protein into a trimeric state. Reverse genetics and rescue of site-directed histidine mutants enabled localization of histidines likely to be important for triggering this pH-dependent process. These data provide structural and functional evidence that the mechanism of phlebovirus-host cell fusion is conserved among genetically and patho-physiologically distinct viral pathogens.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Elliott, Professor Richard and Brennan, Dr Benjamin
Authors: Halldorsson, S., Behrens, A.-J., Harlos, K., Huiskonen, J. T., Elliott, R. M., Crispin, M., Brennan, B., and Bowden, T. A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Academy of Sciences
ISSN:0027-8424
ISSN (Online):1091-6490
Published Online:20 June 2016
Copyright Holders:Copyright © 2016 National Academy of Sciences
First Published:First published in Proceedings of the National Academy of Sciences of the United States of America 113(26): 7145-7159
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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