Punch, EK, Hover, S orcid.org/0000-0001-9190-5670, Blest, HTW et al. (5 more authors) (2018) Potassium is a trigger for conformational change in the fusion spike of an enveloped RNA virus. Journal of Biological Chemistry, 293 (26). pp. 9937-9944. ISSN 0021-9258
Abstract
Many enveloped viruses enter cells through the endocytic network, from which they must subsequently escape through fusion of viral and endosomal membranes. This membrane fusion is mediated by virus-encoded spikes that respond to the dynamic endosomal environment, which triggers conformational changes in the spikes that initiate the fusion process. Several fusion triggers have been identified and include pH, membrane composition, and endosome-resident proteins, and these cues dictate when and where viral fusion occurs. We recently reported that infection with an enveloped bunyavirus requires elevated potassium ion concentrations [K⁺], controlled by cellular K⁺ channels, that are encountered during viral transit through maturing endosomes. Here we reveal the molecular basis for the K⁺ requirement of bunyaviruses through the first direct visualization of a member of the Nairoviridae family, namely Hazara virus (HAZV), using cryo-EM. Using cryo-electron tomography, we observed HAZV spike glycoproteins within infectious HAZV particles exposed to both high and low [K⁺], which showed that exposure to K⁺ alone results in dramatic changes to the ultrastructural architecture of the virion surface. In low [K⁺], the spikes adopted a compact conformation arranged in locally ordered arrays, whereas, following exposure to high [K⁺], the spikes became extended, and spike–membrane interactions were observed. Viruses exposed to high [K⁺] also displayed enhanced infectivity, thus identifying K⁺ as a newly defined trigger that helps promote viral infection. Finally, we confirmed that K⁺ channel blockers are inhibitory to HAZV infection, highlighting the potential of K⁺ channels as anti-bunyavirus targets.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018 Punch et al. This is an open access article under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
Keywords: | virus entry; fusion protein; electron tomography; conformational change; potassium transport; ion channel; virus structure |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 21 May 2018 15:17 |
Last Modified: | 04 Aug 2018 18:08 |
Status: | Published |
Publisher: | American Society for Biochemistry and Molecular Biology |
Identification Number: | 10.1074/jbc.ra118.002494 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:131043 |