Bunyavirus requirement for endosomal K+ reveals new roles of cellular ion channels during infection

Hover, S., Foster, B., Fontana, J., Kohl, A. , Goldstein, S. A.N., Barr, J. N. and Mankouri, J. (2018) Bunyavirus requirement for endosomal K+ reveals new roles of cellular ion channels during infection. PLoS Pathogens, 14(1), e1006845. (doi: 10.1371/journal.ppat.1006845) (PMID:29352299) (PMCID:PMC5805358)

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Abstract

In order to multiply and cause disease a virus must transport its genome from outside the cell into the cytosol, most commonly achieved through the endocytic network. Endosomes transport virus particles to specific cellular destinations and viruses exploit the changing environment of maturing endocytic vesicles as triggers to mediate genome release. Previously we demonstrated that several bunyaviruses, which comprise the largest family of negative sense RNA viruses, require the activity of cellular potassium (K+) channels to cause productive infection. Specifically, we demonstrated a surprising role for K+ channels during virus endosomal trafficking. In this study, we have used the prototype bunyavirus, Bunyamwera virus (BUNV), as a tool to understand why K+ channels are required for progression of these viruses through the endocytic network. We report three major findings: First, the production of a dual fluorescently labelled bunyavirus to visualize virus trafficking in live cells. Second, we show that BUNV traffics through endosomes containing high [K+] and that these K+ ions influence the infectivity of virions. Third, we show that K+ channel inhibition can alter the distribution of K+ across the endosomal system and arrest virus trafficking in endosomes. These data suggest high endosomal [K+] is a critical cue that is required for virus infection, and is controlled by cellular K+ channels resident within the endosome network. This highlights cellular K+ channels as druggable targets to impede virus entry, infection and disease.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Kohl, Professor Alain
Creator Roles:
Kohl, A.Conceptualization, Writing – review and editing
Authors: Hover, S., Foster, B., Fontana, J., Kohl, A., Goldstein, S. A.N., Barr, J. N., and Mankouri, J.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:PLoS Pathogens
Publisher:Public Library of Science
ISSN:1553-7366
ISSN (Online):1553-7374
Copyright Holders:Copyright © 2018 Hover et al.
First Published:First published in PLoS Pathogens 14(1):e1006845
Publisher Policy:Reproduced under a Creative Commons License

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