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Bunyavirus requirement for endosomal K(+) reveals new roles of cellular ion channels during infection
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 endocy...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805358/ https://www.ncbi.nlm.nih.gov/pubmed/29352299 http://dx.doi.org/10.1371/journal.ppat.1006845 |
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author | Hover, Samantha Foster, Becky Fontana, Juan Kohl, Alain Goldstein, Steve A. N. Barr, John N. Mankouri, Jamel |
author_facet | Hover, Samantha Foster, Becky Fontana, Juan Kohl, Alain Goldstein, Steve A. N. Barr, John N. Mankouri, Jamel |
author_sort | Hover, Samantha |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5805358 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-58053582018-02-23 Bunyavirus requirement for endosomal K(+) reveals new roles of cellular ion channels during infection Hover, Samantha Foster, Becky Fontana, Juan Kohl, Alain Goldstein, Steve A. N. Barr, John N. Mankouri, Jamel PLoS Pathog Research Article 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. Public Library of Science 2018-01-19 /pmc/articles/PMC5805358/ /pubmed/29352299 http://dx.doi.org/10.1371/journal.ppat.1006845 Text en © 2018 Hover et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Hover, Samantha Foster, Becky Fontana, Juan Kohl, Alain Goldstein, Steve A. N. Barr, John N. Mankouri, Jamel Bunyavirus requirement for endosomal K(+) reveals new roles of cellular ion channels during infection |
title | Bunyavirus requirement for endosomal K(+) reveals new roles of cellular ion channels during infection |
title_full | Bunyavirus requirement for endosomal K(+) reveals new roles of cellular ion channels during infection |
title_fullStr | Bunyavirus requirement for endosomal K(+) reveals new roles of cellular ion channels during infection |
title_full_unstemmed | Bunyavirus requirement for endosomal K(+) reveals new roles of cellular ion channels during infection |
title_short | Bunyavirus requirement for endosomal K(+) reveals new roles of cellular ion channels during infection |
title_sort | bunyavirus requirement for endosomal k(+) reveals new roles of cellular ion channels during infection |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805358/ https://www.ncbi.nlm.nih.gov/pubmed/29352299 http://dx.doi.org/10.1371/journal.ppat.1006845 |
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