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Assessment of Inhibitors of Pathogenic Crimean-Congo Hemorrhagic Fever Virus Strains Using Virus-Like Particles

Crimean-Congo hemorrhagic fever (CCHF) is an often lethal, acute inflammatory illness that affects a large geographic area. The disease is caused by infection with CCHF virus (CCHFV), a nairovirus from the Bunyaviridae family. Basic research on CCHFV has been severely hampered by biosafety requireme...

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Autores principales: Zivcec, Marko, Metcalfe, Maureen G., Albariño, César G., Guerrero, Lisa W., Pegan, Scott D., Spiropoulou, Christina F., Bergeron, Éric
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4666410/
https://www.ncbi.nlm.nih.gov/pubmed/26625182
http://dx.doi.org/10.1371/journal.pntd.0004259
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author Zivcec, Marko
Metcalfe, Maureen G.
Albariño, César G.
Guerrero, Lisa W.
Pegan, Scott D.
Spiropoulou, Christina F.
Bergeron, Éric
author_facet Zivcec, Marko
Metcalfe, Maureen G.
Albariño, César G.
Guerrero, Lisa W.
Pegan, Scott D.
Spiropoulou, Christina F.
Bergeron, Éric
author_sort Zivcec, Marko
collection PubMed
description Crimean-Congo hemorrhagic fever (CCHF) is an often lethal, acute inflammatory illness that affects a large geographic area. The disease is caused by infection with CCHF virus (CCHFV), a nairovirus from the Bunyaviridae family. Basic research on CCHFV has been severely hampered by biosafety requirements and lack of available strains and molecular tools. We report the development of a CCHF transcription- and entry-competent virus-like particle (tecVLP) system that can be used to study cell entry and viral transcription/replication over a broad dynamic range (~4 orders of magnitude). The tecVLPs are morphologically similar to authentic CCHFV. Incubation of immortalized and primary human cells with tecVLPs results in a strong reporter signal that is sensitive to treatment with neutralizing monoclonal antibodies and by small molecule inhibitors of CCHFV. We used glycoproteins and minigenomes from divergent CCHFV strains to generate tecVLPs, and in doing so, we identified a monoclonal antibody that can prevent cell entry of tecVLPs containing glycoproteins from 3 pathogenic CCHFV strains. In addition, our data suggest that different glycoprotein moieties confer different cellular entry efficiencies, and that glycoproteins from the commonly used strain IbAr10200 have up to 100-fold lower ability to enter primary human cells compared to glycoproteins from pathogenic CCHFV strains.
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spelling pubmed-46664102015-12-10 Assessment of Inhibitors of Pathogenic Crimean-Congo Hemorrhagic Fever Virus Strains Using Virus-Like Particles Zivcec, Marko Metcalfe, Maureen G. Albariño, César G. Guerrero, Lisa W. Pegan, Scott D. Spiropoulou, Christina F. Bergeron, Éric PLoS Negl Trop Dis Research Article Crimean-Congo hemorrhagic fever (CCHF) is an often lethal, acute inflammatory illness that affects a large geographic area. The disease is caused by infection with CCHF virus (CCHFV), a nairovirus from the Bunyaviridae family. Basic research on CCHFV has been severely hampered by biosafety requirements and lack of available strains and molecular tools. We report the development of a CCHF transcription- and entry-competent virus-like particle (tecVLP) system that can be used to study cell entry and viral transcription/replication over a broad dynamic range (~4 orders of magnitude). The tecVLPs are morphologically similar to authentic CCHFV. Incubation of immortalized and primary human cells with tecVLPs results in a strong reporter signal that is sensitive to treatment with neutralizing monoclonal antibodies and by small molecule inhibitors of CCHFV. We used glycoproteins and minigenomes from divergent CCHFV strains to generate tecVLPs, and in doing so, we identified a monoclonal antibody that can prevent cell entry of tecVLPs containing glycoproteins from 3 pathogenic CCHFV strains. In addition, our data suggest that different glycoprotein moieties confer different cellular entry efficiencies, and that glycoproteins from the commonly used strain IbAr10200 have up to 100-fold lower ability to enter primary human cells compared to glycoproteins from pathogenic CCHFV strains. Public Library of Science 2015-12-01 /pmc/articles/PMC4666410/ /pubmed/26625182 http://dx.doi.org/10.1371/journal.pntd.0004259 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Zivcec, Marko
Metcalfe, Maureen G.
Albariño, César G.
Guerrero, Lisa W.
Pegan, Scott D.
Spiropoulou, Christina F.
Bergeron, Éric
Assessment of Inhibitors of Pathogenic Crimean-Congo Hemorrhagic Fever Virus Strains Using Virus-Like Particles
title Assessment of Inhibitors of Pathogenic Crimean-Congo Hemorrhagic Fever Virus Strains Using Virus-Like Particles
title_full Assessment of Inhibitors of Pathogenic Crimean-Congo Hemorrhagic Fever Virus Strains Using Virus-Like Particles
title_fullStr Assessment of Inhibitors of Pathogenic Crimean-Congo Hemorrhagic Fever Virus Strains Using Virus-Like Particles
title_full_unstemmed Assessment of Inhibitors of Pathogenic Crimean-Congo Hemorrhagic Fever Virus Strains Using Virus-Like Particles
title_short Assessment of Inhibitors of Pathogenic Crimean-Congo Hemorrhagic Fever Virus Strains Using Virus-Like Particles
title_sort assessment of inhibitors of pathogenic crimean-congo hemorrhagic fever virus strains using virus-like particles
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4666410/
https://www.ncbi.nlm.nih.gov/pubmed/26625182
http://dx.doi.org/10.1371/journal.pntd.0004259
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