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Neutralization of Junín virus by single domain antibodies targeted against the nucleoprotein
The syndrome viral haemorrhagic fever (VHF) designates a broad range of diseases that are caused by different viruses including members of the family Arenaviridae. Prophylaxis for Argentine Haemorrhagic Fever (AHF), caused by the arenavirus Junín (JUNV), has been achieved by the use of a live attenu...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065417/ https://www.ncbi.nlm.nih.gov/pubmed/30061671 http://dx.doi.org/10.1038/s41598-018-29508-1 |
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author | Linero, Florencia Sepúlveda, Claudia Christopoulou, Ioanna Hulpiau, Paco Scolaro, Luis Saelens, Xavier |
author_facet | Linero, Florencia Sepúlveda, Claudia Christopoulou, Ioanna Hulpiau, Paco Scolaro, Luis Saelens, Xavier |
author_sort | Linero, Florencia |
collection | PubMed |
description | The syndrome viral haemorrhagic fever (VHF) designates a broad range of diseases that are caused by different viruses including members of the family Arenaviridae. Prophylaxis for Argentine Haemorrhagic Fever (AHF), caused by the arenavirus Junín (JUNV), has been achieved by the use of a live attenuated vaccine, named Candid#1. The standard treatment of AHF is transfusion of convalescent human plasma. Our aim was to develop an alternative and safer treatment for AHF based on the use of virus-neutralizing single domain antibodies (VHHs). We describe the first reported VHHs directed against an arenavirus. These VHHs could neutralize Candid#1 by altering virion binding/fusion. Surprisingly, the neutralizing VHHs appeared to be specific for the viral nucleoprotein (N) that is not known to be involved in arenavirus entry. Candid#1 VHH-escape viruses had acquired a predicted N-glycosylation site in the surface glycoprotein GP1 that is present in highly pathogenic JUNV strains. Accordingly, the Candid#1-neutralizing VHHs could not neutralize pathogenic JUNV strains, but they could still bind to cells infected with a pathogenic strain or the escape mutant viruses. These results show that the attenuated strains of JUNV can be potently neutralized by nucleoprotein-specific VHHs. |
format | Online Article Text |
id | pubmed-6065417 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-60654172018-08-06 Neutralization of Junín virus by single domain antibodies targeted against the nucleoprotein Linero, Florencia Sepúlveda, Claudia Christopoulou, Ioanna Hulpiau, Paco Scolaro, Luis Saelens, Xavier Sci Rep Article The syndrome viral haemorrhagic fever (VHF) designates a broad range of diseases that are caused by different viruses including members of the family Arenaviridae. Prophylaxis for Argentine Haemorrhagic Fever (AHF), caused by the arenavirus Junín (JUNV), has been achieved by the use of a live attenuated vaccine, named Candid#1. The standard treatment of AHF is transfusion of convalescent human plasma. Our aim was to develop an alternative and safer treatment for AHF based on the use of virus-neutralizing single domain antibodies (VHHs). We describe the first reported VHHs directed against an arenavirus. These VHHs could neutralize Candid#1 by altering virion binding/fusion. Surprisingly, the neutralizing VHHs appeared to be specific for the viral nucleoprotein (N) that is not known to be involved in arenavirus entry. Candid#1 VHH-escape viruses had acquired a predicted N-glycosylation site in the surface glycoprotein GP1 that is present in highly pathogenic JUNV strains. Accordingly, the Candid#1-neutralizing VHHs could not neutralize pathogenic JUNV strains, but they could still bind to cells infected with a pathogenic strain or the escape mutant viruses. These results show that the attenuated strains of JUNV can be potently neutralized by nucleoprotein-specific VHHs. Nature Publishing Group UK 2018-07-30 /pmc/articles/PMC6065417/ /pubmed/30061671 http://dx.doi.org/10.1038/s41598-018-29508-1 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Linero, Florencia Sepúlveda, Claudia Christopoulou, Ioanna Hulpiau, Paco Scolaro, Luis Saelens, Xavier Neutralization of Junín virus by single domain antibodies targeted against the nucleoprotein |
title | Neutralization of Junín virus by single domain antibodies targeted against the nucleoprotein |
title_full | Neutralization of Junín virus by single domain antibodies targeted against the nucleoprotein |
title_fullStr | Neutralization of Junín virus by single domain antibodies targeted against the nucleoprotein |
title_full_unstemmed | Neutralization of Junín virus by single domain antibodies targeted against the nucleoprotein |
title_short | Neutralization of Junín virus by single domain antibodies targeted against the nucleoprotein |
title_sort | neutralization of junín virus by single domain antibodies targeted against the nucleoprotein |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065417/ https://www.ncbi.nlm.nih.gov/pubmed/30061671 http://dx.doi.org/10.1038/s41598-018-29508-1 |
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