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A single mutation (V64G) within the RING Domain of Z attenuates Junin virus
Junin virus (JUNV) is a New World arenavirus that is the causative agent of Argentine hemorrhagic fever (AHF). Candid#1 (Can) is a live-attenuated vaccine strain of JUNV that since its introduction has resulted in a marked decrease in AHF incidence within the endemic regions of the Pampas in Argenti...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540883/ https://www.ncbi.nlm.nih.gov/pubmed/32976538 http://dx.doi.org/10.1371/journal.pntd.0008555 |
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author | Hallam, Steven J. Manning, John T. Maruyama, Junki Seregin, Alexey Huang, Cheng Walker, David H. de la Torre, Juan Carlos Paessler, Slobodan |
author_facet | Hallam, Steven J. Manning, John T. Maruyama, Junki Seregin, Alexey Huang, Cheng Walker, David H. de la Torre, Juan Carlos Paessler, Slobodan |
author_sort | Hallam, Steven J. |
collection | PubMed |
description | Junin virus (JUNV) is a New World arenavirus that is the causative agent of Argentine hemorrhagic fever (AHF). Candid#1 (Can) is a live-attenuated vaccine strain of JUNV that since its introduction has resulted in a marked decrease in AHF incidence within the endemic regions of the Pampas in Argentina. Originally, the viral determinants and mechanisms of Can attenuation were not well understood. Recent work has identified the glycoprotein as the major attenuating factor for Can. The establishment of attenuating strategies based on any of the other viral proteins, however, has not been pursued. Here, we document the role of Can Z resulting in incompatibilities with wild type JUNV that results in decreased growth in vitro. In addition, this incompatibility results in attenuation of the virus in the guinea pig model. Further, we identify a single mutation (V64G) in the Z protein that is able to confer this demonstrated attenuation. By establishing and characterizing a novel attenuation strategy for New World mammarenaviruses, we hope to aid future vaccine development for related emerging pathogens including Machupo virus (MACV), Guanarito virus (GTOV), and Sabia virus (SABV). |
format | Online Article Text |
id | pubmed-7540883 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-75408832020-10-19 A single mutation (V64G) within the RING Domain of Z attenuates Junin virus Hallam, Steven J. Manning, John T. Maruyama, Junki Seregin, Alexey Huang, Cheng Walker, David H. de la Torre, Juan Carlos Paessler, Slobodan PLoS Negl Trop Dis Research Article Junin virus (JUNV) is a New World arenavirus that is the causative agent of Argentine hemorrhagic fever (AHF). Candid#1 (Can) is a live-attenuated vaccine strain of JUNV that since its introduction has resulted in a marked decrease in AHF incidence within the endemic regions of the Pampas in Argentina. Originally, the viral determinants and mechanisms of Can attenuation were not well understood. Recent work has identified the glycoprotein as the major attenuating factor for Can. The establishment of attenuating strategies based on any of the other viral proteins, however, has not been pursued. Here, we document the role of Can Z resulting in incompatibilities with wild type JUNV that results in decreased growth in vitro. In addition, this incompatibility results in attenuation of the virus in the guinea pig model. Further, we identify a single mutation (V64G) in the Z protein that is able to confer this demonstrated attenuation. By establishing and characterizing a novel attenuation strategy for New World mammarenaviruses, we hope to aid future vaccine development for related emerging pathogens including Machupo virus (MACV), Guanarito virus (GTOV), and Sabia virus (SABV). Public Library of Science 2020-09-25 /pmc/articles/PMC7540883/ /pubmed/32976538 http://dx.doi.org/10.1371/journal.pntd.0008555 Text en © 2020 Hallam 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 Hallam, Steven J. Manning, John T. Maruyama, Junki Seregin, Alexey Huang, Cheng Walker, David H. de la Torre, Juan Carlos Paessler, Slobodan A single mutation (V64G) within the RING Domain of Z attenuates Junin virus |
title | A single mutation (V64G) within the RING Domain of Z attenuates Junin virus |
title_full | A single mutation (V64G) within the RING Domain of Z attenuates Junin virus |
title_fullStr | A single mutation (V64G) within the RING Domain of Z attenuates Junin virus |
title_full_unstemmed | A single mutation (V64G) within the RING Domain of Z attenuates Junin virus |
title_short | A single mutation (V64G) within the RING Domain of Z attenuates Junin virus |
title_sort | single mutation (v64g) within the ring domain of z attenuates junin virus |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540883/ https://www.ncbi.nlm.nih.gov/pubmed/32976538 http://dx.doi.org/10.1371/journal.pntd.0008555 |
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