Differential pathogenesis of closely related 2018 Nigerian outbreak clade III Lassa virus isolates.

Nigeria continues to experience ever increasing annual outbreaks of Lassa fever (LF). The World Health Organization has recently declared Lassa virus (LASV) as a priority pathogen for accelerated research leading to a renewed international effort to develop relevant animal models of disease and effe...

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Autores principales:	Derek R Stein, Bryce M Warner, Jonathan Audet, Geoff Soule, Vinayakumar Siragam, Patrycja Sroga, Bryan D Griffin, Anders Leung, Allen Grolla, Kevin Tierney, Alix Albietz, Darwyn Kobasa, Abdulmajid S Musa, Adama Ahmad, Afolabi M Akinpelu, Nwando Mba, Rebecca Rosenke, Dana P Scott, Greg Saturday, Chikwe Ihekweazu, David Safronetz
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/9f82772fd3584798b0bfe017968a7c73
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spelling	oai:doaj.org-article:9f82772fd3584798b0bfe017968a7c732021-12-02T20:00:03ZDifferential pathogenesis of closely related 2018 Nigerian outbreak clade III Lassa virus isolates.1553-73661553-737410.1371/journal.ppat.1009966https://doaj.org/article/9f82772fd3584798b0bfe017968a7c732021-10-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009966https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Nigeria continues to experience ever increasing annual outbreaks of Lassa fever (LF). The World Health Organization has recently declared Lassa virus (LASV) as a priority pathogen for accelerated research leading to a renewed international effort to develop relevant animal models of disease and effective countermeasures to reduce LF morbidity and mortality in endemic West African countries. A limiting factor in evaluating medical countermeasures against LF is a lack of well characterized animal models outside of those based on infection with LASV strain Josiah originating form Sierra Leone, circa 1976. Here we genetically characterize five recent LASV isolates collected from the 2018 outbreak in Nigeria. Three isolates were further evaluated in vivo and despite being closely related and from the same spatial / geographic region of Nigeria, only one of the three isolates proved lethal in strain 13 guinea pigs and non-human primates (NHP). Additionally, this isolate exhibited atypical pathogenesis characteristics in the NHP model, most notably respiratory failure, not commonly described in hemorrhagic cases of LF. These results suggest that there is considerable phenotypic heterogeneity in LASV infections in Nigeria, which leads to a multitude of pathogenesis characteristics that could account for differences between subclinical and lethal LF infections. Most importantly, the development of disease models using currently circulating LASV strains in West Africa are critical for the evaluation of potential vaccines and medical countermeasures.Derek R SteinBryce M WarnerJonathan AudetGeoff SouleVinayakumar SiragamPatrycja SrogaBryan D GriffinAnders LeungAllen GrollaKevin TierneyAlix AlbietzDarwyn KobasaAbdulmajid S MusaAdama AhmadAfolabi M AkinpeluNwando MbaRebecca RosenkeDana P ScottGreg SaturdayChikwe IhekweazuDavid SafronetzPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 10, p e1009966 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Derek R Stein Bryce M Warner Jonathan Audet Geoff Soule Vinayakumar Siragam Patrycja Sroga Bryan D Griffin Anders Leung Allen Grolla Kevin Tierney Alix Albietz Darwyn Kobasa Abdulmajid S Musa Adama Ahmad Afolabi M Akinpelu Nwando Mba Rebecca Rosenke Dana P Scott Greg Saturday Chikwe Ihekweazu David Safronetz Differential pathogenesis of closely related 2018 Nigerian outbreak clade III Lassa virus isolates.
description	Nigeria continues to experience ever increasing annual outbreaks of Lassa fever (LF). The World Health Organization has recently declared Lassa virus (LASV) as a priority pathogen for accelerated research leading to a renewed international effort to develop relevant animal models of disease and effective countermeasures to reduce LF morbidity and mortality in endemic West African countries. A limiting factor in evaluating medical countermeasures against LF is a lack of well characterized animal models outside of those based on infection with LASV strain Josiah originating form Sierra Leone, circa 1976. Here we genetically characterize five recent LASV isolates collected from the 2018 outbreak in Nigeria. Three isolates were further evaluated in vivo and despite being closely related and from the same spatial / geographic region of Nigeria, only one of the three isolates proved lethal in strain 13 guinea pigs and non-human primates (NHP). Additionally, this isolate exhibited atypical pathogenesis characteristics in the NHP model, most notably respiratory failure, not commonly described in hemorrhagic cases of LF. These results suggest that there is considerable phenotypic heterogeneity in LASV infections in Nigeria, which leads to a multitude of pathogenesis characteristics that could account for differences between subclinical and lethal LF infections. Most importantly, the development of disease models using currently circulating LASV strains in West Africa are critical for the evaluation of potential vaccines and medical countermeasures.
format	article
author	Derek R Stein Bryce M Warner Jonathan Audet Geoff Soule Vinayakumar Siragam Patrycja Sroga Bryan D Griffin Anders Leung Allen Grolla Kevin Tierney Alix Albietz Darwyn Kobasa Abdulmajid S Musa Adama Ahmad Afolabi M Akinpelu Nwando Mba Rebecca Rosenke Dana P Scott Greg Saturday Chikwe Ihekweazu David Safronetz
author_facet	Derek R Stein Bryce M Warner Jonathan Audet Geoff Soule Vinayakumar Siragam Patrycja Sroga Bryan D Griffin Anders Leung Allen Grolla Kevin Tierney Alix Albietz Darwyn Kobasa Abdulmajid S Musa Adama Ahmad Afolabi M Akinpelu Nwando Mba Rebecca Rosenke Dana P Scott Greg Saturday Chikwe Ihekweazu David Safronetz
author_sort	Derek R Stein
title	Differential pathogenesis of closely related 2018 Nigerian outbreak clade III Lassa virus isolates.
title_short	Differential pathogenesis of closely related 2018 Nigerian outbreak clade III Lassa virus isolates.
title_full	Differential pathogenesis of closely related 2018 Nigerian outbreak clade III Lassa virus isolates.
title_fullStr	Differential pathogenesis of closely related 2018 Nigerian outbreak clade III Lassa virus isolates.
title_full_unstemmed	Differential pathogenesis of closely related 2018 Nigerian outbreak clade III Lassa virus isolates.
title_sort	differential pathogenesis of closely related 2018 nigerian outbreak clade iii lassa virus isolates.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/9f82772fd3584798b0bfe017968a7c73
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Differential pathogenesis of closely related 2018 Nigerian outbreak clade III Lassa virus isolates.

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