Lethal Infection of Lassa Virus Isolated from a Human Clinical Sample in Outbred Guinea Pigs without Adaptation

ABSTRACT Lassa virus (LASV), a member of the family Arenaviridae, is the causative agent of Lassa fever. Lassa virus is endemic in West African countries, such as Nigeria, Guinea, Liberia, and Sierra Leone, and causes outbreaks annually. Lassa fever onset begins with “flu-like” symptoms and may deve...

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Autores principales:	Junki Maruyama, John T. Manning, Elizabeth J. Mateer, Rachel Sattler, Natalya Bukreyeva, Cheng Huang, Slobodan Paessler
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Lassa virus guinea pig animal model clinical isolate Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/8da41667acbb4114929cd424d03417fa
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spelling	oai:doaj.org-article:8da41667acbb4114929cd424d03417fa2021-11-15T15:27:33ZLethal Infection of Lassa Virus Isolated from a Human Clinical Sample in Outbred Guinea Pigs without Adaptation10.1128/mSphere.00428-192379-5042https://doaj.org/article/8da41667acbb4114929cd424d03417fa2019-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00428-19https://doaj.org/toc/2379-5042ABSTRACT Lassa virus (LASV), a member of the family Arenaviridae, is the causative agent of Lassa fever. Lassa virus is endemic in West African countries, such as Nigeria, Guinea, Liberia, and Sierra Leone, and causes outbreaks annually. Lassa fever onset begins with “flu-like” symptoms and may develop into lethal hemorrhagic disease in severe cases. Although Lassa virus is one of the most alarming pathogens from a public health perspective, there are few licensed vaccines or therapeutics against Lassa fever. The fact that animal models are limited and the fact that mostly laboratory-derived viruses are used for studies limit the successful development of countermeasures. In this study, we demonstrated that the LASV isolate LF2384-NS-DIA-1 (LF2384), which was directly isolated from a serum sample from a fatal human Lassa fever case in the 2012 Sierra Leone outbreak, causes uniformly lethal infection in outbred Hartley guinea pigs without virus-host adaptation. This is the first report of a clinically isolated strain of LASV causing lethal infection in outbred guinea pigs. This novel guinea pig model of Lassa fever may contribute to Lassa fever research and the development of vaccines and therapeutics. IMPORTANCE Lassa virus, the causative agent of Lassa fever, is a zoonotic pathogen causing annual outbreaks in West African countries. Human patients can develop lethal hemorrhagic fever in severe cases. Although Lassa virus is one of the most alarming pathogens from a public health perspective, there are few available countermeasures, such as antiviral drugs or vaccines. Moreover, the fact that animal models are not readily accessible and the fact that mostly laboratory viruses, which have been passaged many times after isolation, are used for studies further limits the successful development of countermeasures. In this study, we demonstrate that a human isolate of Lassa virus causes lethal infection uniformly in Hartley guinea pigs. This novel animal model of Lassa fever may contribute to Lassa fever research and the development of vaccines and therapeutics.Junki MaruyamaJohn T. ManningElizabeth J. MateerRachel SattlerNatalya BukreyevaCheng HuangSlobodan PaesslerAmerican Society for MicrobiologyarticleLassa virusguinea piganimal modelclinical isolateMicrobiologyQR1-502ENmSphere, Vol 4, Iss 5 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Lassa virus guinea pig animal model clinical isolate Microbiology QR1-502
spellingShingle	Lassa virus guinea pig animal model clinical isolate Microbiology QR1-502 Junki Maruyama John T. Manning Elizabeth J. Mateer Rachel Sattler Natalya Bukreyeva Cheng Huang Slobodan Paessler Lethal Infection of Lassa Virus Isolated from a Human Clinical Sample in Outbred Guinea Pigs without Adaptation
description	ABSTRACT Lassa virus (LASV), a member of the family Arenaviridae, is the causative agent of Lassa fever. Lassa virus is endemic in West African countries, such as Nigeria, Guinea, Liberia, and Sierra Leone, and causes outbreaks annually. Lassa fever onset begins with “flu-like” symptoms and may develop into lethal hemorrhagic disease in severe cases. Although Lassa virus is one of the most alarming pathogens from a public health perspective, there are few licensed vaccines or therapeutics against Lassa fever. The fact that animal models are limited and the fact that mostly laboratory-derived viruses are used for studies limit the successful development of countermeasures. In this study, we demonstrated that the LASV isolate LF2384-NS-DIA-1 (LF2384), which was directly isolated from a serum sample from a fatal human Lassa fever case in the 2012 Sierra Leone outbreak, causes uniformly lethal infection in outbred Hartley guinea pigs without virus-host adaptation. This is the first report of a clinically isolated strain of LASV causing lethal infection in outbred guinea pigs. This novel guinea pig model of Lassa fever may contribute to Lassa fever research and the development of vaccines and therapeutics. IMPORTANCE Lassa virus, the causative agent of Lassa fever, is a zoonotic pathogen causing annual outbreaks in West African countries. Human patients can develop lethal hemorrhagic fever in severe cases. Although Lassa virus is one of the most alarming pathogens from a public health perspective, there are few available countermeasures, such as antiviral drugs or vaccines. Moreover, the fact that animal models are not readily accessible and the fact that mostly laboratory viruses, which have been passaged many times after isolation, are used for studies further limits the successful development of countermeasures. In this study, we demonstrate that a human isolate of Lassa virus causes lethal infection uniformly in Hartley guinea pigs. This novel animal model of Lassa fever may contribute to Lassa fever research and the development of vaccines and therapeutics.
format	article
author	Junki Maruyama John T. Manning Elizabeth J. Mateer Rachel Sattler Natalya Bukreyeva Cheng Huang Slobodan Paessler
author_facet	Junki Maruyama John T. Manning Elizabeth J. Mateer Rachel Sattler Natalya Bukreyeva Cheng Huang Slobodan Paessler
author_sort	Junki Maruyama
title	Lethal Infection of Lassa Virus Isolated from a Human Clinical Sample in Outbred Guinea Pigs without Adaptation
title_short	Lethal Infection of Lassa Virus Isolated from a Human Clinical Sample in Outbred Guinea Pigs without Adaptation
title_full	Lethal Infection of Lassa Virus Isolated from a Human Clinical Sample in Outbred Guinea Pigs without Adaptation
title_fullStr	Lethal Infection of Lassa Virus Isolated from a Human Clinical Sample in Outbred Guinea Pigs without Adaptation
title_full_unstemmed	Lethal Infection of Lassa Virus Isolated from a Human Clinical Sample in Outbred Guinea Pigs without Adaptation
title_sort	lethal infection of lassa virus isolated from a human clinical sample in outbred guinea pigs without adaptation
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/8da41667acbb4114929cd424d03417fa
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Lethal Infection of Lassa Virus Isolated from a Human Clinical Sample in Outbred Guinea Pigs without Adaptation

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