Virulent infection of outbred Hartley guinea pigs with recombinant Pichinde virus as a surrogate small animal model for human Lassa fever

Arenaviruses, such as Lassa virus (LASV), can cause severe and fatal hemorrhagic fevers (e.g., Lassa fever, LF) in humans with no vaccines or therapeutics. Research on arenavirus-induced hemorrhagic fevers (AHFs) has been hampered by the highly virulent nature of these viral pathogens, which require...

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Autores principales:	Shuiyun Lan, Wun-Ju Shieh, Qinfeng Huang, Sherif R. Zaki, Yuying Liang, Hinh Ly
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2020
Materias:	arenavirus mammarenavirus lassa virus pichinde virus virulence pathogenesis pathology animal model surrogate model Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/cb66cb00a7f74bf79fae0fb30e7cd6a1
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spelling	oai:doaj.org-article:cb66cb00a7f74bf79fae0fb30e7cd6a12021-11-17T14:21:58ZVirulent infection of outbred Hartley guinea pigs with recombinant Pichinde virus as a surrogate small animal model for human Lassa fever2150-55942150-560810.1080/21505594.2020.1809328https://doaj.org/article/cb66cb00a7f74bf79fae0fb30e7cd6a12020-12-01T00:00:00Zhttp://dx.doi.org/10.1080/21505594.2020.1809328https://doaj.org/toc/2150-5594https://doaj.org/toc/2150-5608Arenaviruses, such as Lassa virus (LASV), can cause severe and fatal hemorrhagic fevers (e.g., Lassa fever, LF) in humans with no vaccines or therapeutics. Research on arenavirus-induced hemorrhagic fevers (AHFs) has been hampered by the highly virulent nature of these viral pathogens, which require high biocontainment laboratory, and the lack of an immune-competent small animal model that can recapitulate AHF disease and pathological features. Guinea pig infected with Pichinde virus (PICV), an arenavirus that does not cause disease in humans, has been established as a convenient surrogate animal model for AHFs as it can be handled in a conventional laboratory. The PICV strain P18, derived from sequential passaging of the virus 18 times in strain 13 inbred guinea pigs, causes severe febrile illness in guinea pigs that is reminiscent of lethal LF in humans. As inbred guinea pigs are not readily available and are difficult to maintain, outbred Hartley guinea pigs have been used but they show a high degree of disease heterogeneity upon virulent P18 PICV infection. Here, we describe an improved outbred guinea-pig infection model using recombinant rP18 PICV generated by reverse genetics technique followed by plaque purification, which consistently shows >90% mortality and virulent infection. Comprehensive virological, histopathological, and immunohistochemical analyses of the rP18-virus infected animals show similar features of human LASV infection. Our data demonstrate that this improved animal model can serve as a safe, affordable, and convenient surrogate small animal model for studying human LF pathogenesis and for evaluating efficacy of preventative or therapeutic approaches.Shuiyun LanWun-Ju ShiehQinfeng HuangSherif R. ZakiYuying LiangHinh LyTaylor & Francis Grouparticlearenavirusmammarenaviruslassa viruspichinde virusvirulencepathogenesispathologyanimal modelsurrogate modelInfectious and parasitic diseasesRC109-216ENVirulence, Vol 11, Iss 1, Pp 1131-1141 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	arenavirus mammarenavirus lassa virus pichinde virus virulence pathogenesis pathology animal model surrogate model Infectious and parasitic diseases RC109-216
spellingShingle	arenavirus mammarenavirus lassa virus pichinde virus virulence pathogenesis pathology animal model surrogate model Infectious and parasitic diseases RC109-216 Shuiyun Lan Wun-Ju Shieh Qinfeng Huang Sherif R. Zaki Yuying Liang Hinh Ly Virulent infection of outbred Hartley guinea pigs with recombinant Pichinde virus as a surrogate small animal model for human Lassa fever
description	Arenaviruses, such as Lassa virus (LASV), can cause severe and fatal hemorrhagic fevers (e.g., Lassa fever, LF) in humans with no vaccines or therapeutics. Research on arenavirus-induced hemorrhagic fevers (AHFs) has been hampered by the highly virulent nature of these viral pathogens, which require high biocontainment laboratory, and the lack of an immune-competent small animal model that can recapitulate AHF disease and pathological features. Guinea pig infected with Pichinde virus (PICV), an arenavirus that does not cause disease in humans, has been established as a convenient surrogate animal model for AHFs as it can be handled in a conventional laboratory. The PICV strain P18, derived from sequential passaging of the virus 18 times in strain 13 inbred guinea pigs, causes severe febrile illness in guinea pigs that is reminiscent of lethal LF in humans. As inbred guinea pigs are not readily available and are difficult to maintain, outbred Hartley guinea pigs have been used but they show a high degree of disease heterogeneity upon virulent P18 PICV infection. Here, we describe an improved outbred guinea-pig infection model using recombinant rP18 PICV generated by reverse genetics technique followed by plaque purification, which consistently shows >90% mortality and virulent infection. Comprehensive virological, histopathological, and immunohistochemical analyses of the rP18-virus infected animals show similar features of human LASV infection. Our data demonstrate that this improved animal model can serve as a safe, affordable, and convenient surrogate small animal model for studying human LF pathogenesis and for evaluating efficacy of preventative or therapeutic approaches.
format	article
author	Shuiyun Lan Wun-Ju Shieh Qinfeng Huang Sherif R. Zaki Yuying Liang Hinh Ly
author_facet	Shuiyun Lan Wun-Ju Shieh Qinfeng Huang Sherif R. Zaki Yuying Liang Hinh Ly
author_sort	Shuiyun Lan
title	Virulent infection of outbred Hartley guinea pigs with recombinant Pichinde virus as a surrogate small animal model for human Lassa fever
title_short	Virulent infection of outbred Hartley guinea pigs with recombinant Pichinde virus as a surrogate small animal model for human Lassa fever
title_full	Virulent infection of outbred Hartley guinea pigs with recombinant Pichinde virus as a surrogate small animal model for human Lassa fever
title_fullStr	Virulent infection of outbred Hartley guinea pigs with recombinant Pichinde virus as a surrogate small animal model for human Lassa fever
title_full_unstemmed	Virulent infection of outbred Hartley guinea pigs with recombinant Pichinde virus as a surrogate small animal model for human Lassa fever
title_sort	virulent infection of outbred hartley guinea pigs with recombinant pichinde virus as a surrogate small animal model for human lassa fever
publisher	Taylor & Francis Group
publishDate	2020
url	https://doaj.org/article/cb66cb00a7f74bf79fae0fb30e7cd6a1
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Virulent infection of outbred Hartley guinea pigs with recombinant Pichinde virus as a surrogate small animal model for human Lassa fever

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