Teaching a new mouse old tricks: Humanized mice as an infection model for Variola virus.

Smallpox, caused by the solely human pathogen Variola virus (VARV), was declared eradicated in 1980. While known VARV stocks are secure, smallpox remains a bioterrorist threat agent. Recent U.S. Food and Drug Administration approval of the first smallpox anti-viral (tecovirimat) therapeutic was a su...

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Autores principales:	Christina L Hutson, Ashley V Kondas, Jana M Ritter, Zachary Reed, Sharon Dietz Ostergaard, Clint N Morgan, Nadia Gallardo-Romero, Cassandra Tansey, Matthew R Mauldin, Johanna S Salzer, Christine M Hughes, Cynthia S Goldsmith, Darin Carroll, Victoria A Olson
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/9e0446caa7794c65aa4b99c44e348d8c
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spelling	oai:doaj.org-article:9e0446caa7794c65aa4b99c44e348d8c2021-12-02T20:00:07ZTeaching a new mouse old tricks: Humanized mice as an infection model for Variola virus.1553-73661553-737410.1371/journal.ppat.1009633https://doaj.org/article/9e0446caa7794c65aa4b99c44e348d8c2021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009633https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Smallpox, caused by the solely human pathogen Variola virus (VARV), was declared eradicated in 1980. While known VARV stocks are secure, smallpox remains a bioterrorist threat agent. Recent U.S. Food and Drug Administration approval of the first smallpox anti-viral (tecovirimat) therapeutic was a successful step forward in smallpox preparedness; however, orthopoxviruses can become resistant to treatment, suggesting a multi-therapeutic approach is necessary. Animal models are required for testing medical countermeasures (MCMs) and ideally MCMs are tested directly against the pathogen of interest. Since VARV only infects humans, a representative animal model for testing therapeutics directly against VARV remains a challenge. Here we show that three different humanized mice strains are highly susceptible to VARV infection, establishing the first small animal model using VARV. In comparison, the non-humanized, immunosuppressed background mouse was not susceptible to systemic VARV infection. Following an intranasal VARV challenge that mimics the natural route for human smallpox transmission, the virus spread systemically within the humanized mouse before mortality (~ 13 days post infection), similar to the time from exposure to symptom onset for ordinary human smallpox. Our identification of a permissive/representative VARV animal model can facilitate testing of MCMs in a manner consistent with their intended use.Christina L HutsonAshley V KondasJana M RitterZachary ReedSharon Dietz OstergaardClint N MorganNadia Gallardo-RomeroCassandra TanseyMatthew R MauldinJohanna S SalzerChristine M HughesCynthia S GoldsmithDarin CarrollVictoria A OlsonPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 9, p e1009633 (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 Christina L Hutson Ashley V Kondas Jana M Ritter Zachary Reed Sharon Dietz Ostergaard Clint N Morgan Nadia Gallardo-Romero Cassandra Tansey Matthew R Mauldin Johanna S Salzer Christine M Hughes Cynthia S Goldsmith Darin Carroll Victoria A Olson Teaching a new mouse old tricks: Humanized mice as an infection model for Variola virus.
description	Smallpox, caused by the solely human pathogen Variola virus (VARV), was declared eradicated in 1980. While known VARV stocks are secure, smallpox remains a bioterrorist threat agent. Recent U.S. Food and Drug Administration approval of the first smallpox anti-viral (tecovirimat) therapeutic was a successful step forward in smallpox preparedness; however, orthopoxviruses can become resistant to treatment, suggesting a multi-therapeutic approach is necessary. Animal models are required for testing medical countermeasures (MCMs) and ideally MCMs are tested directly against the pathogen of interest. Since VARV only infects humans, a representative animal model for testing therapeutics directly against VARV remains a challenge. Here we show that three different humanized mice strains are highly susceptible to VARV infection, establishing the first small animal model using VARV. In comparison, the non-humanized, immunosuppressed background mouse was not susceptible to systemic VARV infection. Following an intranasal VARV challenge that mimics the natural route for human smallpox transmission, the virus spread systemically within the humanized mouse before mortality (~ 13 days post infection), similar to the time from exposure to symptom onset for ordinary human smallpox. Our identification of a permissive/representative VARV animal model can facilitate testing of MCMs in a manner consistent with their intended use.
format	article
author	Christina L Hutson Ashley V Kondas Jana M Ritter Zachary Reed Sharon Dietz Ostergaard Clint N Morgan Nadia Gallardo-Romero Cassandra Tansey Matthew R Mauldin Johanna S Salzer Christine M Hughes Cynthia S Goldsmith Darin Carroll Victoria A Olson
author_facet	Christina L Hutson Ashley V Kondas Jana M Ritter Zachary Reed Sharon Dietz Ostergaard Clint N Morgan Nadia Gallardo-Romero Cassandra Tansey Matthew R Mauldin Johanna S Salzer Christine M Hughes Cynthia S Goldsmith Darin Carroll Victoria A Olson
author_sort	Christina L Hutson
title	Teaching a new mouse old tricks: Humanized mice as an infection model for Variola virus.
title_short	Teaching a new mouse old tricks: Humanized mice as an infection model for Variola virus.
title_full	Teaching a new mouse old tricks: Humanized mice as an infection model for Variola virus.
title_fullStr	Teaching a new mouse old tricks: Humanized mice as an infection model for Variola virus.
title_full_unstemmed	Teaching a new mouse old tricks: Humanized mice as an infection model for Variola virus.
title_sort	teaching a new mouse old tricks: humanized mice as an infection model for variola virus.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/9e0446caa7794c65aa4b99c44e348d8c
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Teaching a new mouse old tricks: Humanized mice as an infection model for Variola virus.

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