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Ectromelia Virus Disease Characterization in the BALB/c Mouse: A Surrogate Model for Assessment of Smallpox Medical Countermeasures

In 2007, the United States– Food and Drug Administration (FDA) issued guidance concerning animal models for testing the efficacy of medical countermeasures against variola virus (VARV), the etiologic agent for smallpox. Ectromelia virus (ECTV) is naturally-occurring and responsible for severe mortal...

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Autores principales: Garver, Jennifer, Weber, Lauren, Vela, Eric M., Anderson, Mike, Warren, Richard, Merchlinsky, Michael, Houchens, Christopher, Rogers, James V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4974538/
https://www.ncbi.nlm.nih.gov/pubmed/27455306
http://dx.doi.org/10.3390/v8070203
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author Garver, Jennifer
Weber, Lauren
Vela, Eric M.
Anderson, Mike
Warren, Richard
Merchlinsky, Michael
Houchens, Christopher
Rogers, James V.
author_facet Garver, Jennifer
Weber, Lauren
Vela, Eric M.
Anderson, Mike
Warren, Richard
Merchlinsky, Michael
Houchens, Christopher
Rogers, James V.
author_sort Garver, Jennifer
collection PubMed
description In 2007, the United States– Food and Drug Administration (FDA) issued guidance concerning animal models for testing the efficacy of medical countermeasures against variola virus (VARV), the etiologic agent for smallpox. Ectromelia virus (ECTV) is naturally-occurring and responsible for severe mortality and morbidity as a result of mousepox disease in the murine model, displaying similarities to variola infection in humans. Due to the increased need of acceptable surrogate animal models for poxvirus disease, we have characterized ECTV infection in the BALB/c mouse. Mice were inoculated intranasally with a high lethal dose (125 PFU) of ECTV, resulting in complete mortality 10 days after infection. Decreases in weight and temperature from baseline were observed eight to nine days following infection. Viral titers via quantitative polymerase chain reaction (qPCR) and plaque assay were first observed in the blood at 4.5 days post-infection and in tissue (spleen and liver) at 3.5 days post-infection. Adverse clinical signs of disease were first observed four and five days post-infection, with severe signs occurring on day 7. Pathological changes consistent with ECTV infection were first observed five days after infection. Examination of data obtained from these parameters suggests the ECTV BALB/c model is suitable for potential use in medical countermeasures (MCMs) development and efficacy testing.
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spelling pubmed-49745382016-08-08 Ectromelia Virus Disease Characterization in the BALB/c Mouse: A Surrogate Model for Assessment of Smallpox Medical Countermeasures Garver, Jennifer Weber, Lauren Vela, Eric M. Anderson, Mike Warren, Richard Merchlinsky, Michael Houchens, Christopher Rogers, James V. Viruses Article In 2007, the United States– Food and Drug Administration (FDA) issued guidance concerning animal models for testing the efficacy of medical countermeasures against variola virus (VARV), the etiologic agent for smallpox. Ectromelia virus (ECTV) is naturally-occurring and responsible for severe mortality and morbidity as a result of mousepox disease in the murine model, displaying similarities to variola infection in humans. Due to the increased need of acceptable surrogate animal models for poxvirus disease, we have characterized ECTV infection in the BALB/c mouse. Mice were inoculated intranasally with a high lethal dose (125 PFU) of ECTV, resulting in complete mortality 10 days after infection. Decreases in weight and temperature from baseline were observed eight to nine days following infection. Viral titers via quantitative polymerase chain reaction (qPCR) and plaque assay were first observed in the blood at 4.5 days post-infection and in tissue (spleen and liver) at 3.5 days post-infection. Adverse clinical signs of disease were first observed four and five days post-infection, with severe signs occurring on day 7. Pathological changes consistent with ECTV infection were first observed five days after infection. Examination of data obtained from these parameters suggests the ECTV BALB/c model is suitable for potential use in medical countermeasures (MCMs) development and efficacy testing. MDPI 2016-07-22 /pmc/articles/PMC4974538/ /pubmed/27455306 http://dx.doi.org/10.3390/v8070203 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Garver, Jennifer
Weber, Lauren
Vela, Eric M.
Anderson, Mike
Warren, Richard
Merchlinsky, Michael
Houchens, Christopher
Rogers, James V.
Ectromelia Virus Disease Characterization in the BALB/c Mouse: A Surrogate Model for Assessment of Smallpox Medical Countermeasures
title Ectromelia Virus Disease Characterization in the BALB/c Mouse: A Surrogate Model for Assessment of Smallpox Medical Countermeasures
title_full Ectromelia Virus Disease Characterization in the BALB/c Mouse: A Surrogate Model for Assessment of Smallpox Medical Countermeasures
title_fullStr Ectromelia Virus Disease Characterization in the BALB/c Mouse: A Surrogate Model for Assessment of Smallpox Medical Countermeasures
title_full_unstemmed Ectromelia Virus Disease Characterization in the BALB/c Mouse: A Surrogate Model for Assessment of Smallpox Medical Countermeasures
title_short Ectromelia Virus Disease Characterization in the BALB/c Mouse: A Surrogate Model for Assessment of Smallpox Medical Countermeasures
title_sort ectromelia virus disease characterization in the balb/c mouse: a surrogate model for assessment of smallpox medical countermeasures
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4974538/
https://www.ncbi.nlm.nih.gov/pubmed/27455306
http://dx.doi.org/10.3390/v8070203
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