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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| Format: | Article |
| Language: | English |
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MDPI AG
2016-07-01
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| Series: | Viruses |
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| Online Access: | http://www.mdpi.com/1999-4915/8/7/203 |
| _version_ | 1818522852172759040 |
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| author | Jennifer Garver Lauren Weber Eric M. Vela Mike Anderson Richard Warren Michael Merchlinsky Christopher Houchens James V. Rogers |
| author_facet | Jennifer Garver Lauren Weber Eric M. Vela Mike Anderson Richard Warren Michael Merchlinsky Christopher Houchens James V. Rogers |
| author_sort | Jennifer Garver |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-11T05:38:15Z |
| format | Article |
| id | doaj.art-99ca90b7f8244ebdbed5fc5cfb2ccb7a |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-12-11T05:38:15Z |
| publishDate | 2016-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-99ca90b7f8244ebdbed5fc5cfb2ccb7a2022-12-22T01:19:13ZengMDPI AGViruses1999-49152016-07-018720310.3390/v8070203v8070203Ectromelia Virus Disease Characterization in the BALB/c Mouse: A Surrogate Model for Assessment of Smallpox Medical CountermeasuresJennifer Garver0Lauren Weber1Eric M. Vela2Mike Anderson3Richard Warren4Michael Merchlinsky5Christopher Houchens6James V. Rogers7Battelle Biomedical Research Center, West Jefferson, OH 43162, USABattelle Biomedical Research Center, West Jefferson, OH 43162, USAVaccine and Gene Therapy Institute, Oregon Health and Science University, Portland, OR 97239, USABattelle Biomedical Research Center, West Jefferson, OH 43162, USABiomedical Advanced Research and Development Authority, US Department of Health and Human Services, Washington, DC 20201, USABiomedical Advanced Research and Development Authority, US Department of Health and Human Services, Washington, DC 20201, USABiomedical Advanced Research and Development Authority, US Department of Health and Human Services, Washington, DC 20201, USABattelle Biomedical Research Center, West Jefferson, OH 43162, USAIn 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.http://www.mdpi.com/1999-4915/8/7/203ectromeliaBALB/csmallpoxsurrogate modelvaccinemedical countermeasureantiviral |
| spellingShingle | Jennifer Garver Lauren Weber Eric M. Vela Mike Anderson Richard Warren Michael Merchlinsky Christopher Houchens James V. Rogers Ectromelia Virus Disease Characterization in the BALB/c Mouse: A Surrogate Model for Assessment of Smallpox Medical Countermeasures Viruses ectromelia BALB/c smallpox surrogate model vaccine medical countermeasure antiviral |
| 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 | ectromelia BALB/c smallpox surrogate model vaccine medical countermeasure antiviral |
| url | http://www.mdpi.com/1999-4915/8/7/203 |
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