Evaluation of Virulence in Cynomolgus Macaques Using a Virus Preparation Enriched for the Extracellular Form of Monkeypox Virus
The 2022 global human monkeypox outbreak emphasizes the importance of maintaining poxvirus research, including enriching a basic understanding of animal models for developing and advancing therapeutics and vaccines. Intravenous administration of monkeypox virus in macaques is arguably one of the bes...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-09-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/14/9/1993 |
| _version_ | 1827655776257179648 |
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| author | Eric M. Mucker Josh D. Shamblin Arthur J. Goff Todd M. Bell Christopher Reed Nancy A. Twenhafel Jennifer Chapman Marc Mattix Derron Alves Robert F. Garry Lisa E. Hensley |
| author_facet | Eric M. Mucker Josh D. Shamblin Arthur J. Goff Todd M. Bell Christopher Reed Nancy A. Twenhafel Jennifer Chapman Marc Mattix Derron Alves Robert F. Garry Lisa E. Hensley |
| author_sort | Eric M. Mucker |
| collection | DOAJ |
| description | The 2022 global human monkeypox outbreak emphasizes the importance of maintaining poxvirus research, including enriching a basic understanding of animal models for developing and advancing therapeutics and vaccines. Intravenous administration of monkeypox virus in macaques is arguably one of the best animal models for evaluating the efficacy of medical countermeasures. Here we addressed one criticism of the model, a requirement for a high-titer administration of virus, as well as improving our understanding of monkeypox virus pathogenesis. To do so, we infected macaques with a challenge dose containing a characterized inoculum enriched for the extracellular form of monkeypox virus. Although there were some differences between diseases caused by the enriched preparation compared with a relatively similar unpurified preparation, we were unable to reduce the viral input with the enriched preparation and maintain severe disease. We found that inherent factors contained within the serum of nonhuman primate blood affect the stability of the monkeypox extracellular virions. As a first step to study a role of the extracellular form in transmission, we also showed the presence of this form in the oropharyngeal swabs from nonhuman primates exposed to monkeypox virus. |
| first_indexed | 2024-03-09T22:13:24Z |
| format | Article |
| id | doaj.art-7488b9220c6a4b1d88e581edb248f6c2 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T22:13:24Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-7488b9220c6a4b1d88e581edb248f6c22023-11-23T19:27:45ZengMDPI AGViruses1999-49152022-09-01149199310.3390/v14091993Evaluation of Virulence in Cynomolgus Macaques Using a Virus Preparation Enriched for the Extracellular Form of Monkeypox VirusEric M. Mucker0Josh D. Shamblin1Arthur J. Goff2Todd M. Bell3Christopher Reed4Nancy A. Twenhafel5Jennifer Chapman6Marc Mattix7Derron Alves8Robert F. Garry9Lisa E. Hensley10United States Army Medical Research Institute of Infectious Diseases, Virology Division, Fort Detrick, Frederick, MD 21702, USAUnited States Army Medical Research Institute of Infectious Diseases, Virology Division, Fort Detrick, Frederick, MD 21702, USAUnited States Army Medical Research Institute of Infectious Diseases, Virology Division, Fort Detrick, Frederick, MD 21702, USAUnited States Army Medical Research Institute of Infectious Diseases, Pathology Division, Fort Detrick, Frederick, MD 21702, USAUnited States Army Medical Research Institute of Infectious Diseases, Pathology Division, Fort Detrick, Frederick, MD 21702, USAUnited States Army Medical Research Institute of Infectious Diseases, Pathology Division, Fort Detrick, Frederick, MD 21702, USAUnited States Army Medical Research Institute of Infectious Diseases, Pathology Division, Fort Detrick, Frederick, MD 21702, USAUnited States Army Medical Research Institute of Infectious Diseases, Pathology Division, Fort Detrick, Frederick, MD 21702, USANational Institutes of Health, National Institute of Allergy and Infectious Diseases, Infectious Disease Pathogenesis Section, Rockville, MD 20852, USADepartment of Microbiology and Immunology, School of Medicine, Tulane University, New Orleans, LA 70112, USAUnited States Department of Agriculture, Zoonotic and Emerging Disease Unit, Manhattan, KS 66505, USAThe 2022 global human monkeypox outbreak emphasizes the importance of maintaining poxvirus research, including enriching a basic understanding of animal models for developing and advancing therapeutics and vaccines. Intravenous administration of monkeypox virus in macaques is arguably one of the best animal models for evaluating the efficacy of medical countermeasures. Here we addressed one criticism of the model, a requirement for a high-titer administration of virus, as well as improving our understanding of monkeypox virus pathogenesis. To do so, we infected macaques with a challenge dose containing a characterized inoculum enriched for the extracellular form of monkeypox virus. Although there were some differences between diseases caused by the enriched preparation compared with a relatively similar unpurified preparation, we were unable to reduce the viral input with the enriched preparation and maintain severe disease. We found that inherent factors contained within the serum of nonhuman primate blood affect the stability of the monkeypox extracellular virions. As a first step to study a role of the extracellular form in transmission, we also showed the presence of this form in the oropharyngeal swabs from nonhuman primates exposed to monkeypox virus.https://www.mdpi.com/1999-4915/14/9/1993orthopoxvirusextracellular virionnonhuman primatesviremiamodelsmallpox |
| spellingShingle | Eric M. Mucker Josh D. Shamblin Arthur J. Goff Todd M. Bell Christopher Reed Nancy A. Twenhafel Jennifer Chapman Marc Mattix Derron Alves Robert F. Garry Lisa E. Hensley Evaluation of Virulence in Cynomolgus Macaques Using a Virus Preparation Enriched for the Extracellular Form of Monkeypox Virus Viruses orthopoxvirus extracellular virion nonhuman primates viremia model smallpox |
| title | Evaluation of Virulence in Cynomolgus Macaques Using a Virus Preparation Enriched for the Extracellular Form of Monkeypox Virus |
| title_full | Evaluation of Virulence in Cynomolgus Macaques Using a Virus Preparation Enriched for the Extracellular Form of Monkeypox Virus |
| title_fullStr | Evaluation of Virulence in Cynomolgus Macaques Using a Virus Preparation Enriched for the Extracellular Form of Monkeypox Virus |
| title_full_unstemmed | Evaluation of Virulence in Cynomolgus Macaques Using a Virus Preparation Enriched for the Extracellular Form of Monkeypox Virus |
| title_short | Evaluation of Virulence in Cynomolgus Macaques Using a Virus Preparation Enriched for the Extracellular Form of Monkeypox Virus |
| title_sort | evaluation of virulence in cynomolgus macaques using a virus preparation enriched for the extracellular form of monkeypox virus |
| topic | orthopoxvirus extracellular virion nonhuman primates viremia model smallpox |
| url | https://www.mdpi.com/1999-4915/14/9/1993 |
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