Evaluation of Virulence in Cynomolgus Macaques Using a Virus Preparation Enriched for the Extracellular Form of Monkeypox Virus
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
Affiliations
Eric M. Mucker
United States Army Medical Research Institute of Infectious Diseases, Virology Division, Fort Detrick, Frederick, MD 21702, USA
Josh D. Shamblin
United States Army Medical Research Institute of Infectious Diseases, Virology Division, Fort Detrick, Frederick, MD 21702, USA
Arthur J. Goff
United States Army Medical Research Institute of Infectious Diseases, Virology Division, Fort Detrick, Frederick, MD 21702, USA
Todd M. Bell
United States Army Medical Research Institute of Infectious Diseases, Pathology Division, Fort Detrick, Frederick, MD 21702, USA
Christopher Reed
United States Army Medical Research Institute of Infectious Diseases, Pathology Division, Fort Detrick, Frederick, MD 21702, USA
Nancy A. Twenhafel
United States Army Medical Research Institute of Infectious Diseases, Pathology Division, Fort Detrick, Frederick, MD 21702, USA
Jennifer Chapman
United States Army Medical Research Institute of Infectious Diseases, Pathology Division, Fort Detrick, Frederick, MD 21702, USA
Marc Mattix
United States Army Medical Research Institute of Infectious Diseases, Pathology Division, Fort Detrick, Frederick, MD 21702, USA
Derron Alves
National Institutes of Health, National Institute of Allergy and Infectious Diseases, Infectious Disease Pathogenesis Section, Rockville, MD 20852, USA
Robert F. Garry
Department of Microbiology and Immunology, School of Medicine, Tulane University, New Orleans, LA 70112, USA
Lisa E. Hensley
United States Department of Agriculture, Zoonotic and Emerging Disease Unit, Manhattan, KS 66505, USA
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.