title: Intrabronchial inoculation of cynomolgus macaques with cowpox virus.
abstract: The public health threat of orthopoxviruses from bioterrorist attacks has prompted researchers to develop suitable animal models for increasing our understanding of viral pathogenesis and evaluation of medical countermeasures (MCMs) in compliance with the FDA Animal Efficacy Rule. We present an accessible intrabronchial cowpox virus (CPXV) model that can be evaluated under biosafety level-2 laboratory conditions. In this dose-ranging study, utilizing cynomolgus macaques, signs of typical orthopoxvirus disease were observed with the lymphoid organs, liver, skin (generally mild) and respiratory tract as target tissues. Clinical and histopathological evaluation suggests that intrabronchial CPXV recapitulated many of the features of monkeypox and variola virus, the causative agent of smallpox, infections in cynomolgus macaque models. These similarities suggest that CPXV infection in non-human primates should be pursued further as an alternative model of smallpox. Further development of the CPXV primate model, unimpeded by select agent and biocontainment restrictions, should facilitate the development of MCMs for smallpox.
authors.affiliation: Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Alvin L
authors.initials: AL
authors.lastname: Smith
authors.affiliation: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
authors.forename: Marisa
authors.initials: M
authors.lastname: St Claire
authors.affiliation: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
authors.forename: Srikanth
authors.initials: S
authors.lastname: Yellayi
authors.affiliation: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Bollinger
authors.affiliation: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.|Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Jahrling
authors.affiliation: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Paragas
authors.affiliation: Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Blaney
authors.affiliation: Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Reed F
authors.initials: RF
authors.lastname: Johnson
mesh_terms: D000818:Animals; D003264:Containment of Biohazards; D015605:Cowpox / Q000473:pathology / Q000821:virology*; D015608:Cowpox virus / Q000472:pathogenicity* / Q000502:physiology; D004195:Disease Models, Animal; D006801:Humans; D008252:Macaca fascicularis; D012899:Smallpox / Q000473:pathology / Q000821:virology; D014774:Virulence