title: Small particle aerosol inoculation of cowpox Brighton Red in rhesus monkeys results in a severe respiratory disease.
abstract: Cowpox virus (CPXV) inoculation of nonhuman primates (NHPs) has been suggested as an alternate model for smallpox (Kramski et al., 2010, PLoS One, 5, e10412). Previously, we have demonstrated that intrabronchial inoculation of CPXV-Brighton Red (CPXV-BR) into cynomolgus monkeys resulted in a disease that shared many similarities to smallpox; however, severe respiratory tract disease was observed (Smith et al., 2011, J. Gen. Virol.). Here we describe the course of disease after small particle aerosol exposure of rhesus monkeys using computed tomography (CT) to monitor respiratory disease progression. Subjects developed a severe respiratory disease that was uniformly lethal at 5.7 log10 PFU of CPXV-BR. CT indicated changes in lung architecture that correlated with changes in peripheral blood monocytes and peripheral oxygen saturation. While the small particle aerosol inoculation route does not accurately mimic human smallpox, the data suggest that CT can be used as a tool to monitor real-time disease progression for evaluation of animal models for human diseases.
authors.affiliation: Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
authors.forename: Reed F
authors.initials: RF
authors.lastname: Johnson
authors.affiliation: Center for Infectious Disease Imaging, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Dima A
authors.initials: DA
authors.lastname: Hammoud
authors.affiliation: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Lackemeyer
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: Center for Infectious Disease Imaging, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Solomon
authors.affiliation: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
authors.forename: Jordan K
authors.initials: JK
authors.lastname: Bohannon
authors.affiliation: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
authors.forename: Krisztina B
authors.initials: KB
authors.lastname: Janosko
authors.affiliation: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Jett
authors.affiliation: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
authors.forename: Kurt
authors.initials: K
authors.lastname: Cooper
authors.affiliation: Office of the Scientific Director, 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, Frederick, MD 21702, USA; Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Jahrling
mesh_terms: D000336:Aerosols / Q000032:analysis; D000818:Animals; D015605:Cowpox / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000821:virology; D015608:Cowpox virus / Q000472:pathogenicity / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D009000:Monocytes / Q000821:virology; D012137:Respiratory System / Q000276:immunology / Q000473:pathology / Q000821:virology; D012140:Respiratory Tract Diseases / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000821:virology*; D014774:Virulence
chemical_list: D000336:Aerosols
keywords: Aerosol inoculation; Animal model; CT; Computed tomography; Cowpox; Orthopoxvirus; Pathogenesis