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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 log{sub 10} 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. - Highlights: • Small particle aerosol exposure of rhesus results in a severe respiratory disease. • CT findings correlated with peripheral oxygen saturation and monocyte increases. • Virus dissemination was limited and mainly confined to the respiratory tract. • CT providesmore » insight into pathogenesis to aid development of animal models of disease.« less

Authors:
 [1];  [2]; ;  [3];  [2]; ; ; ;  [3];  [4];  [1];  [5]
  1. Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702 (United States)
  2. Center for Infectious Disease Imaging, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD 20892 (United States)
  3. Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702 (United States)
  4. Office of the Scientific Director, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 (United States)
  5. (United States)
Publication Date:
OSTI Identifier:
22470175
Resource Type:
Journal Article
Resource Relation:
Journal Name: Virology; Journal Volume: 481; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AEROSOLS; COMPUTERIZED TOMOGRAPHY; DISEASES; INOCULATION; LUNGS; MACACUS; MONOCYTES; OXYGEN; PARTICLES; PATHOGENESIS; VIRUSES

Citation Formats

Johnson, Reed F., Hammoud, Dima A., Lackemeyer, Matthew G., Yellayi, Srikanth, Solomon, Jeffrey, Bohannon, Jordan K., Janosko, Krisztina B., Jett, Catherine, Cooper, Kurt, Blaney, Joseph E., Jahrling, Peter B., and Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702. Small particle aerosol inoculation of cowpox Brighton Red in rhesus monkeys results in a severe respiratory disease. United States: N. p., 2015. Web. doi:10.1016/J.VIROL.2015.02.044.
Johnson, Reed F., Hammoud, Dima A., Lackemeyer, Matthew G., Yellayi, Srikanth, Solomon, Jeffrey, Bohannon, Jordan K., Janosko, Krisztina B., Jett, Catherine, Cooper, Kurt, Blaney, Joseph E., Jahrling, Peter B., & Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702. Small particle aerosol inoculation of cowpox Brighton Red in rhesus monkeys results in a severe respiratory disease. United States. doi:10.1016/J.VIROL.2015.02.044.
Johnson, Reed F., Hammoud, Dima A., Lackemeyer, Matthew G., Yellayi, Srikanth, Solomon, Jeffrey, Bohannon, Jordan K., Janosko, Krisztina B., Jett, Catherine, Cooper, Kurt, Blaney, Joseph E., Jahrling, Peter B., and Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702. Wed . "Small particle aerosol inoculation of cowpox Brighton Red in rhesus monkeys results in a severe respiratory disease". United States. doi:10.1016/J.VIROL.2015.02.044.
@article{osti_22470175,
title = {Small particle aerosol inoculation of cowpox Brighton Red in rhesus monkeys results in a severe respiratory disease},
author = {Johnson, Reed F. and Hammoud, Dima A. and Lackemeyer, Matthew G. and Yellayi, Srikanth and Solomon, Jeffrey and Bohannon, Jordan K. and Janosko, Krisztina B. and Jett, Catherine and Cooper, Kurt and Blaney, Joseph E. and Jahrling, Peter B. and Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702},
abstractNote = {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 log{sub 10} 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. - Highlights: • Small particle aerosol exposure of rhesus results in a severe respiratory disease. • CT findings correlated with peripheral oxygen saturation and monocyte increases. • Virus dissemination was limited and mainly confined to the respiratory tract. • CT provides insight into pathogenesis to aid development of animal models of disease.},
doi = {10.1016/J.VIROL.2015.02.044},
journal = {Virology},
number = ,
volume = 481,
place = {United States},
year = {Wed Jul 15 00:00:00 EDT 2015},
month = {Wed Jul 15 00:00:00 EDT 2015}
}
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