Small particle aerosol inoculation of cowpox Brighton Red in rhesus monkeys results in a severe respiratory disease

Virology. 2015 Jul:481:124-35. doi: 10.1016/j.virol.2015.02.044. Epub 2015 Mar 14.

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.

Keywords: Aerosol inoculation; Animal model; CT; Computed tomography; Cowpox; Orthopoxvirus; Pathogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Aerosols / analysis
  • Animals
  • Cowpox / immunology
  • Cowpox / mortality
  • Cowpox / pathology
  • Cowpox / virology
  • Cowpox virus / pathogenicity
  • Cowpox virus / physiology*
  • Disease Models, Animal*
  • Female
  • Humans
  • Macaca mulatta*
  • Male
  • Monocytes / virology
  • Respiratory System / immunology
  • Respiratory System / pathology
  • Respiratory System / virology
  • Respiratory Tract Diseases / immunology
  • Respiratory Tract Diseases / mortality
  • Respiratory Tract Diseases / pathology
  • Respiratory Tract Diseases / virology*
  • Virulence

Substances

  • Aerosols