Proportional mouse model for aerosol infection by influenza

R. S. Mcdonald, A. R. Sambol, B. K. Heimbuch, T. L. Brown, S. H. Hinrichs, J. D. Wander

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Aims: The aim of this study was to demonstrate a prototype tool for measuring infectivity of an aerosolized human pathogen - influenza A/PR/8/34 (H1N1) virus - using a small-animal model in the Controlled Aerosol Test System (CATS). Methods and Results: Intranasal inoculation of nonadapted H1N1 virus into C57BL, BALB/c and CD-1 mice caused infection in all three species. Respiratory exposure of CD-1 mice to the aerosolized virus at graduated doses was accomplished in a modified rodent exposure apparatus. Weight change was recorded for 7 days postexposure, and viral populations in lung tissue homogenates were measured post mortem by DNA amplification (qRT-PCR), direct fluorescence and microscopic evaluation of cytopathic effect. Plots of weight change and of PCR cycle threshold vs delivered dose were linear to threshold doses of ~40 TCID50 and ~12 TCID50, respectively. Conclusions: MID50 for inspired H1N1 aerosols in CD-1 mice is between 12 and 40 TCID50; proportionality to dose of weight loss and viral populations makes the CD-1 mouse a useful model for measuring infectivity by inhalation. Significance and Impact of the Study: In the CATS, this mouse-virus model provides the first quantitative method to evaluate the ability of respiratory protective technologies to attenuate the infectivity of an inspired pathogenic aerosol.

Original languageEnglish (US)
Pages (from-to)767-778
Number of pages12
JournalJournal of Applied Microbiology
Volume113
Issue number4
DOIs
StatePublished - Oct 2012

Keywords

  • Aerosol
  • H1N1
  • Infection
  • Influenza
  • Inhalation
  • Mouse
  • Respiratory protection

ASJC Scopus subject areas

  • Biotechnology
  • Applied Microbiology and Biotechnology

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