Proportional mouse model for aerosol infection by influenza

Authors

R. S. McDonald, Applied Research Associates, Inc.
A. R. Sambol, University of Nebraska Medical CenterFollow
B. K. Heimbuch, Applied Research Associates, Inc.
T. L. Brown, University of Nebraska Medical Center
S. H. Hinrichs, University of Nebraska Medical CenterFollow
J. D. Wander, Air Force Research LaboratoryFollow

Document Type

Article

Date of this Version

2012

Citation

Journal of Applied Microbiology 113, 767--778

Comments

© 2012 The Society for Applied Microbiology

No claim to US Government works

doi:10.1111/j.1365-2672.2012.05402.x

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.