Proportional mouse model for aerosol infection by influenza

• Published in: Journal of applied microbiology Vol. 113; no. 4; pp. 767 - 778
• Main Authors: McDonald, R.S., Sambol, A.R., Heimbuch, B.K., Brown, T.L., Hinrichs, S.H., Wander, J.D.
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell Publishing Ltd 01-10-2012; Blackwell; Oxford University Press; John Wiley and Sons Inc
• Subjects: Administration, Inhalation; Administration, Intranasal; aerosol; Aerosols; Aerosols - adverse effects; Animals; Atmosphere Exposure Chambers; Biological and medical sciences; Disease Models, Animal; Female; Fundamental and applied biological sciences. Psychology; H1N1; infection; Influenza; Influenza A Virus, H1N1 Subtype - pathogenicity; inhalation; Inhalation Exposure; Lung - pathology; Lung - virology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Microbiology; mouse; Original; Pathology; respiratory protection; Rodents; Applied microbiology; Rodentia; H1N1; Inhalation; Infection; Vertebrata; Mammalia; Mouse; Viral disease; Influenza; Aerosols; Models; Respiration; respiratory protection; Protection; aerosol
• ISSN: 1364-5072; 1365-2672
• DOI: 10.1111/j.1365-2672.2012.05402.x

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.