Proportional mouse model for aerosol infection by influenza
Identifieur interne : 000273 ( Istex/Corpus ); précédent : 000272; suivant : 000274Proportional mouse model for aerosol infection by influenza
Auteurs : R. S. Mcdonald ; A. R. Sambol ; B. K. Heimbuch ; T. L. Brown ; S. H. Hinrichs ; J. D. WanderSource :
- Journal of Applied Microbiology [ 1364-5072 ] ; 2012-10.
English descriptors
- Teeft :
- Additional studies, Aerosol, Aerosol concentration, Aerosol exposure, Aerosol exposures, Aerosol studies, Aerosol test system, Aerosol transmission, Animal model, Animal models, Appl, Appl microbiol, Assay, Average weights, Bioaerosol, Biological safety cabinet, Biotechnol bioeng, Boca raton, Cell culture plates, Charge neutralizer, Clinical effect, Coli phage, Collison, Collison nebulizer, Control mice, Cycle threshold, Cytopathic effect, Days postexposure, Different exposure times, Diffusion drier, Dilution, Dilution series, Direct correlation, Dos, Dose, Droplet nuclei, Drug discov today, Exposure group, Exposure time, Exposure time points, Exposure times, Female mice, Force research laboratory, Government works, Government works mcdonald, Homogenate, Human beings, Immune response, Infection, Infectivity, Inhalation, Inhalation exposure system, Inhalation exposure systems, Inhalation toxicology, International commission, Intranasal inoculation, Lter, Lter holder, Lter media, Lter medium, Lung homogenates, Lung tissue, Maximum exposure time, Mcdonald, Mdck cells, Microbiology, Mouse, Mouse lung image, Mouse model, Murine lung tissue, National academies press, Nebulizer, Pandemic, Polycarbonate tubes, Proc natl acad, Proportional mouse infection model, Radiological protection, Size range, Standard cell culture techniques, Susceptibility, Tellier, Time point, Time points, Uorescent antibody assay, Viral, Viral populations, Virus, Virus infection, Virus infections, Virus replication, Weight change, Weight loss.
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.
Url:
DOI: 10.1111/j.1365-2672.2012.05402.x
Links to Exploration step
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<front><div type="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.</div>
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<profileDesc><abstract style="main" xml:id="jam5402-abs-0001"><head>Abstract</head>
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<p>The aim of this study was to demonstrate a prototype tool for measuring infectivity of an aerosolized human pathogen – influenza <hi rend="fc">A</hi>
/<hi rend="fc">PR</hi>
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1<hi rend="fc">N</hi>
1 virus into <hi rend="fc">C</hi>
57<hi rend="fc">BL</hi>
,<hi rend="fc"> BALB</hi>
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<hi rend="subscript">50</hi>
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<head>Significance and Impact of the Study</head>
<p>In the <hi rend="fc">CATS</hi>
, 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.</p>
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<p>Intranasal inoculation of nonadapted <fc>H</fc>
1<fc>N</fc>
1 virus into <fc>C</fc>
57<fc>BL</fc>
,<fc> BALB</fc>
/c and <fc>CD</fc>
‐1 mice caused infection in all three species. Respiratory exposure of <fc>CD</fc>
‐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 <fc>DNA</fc>
amplification (qRT‐<fc>PCR</fc>
), direct fluorescence and microscopic evaluation of cytopathic effect. Plots of weight change and of <fc>PCR</fc>
cycle threshold vs delivered dose were linear to threshold doses of ~40 <fc>TCID</fc>
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<p>In the <fc>CATS</fc>
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<affiliation>University of Nebraska Medical Center, 985900 Nebraska Medical Center, NE, Omaha, USA</affiliation>
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<affiliation>Airbase Sciences Branch, Air Force Research Laboratory, Tyndall AFB, FL, USA</affiliation>
<affiliation>CorrespondenceJoseph Wander, Air Force Research Laboratory, 139 Barnes Drive, Suite 2, Tyndall AFB, FL 32403. E‐mail:</affiliation>
<affiliation>E-mail: joseph.wander@us.af.mil</affiliation>
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<genre type="article" displayLabel="article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-6N5SZHKN-D">article</genre>
<originInfo><publisher>Blackwell Publishing Ltd</publisher>
<dateIssued encoding="w3cdtf">2012-10</dateIssued>
<dateCreated encoding="w3cdtf">2012-07-27</dateCreated>
<dateCaptured encoding="w3cdtf">2012-02-22</dateCaptured>
<dateValid encoding="w3cdtf">2012-07-16</dateValid>
<copyrightDate encoding="w3cdtf">2012</copyrightDate>
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<language><languageTerm type="code" authority="rfc3066">en</languageTerm>
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<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.</abstract>
<note type="funding">Defence Threat Reduction Agency</note>
<note type="funding">Biological Advanced Research and Development Authority (BARDA)</note>
<note type="funding">The Air Force Research Laboratory (AFRL)</note>
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<topic>aerosol</topic>
<topic>H1N1</topic>
<topic>infection</topic>
<topic>influenza</topic>
<topic>inhalation</topic>
<topic>mouse</topic>
<topic>respiratory protection</topic>
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