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
ISTEX:2133E64584CDC2AB0BC29F834171F1B56923C187Le document en format XML
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Heimbuch</name><affiliation><mods:affiliation>Applied Research Associates, Inc, FL, Panama City, USA</mods:affiliation></affiliation></author><author><name sortKey="Brown, T L" sort="Brown, T L" uniqKey="Brown T" first="T. L." last="Brown">T. L. Brown</name><affiliation><mods:affiliation>University of Nebraska Medical Center, 985900 Nebraska Medical Center, NE, Omaha, USA</mods:affiliation></affiliation></author><author><name sortKey="Hinrichs, S H" sort="Hinrichs, S H" uniqKey="Hinrichs S" first="S. H." last="Hinrichs">S. H. Hinrichs</name><affiliation><mods:affiliation>University of Nebraska Medical Center, 985900 Nebraska Medical Center, NE, Omaha, USA</mods:affiliation></affiliation></author><author><name sortKey="Wander, J D" sort="Wander, J D" uniqKey="Wander J" first="J. D." last="Wander">J. D. Wander</name><affiliation><mods:affiliation>Airbase Sciences Branch, Air Force Research Laboratory, Tyndall AFB, FL, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>CorrespondenceJoseph Wander, Air Force Research Laboratory, 139 Barnes Drive, Suite 2, Tyndall AFB, FL 32403. 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Mcdonald</name><affiliation><mods:affiliation>Applied Research Associates, Inc, FL, Panama City, USA</mods:affiliation></affiliation></author><author><name sortKey="Sambol, A R" sort="Sambol, A R" uniqKey="Sambol A" first="A. R." last="Sambol">A. R. Sambol</name><affiliation><mods:affiliation>University of Nebraska Medical Center, 985900 Nebraska Medical Center, NE, Omaha, USA</mods:affiliation></affiliation></author><author><name sortKey="Heimbuch, B K" sort="Heimbuch, B K" uniqKey="Heimbuch B" first="B. K." last="Heimbuch">B. K. Heimbuch</name><affiliation><mods:affiliation>Applied Research Associates, Inc, FL, Panama City, USA</mods:affiliation></affiliation></author><author><name sortKey="Brown, T L" sort="Brown, T L" uniqKey="Brown T" first="T. L." last="Brown">T. L. Brown</name><affiliation><mods:affiliation>University of Nebraska Medical Center, 985900 Nebraska Medical Center, NE, Omaha, USA</mods:affiliation></affiliation></author><author><name sortKey="Hinrichs, S H" sort="Hinrichs, S H" uniqKey="Hinrichs S" first="S. H." last="Hinrichs">S. H. Hinrichs</name><affiliation><mods:affiliation>University of Nebraska Medical Center, 985900 Nebraska Medical Center, NE, Omaha, USA</mods:affiliation></affiliation></author><author><name sortKey="Wander, J D" sort="Wander, J D" uniqKey="Wander J" first="J. D." last="Wander">J. D. Wander</name><affiliation><mods:affiliation>Airbase Sciences Branch, Air Force Research Laboratory, Tyndall AFB, FL, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>CorrespondenceJoseph Wander, Air Force Research Laboratory, 139 Barnes Drive, Suite 2, Tyndall AFB, FL 32403. E‐mail:</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: joseph.wander@us.af.mil</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Journal of Applied Microbiology</title><title level="j" type="alt">JOURNAL OF APPLIED MICROBIOLOGY</title><idno type="ISSN">1364-5072</idno><idno type="eISSN">1365-2672</idno><imprint><biblScope unit="vol">113</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="767">767</biblScope><biblScope unit="page" to="778">778</biblScope><biblScope unit="page-count">12</biblScope><date type="published" when="2012-10">2012-10</date></imprint><idno type="ISSN">1364-5072</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1364-5072</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Additional studies</term><term>Aerosol</term><term>Aerosol concentration</term><term>Aerosol exposure</term><term>Aerosol exposures</term><term>Aerosol studies</term><term>Aerosol test system</term><term>Aerosol transmission</term><term>Animal model</term><term>Animal models</term><term>Appl</term><term>Appl microbiol</term><term>Assay</term><term>Average weights</term><term>Bioaerosol</term><term>Biological safety cabinet</term><term>Biotechnol bioeng</term><term>Boca raton</term><term>Cell culture plates</term><term>Charge neutralizer</term><term>Clinical effect</term><term>Coli phage</term><term>Collison</term><term>Collison nebulizer</term><term>Control mice</term><term>Cycle threshold</term><term>Cytopathic effect</term><term>Days postexposure</term><term>Different exposure times</term><term>Diffusion drier</term><term>Dilution</term><term>Dilution series</term><term>Direct correlation</term><term>Dos</term><term>Dose</term><term>Droplet nuclei</term><term>Drug discov today</term><term>Exposure group</term><term>Exposure time</term><term>Exposure time points</term><term>Exposure times</term><term>Female mice</term><term>Force research laboratory</term><term>Government works</term><term>Government works mcdonald</term><term>Homogenate</term><term>Human beings</term><term>Immune response</term><term>Infection</term><term>Infectivity</term><term>Inhalation</term><term>Inhalation exposure system</term><term>Inhalation exposure systems</term><term>Inhalation toxicology</term><term>International commission</term><term>Intranasal inoculation</term><term>Lter</term><term>Lter holder</term><term>Lter media</term><term>Lter medium</term><term>Lung homogenates</term><term>Lung tissue</term><term>Maximum exposure time</term><term>Mcdonald</term><term>Mdck cells</term><term>Microbiology</term><term>Mouse</term><term>Mouse lung image</term><term>Mouse model</term><term>Murine lung tissue</term><term>National academies press</term><term>Nebulizer</term><term>Pandemic</term><term>Polycarbonate tubes</term><term>Proc natl acad</term><term>Proportional mouse infection model</term><term>Radiological protection</term><term>Size range</term><term>Standard cell culture techniques</term><term>Susceptibility</term><term>Tellier</term><term>Time point</term><term>Time points</term><term>Uorescent antibody assay</term><term>Viral</term><term>Viral populations</term><term>Virus</term><term>Virus infection</term><term>Virus infections</term><term>Virus replication</term><term>Weight change</term><term>Weight loss</term></keywords></textClass></profileDesc></teiHeader><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></front></TEI><istex><corpusName>wiley</corpusName><keywords><teeft><json:string>microbiology</json:string><json:string>infectivity</json:string><json:string>mcdonald</json:string><json:string>lter</json:string><json:string>viral</json:string><json:string>assay</json:string><json:string>collison</json:string><json:string>bioaerosol</json:string><json:string>nebulizer</json:string><json:string>inhalation</json:string><json:string>tellier</json:string><json:string>proportional mouse infection model</json:string><json:string>appl</json:string><json:string>animal models</json:string><json:string>mouse model</json:string><json:string>weight loss</json:string><json:string>mouse</json:string><json:string>exposure time</json:string><json:string>dilution series</json:string><json:string>aerosol exposure</json:string><json:string>lter holder</json:string><json:string>government works</json:string><json:string>government works mcdonald</json:string><json:string>aerosol</json:string><json:string>aerosol test system</json:string><json:string>aerosol transmission</json:string><json:string>human beings</json:string><json:string>appl microbiol</json:string><json:string>collison nebulizer</json:string><json:string>murine lung tissue</json:string><json:string>control mice</json:string><json:string>exposure group</json:string><json:string>mdck cells</json:string><json:string>dos</json:string><json:string>virus</json:string><json:string>virus infection</json:string><json:string>charge neutralizer</json:string><json:string>time point</json:string><json:string>droplet nuclei</json:string><json:string>radiological protection</json:string><json:string>intranasal inoculation</json:string><json:string>virus infections</json:string><json:string>weight change</json:string><json:string>animal model</json:string><json:string>immune response</json:string><json:string>different exposure times</json:string><json:string>lung tissue</json:string><json:string>polycarbonate tubes</json:string><json:string>infection</json:string><json:string>homogenate</json:string><json:string>susceptibility</json:string><json:string>pandemic</json:string><json:string>inhalation exposure system</json:string><json:string>maximum exposure time</json:string><json:string>average weights</json:string><json:string>aerosol studies</json:string><json:string>diffusion drier</json:string><json:string>exposure times</json:string><json:string>lter medium</json:string><json:string>time points</json:string><json:string>aerosol concentration</json:string><json:string>cell culture plates</json:string><json:string>clinical effect</json:string><json:string>standard cell culture techniques</json:string><json:string>international commission</json:string><json:string>lung homogenates</json:string><json:string>uorescent antibody assay</json:string><json:string>lter media</json:string><json:string>aerosol exposures</json:string><json:string>mouse lung image</json:string><json:string>size range</json:string><json:string>national academies press</json:string><json:string>direct correlation</json:string><json:string>cycle threshold</json:string><json:string>coli phage</json:string><json:string>additional studies</json:string><json:string>virus replication</json:string><json:string>cytopathic effect</json:string><json:string>female mice</json:string><json:string>viral populations</json:string><json:string>days postexposure</json:string><json:string>force research laboratory</json:string><json:string>inhalation exposure systems</json:string><json:string>inhalation toxicology</json:string><json:string>boca raton</json:string><json:string>drug discov today</json:string><json:string>proc natl acad</json:string><json:string>biotechnol bioeng</json:string><json:string>exposure time points</json:string><json:string>biological safety cabinet</json:string><json:string>dilution</json:string><json:string>dose</json:string></teeft></keywords><author><json:item><name>R.S. McDonald</name><affiliations><json:string>Applied Research Associates, Inc, FL, Panama City, USA</json:string></affiliations></json:item><json:item><name>A.R. Sambol</name><affiliations><json:string>University of Nebraska Medical Center, 985900 Nebraska Medical Center, NE, Omaha, USA</json:string></affiliations></json:item><json:item><name>B.K. Heimbuch</name><affiliations><json:string>Applied Research Associates, Inc, FL, Panama City, USA</json:string></affiliations></json:item><json:item><name>T.L. Brown</name><affiliations><json:string>University of Nebraska Medical Center, 985900 Nebraska Medical Center, NE, Omaha, USA</json:string></affiliations></json:item><json:item><name>S.H. Hinrichs</name><affiliations><json:string>University of Nebraska Medical Center, 985900 Nebraska Medical Center, NE, Omaha, USA</json:string></affiliations></json:item><json:item><name>J.D. Wander</name><affiliations><json:string>Airbase Sciences Branch, Air Force Research Laboratory, Tyndall AFB, FL, USA</json:string><json:string>CorrespondenceJoseph Wander, Air Force Research Laboratory, 139 Barnes Drive, Suite 2, Tyndall AFB, FL 32403. E‐mail:</json:string><json:string>E-mail: joseph.wander@us.af.mil</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>aerosol</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>H1N1</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>infection</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>influenza</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>inhalation</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>mouse</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>respiratory protection</value></json:item></subject><articleId><json:string>JAM5402</json:string></articleId><arkIstex>ark:/67375/WNG-DC82Q8J6-0</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>article</json:string></originalGenre><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><qualityIndicators><refBibsNative>true</refBibsNative><abstractWordCount>201</abstractWordCount><abstractCharCount>1346</abstractCharCount><keywordCount>7</keywordCount><score>9.412</score><pdfWordCount>7433</pdfWordCount><pdfCharCount>46502</pdfCharCount><pdfVersion>1.3</pdfVersion><pdfPageCount>12</pdfPageCount><pdfPageSize>595.276 x 788.031 pts</pdfPageSize><pdfWordsPerPage>619</pdfWordsPerPage><pdfText>true</pdfText></qualityIndicators><title>Proportional mouse model for aerosol infection by influenza</title><pmid><json:string>22809111</json:string></pmid><genre><json:string>article</json:string></genre><host><title>Journal of Applied Microbiology</title><language><json:string>unknown</json:string></language><doi><json:string>10.1111/(ISSN)1365-2672</json:string></doi><issn><json:string>1364-5072</json:string></issn><eissn><json:string>1365-2672</json:string></eissn><publisherId><json:string>JAM</json:string></publisherId><volume>113</volume><issue>4</issue><pages><first>767</first><last>778</last><total>12</total></pages><genre><json:string>journal</json:string></genre><subject><json:item><value>Original Article</value></json:item><json:item><value>Original Articles</value></json:item><json:item><value>Biodefence</value></json:item></subject></host><namedEntities><unitex><date><json:string>2009</json:string><json:string>2012-07-27</json:string></date><geogName></geogName><orgName><json:string>University of Nebraska Medical Center</json:string><json:string>WHO</json:string><json:string>BGI Inc.</json:string><json:string>Defense Threat Reduction Agency</json:string><json:string>TSI Inc., Minneapolis</json:string><json:string>Air Force Research Laboratory</json:string><json:string>International Commission on Radiological Protection (ICRP).</json:string><json:string>US Government</json:string><json:string>Department of Defence</json:string><json:string>Roche Diagnostics, Indianapolis</json:string><json:string>Panama City, FL, USA</json:string><json:string>ICRP</json:string><json:string>Aerosol Instrument Manager</json:string><json:string>University of Nebraska Medical Center Institutional Animal Care</json:string><json:string>Diagnostic Hybrids Inc., Athens</json:string><json:string>Air Force Research Laboratory, Tyndall AFB, FL USA Keywords</json:string><json:string>NRC</json:string><json:string>Society for Applied Microbiology</json:string><json:string>Triosyn Corp</json:string><json:string>CH Technologies</json:string><json:string>International Commission on Radiological Protection</json:string><json:string>Charles River Laboratories</json:string><json:string>Nebraska Medical Center, Omaha</json:string><json:string>American Type Culture Collection</json:string></orgName><orgName_funder></orgName_funder><orgName_provider></orgName_provider><persName><json:string>Franklin Lakes</json:string><json:string>T.L. 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(2009)</json:string><json:string>Tellier 2006, 2009</json:string><json:string>Schulman and Kilbourne (1963)</json:string><json:string>Szretter et al. 2006</json:string><json:string>Asgharian and Anjilvel 1998</json:string><json:string>Schrauwen et al. 2011</json:string></ref_bibl><bibl></bibl></unitex></namedEntities><ark><json:string>ark:/67375/WNG-DC82Q8J6-0</json:string></ark><categories><wos><json:string>1 - science</json:string><json:string>2 - microbiology</json:string><json:string>2 - biotechnology & applied microbiology</json:string></wos><scienceMetrix><json:string>1 - health sciences</json:string><json:string>2 - biomedical research</json:string><json:string>3 - microbiology</json:string></scienceMetrix><scopus><json:string>1 - Life Sciences</json:string><json:string>2 - Immunology and Microbiology</json:string><json:string>3 - Applied Microbiology and Biotechnology</json:string><json:string>1 - Health Sciences</json:string><json:string>2 - Medicine</json:string><json:string>3 - General Medicine</json:string><json:string>1 - Life Sciences</json:string><json:string>2 - Biochemistry, Genetics and Molecular Biology</json:string><json:string>3 - Biotechnology</json:string></scopus><inist><json:string>1 - sciences appliquees, technologies et medecines</json:string><json:string>2 - sciences biologiques et medicales</json:string><json:string>3 - sciences medicales</json:string></inist></categories><publicationDate>2012</publicationDate><copyrightDate>2012</copyrightDate><doi><json:string>10.1111/j.1365-2672.2012.05402.x</json:string></doi><id>2133E64584CDC2AB0BC29F834171F1B56923C187</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/ark:/67375/WNG-DC82Q8J6-0/fulltext.pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/ark:/67375/WNG-DC82Q8J6-0/bundle.zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/ark:/67375/WNG-DC82Q8J6-0/fulltext.tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main">Proportional mouse model for aerosol infection by influenza</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher ref="https://scientific-publisher.data.istex.fr/ark:/67375/H02-QW5Q88H5-V">Wiley Publishing Ltd</publisher><availability><licence>© 2012 The Society for Applied Microbiology No claim to US Government works</licence></availability><date type="published" when="2012-10"></date></publicationStmt><notesStmt><note type="content-type" subtype="article" source="article" scheme="https://content-type.data.istex.fr/ark:/67375/XTP-6N5SZHKN-D">article</note><note type="publication-type" subtype="journal" scheme="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</note></notesStmt><sourceDesc><biblStruct type="article"><analytic><title level="a" type="main">Proportional mouse model for aerosol infection by influenza</title><author xml:id="author-0000"><persName><forename type="first">R.S.</forename><surname>McDonald</surname></persName><affiliation><orgName type="institution">Applied Research Associates, Inc</orgName>
<address><settlement>Panama City</settlement>
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<country key="US" xml:lang="en">UNITED STATES</country></address></affiliation></author><author xml:id="author-0001"><persName><forename type="first">A.R.</forename><surname>Sambol</surname></persName><affiliation><orgName type="institution">University of Nebraska Medical Center, 985900 Nebraska Medical Center</orgName>
<address><settlement>Omaha</settlement>
<region>NE</region>
<country key="US" xml:lang="en">UNITED STATES</country></address></affiliation></author><author xml:id="author-0002"><persName><forename type="first">B.K.</forename><surname>Heimbuch</surname></persName><affiliation><orgName type="institution">Applied Research Associates, Inc</orgName>
<address><settlement>Panama City</settlement>
<region>FL</region>
<country key="US" xml:lang="en">UNITED STATES</country></address></affiliation></author><author xml:id="author-0003"><persName><forename type="first">T.L.</forename><surname>Brown</surname></persName><affiliation><orgName type="institution">University of Nebraska Medical Center, 985900 Nebraska Medical Center</orgName>
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<country key="US" xml:lang="en">UNITED STATES</country></address></affiliation></author><author xml:id="author-0004"><persName><forename type="first">S.H.</forename><surname>Hinrichs</surname></persName><affiliation><orgName type="institution">University of Nebraska Medical Center, 985900 Nebraska Medical Center</orgName>
<address><settlement>Omaha</settlement>
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<country key="US" xml:lang="en">UNITED STATES</country></address></affiliation></author><author xml:id="author-0005" role="corresp"><persName><forename type="first">J.D.</forename><surname>Wander</surname></persName><affiliation><orgName type="division">Airbase Sciences Branch, Air Force Research Laboratory</orgName>
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<ref target="http://www.tei-c.org/">We use TEI</ref></desc></application></appInfo></encodingDesc><profileDesc><abstract style="main" xml:id="jam5402-abs-0001"><head>Abstract</head><head>Aims</head><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>/8/34 (<hi rend="fc">H</hi>1<hi rend="fc">N</hi>1) virus – using a small‐animal model in the <hi rend="fc">C</hi>ontrolled <hi rend="fc">A</hi>erosol <hi rend="fc">T</hi>est <hi rend="fc">S</hi>ystem (<hi rend="fc">CATS</hi>).</p><head>Methods and Results</head><p>Intranasal inoculation of nonadapted <hi rend="fc">H</hi>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>/c and <hi rend="fc">CD</hi>‐1 mice caused infection in all three species. Respiratory exposure of <hi rend="fc">CD</hi>‐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 <hi rend="fc">DNA</hi> amplification (qRT‐<hi rend="fc">PCR</hi>), direct fluorescence and microscopic evaluation of cytopathic effect. Plots of weight change and of <hi rend="fc">PCR</hi> cycle threshold vs delivered dose were linear to threshold doses of ~40 <hi rend="fc">TCID</hi><hi rend="subscript">50</hi> and ~12 <hi rend="fc">TCID</hi><hi rend="subscript">50</hi>, respectively.</p><head>Conclusions</head><p><hi rend="fc">MID</hi><hi rend="subscript">50</hi> for inspired <hi rend="fc">H</hi>1<hi rend="fc">N</hi>1 aerosols in <hi rend="fc">CD</hi>‐1 mice is between 12 and 40 <hi rend="fc">TCID</hi><hi rend="subscript">50</hi>; proportionality to dose of weight loss and viral populations makes the <hi rend="fc">CD</hi>‐1 mouse a useful model for measuring infectivity by inhalation.</p><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></abstract><textClass><keywords><term xml:id="jam5402-kwd-0001">aerosol</term><term xml:id="jam5402-kwd-0002"><hi rend="fc">H</hi>1<hi rend="fc">N</hi>1</term><term xml:id="jam5402-kwd-0003">infection</term><term xml:id="jam5402-kwd-0004">influenza</term><term xml:id="jam5402-kwd-0005">inhalation</term><term xml:id="jam5402-kwd-0006">mouse</term><term xml:id="jam5402-kwd-0007">respiratory protection</term></keywords><keywords rend="articleCategory"><term>Original Article</term></keywords><keywords rend="tocHeading1"><term>Original Articles</term></keywords><keywords rend="tocHeading2"><term>Biodefence</term></keywords></textClass><langUsage><language ident="en"></language></langUsage></profileDesc><revisionDesc><change when="2019-12-20" who="#istex" xml:id="pub2tei">formatting</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/ark:/67375/WNG-DC82Q8J6-0/fulltext.txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component type="serialArticle" version="2.0" xml:id="jam5402" xml:lang="en"><header><publicationMeta level="product"><doi origin="wiley" registered="yes">10.1111/(ISSN)1365-2672</doi><issn type="print">1364-5072</issn><issn type="electronic">1365-2672</issn><idGroup><id type="product" value="JAM"></id></idGroup><titleGroup><title sort="JOURNAL OF APPLIED MICROBIOLOGY" type="main">Journal of Applied Microbiology</title><title type="short">J Appl Microbiol</title></titleGroup></publicationMeta><publicationMeta level="part" position="10104"><doi origin="wiley">10.1111/jam.2012.113.issue-4</doi><copyright ownership="thirdParty">Copyright © 2012 The Society for Applied Microbiology</copyright><numberingGroup><numbering type="journalVolume" number="113">113</numbering><numbering type="journalIssue">4</numbering></numberingGroup><coverDate startDate="2012-10">October 2012</coverDate></publicationMeta><publicationMeta level="unit" position="5" status="forIssue" type="article"><doi>10.1111/j.1365-2672.2012.05402.x</doi><idGroup><id type="unit" value="JAM5402"></id></idGroup><countGroup><count number="12" type="pageTotal"></count></countGroup><titleGroup><title type="articleCategory">Original Article</title><title type="tocHeading1">Original Articles</title><title type="tocHeading2">Biodefence</title></titleGroup><copyright ownership="thirdParty">© 2012 The Society for Applied Microbiology No claim to US Government works</copyright><eventGroup><event date="2012-02-22" type="manuscriptReceived"></event><event date="2012-07-13" type="manuscriptRevised"></event><event date="2012-07-16" type="manuscriptAccepted"></event><event agent="SPS" date="2012-07-27" type="xmlCreated"></event><event type="publishedOnlineAccepted" date="2012-07-19"></event><event type="publishedOnlineEarlyUnpaginated" date="2012-08-21"></event><event type="firstOnline" date="2012-08-21"></event><event type="publishedOnlineFinalForm" date="2012-09-12"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:4.0.1" date="2014-03-19"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.3.7 mode:FullText" date="2015-03-24"></event></eventGroup><numberingGroup><numbering type="pageFirst">767</numbering><numbering type="pageLast">778</numbering></numberingGroup><correspondenceTo><lineatedText><line>Correspondence</line><line>Joseph Wander, Air Force Research Laboratory, 139 Barnes Drive, Suite 2, Tyndall AFB, FL 32403. E‐mail: <email>joseph.wander@us.af.mil</email></line></lineatedText></correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:JAM.JAM5402.pdf"></link></linkGroup></publicationMeta><contentMeta><titleGroup><title type="main">Proportional mouse model for aerosol infection by influenza</title><title type="shortAuthors">R.S. McDonald <i>et al</i>.</title></titleGroup><creators><creator affiliationRef="#jam5402-aff-0001" creatorRole="author" xml:id="jam5402-cr-0001"><personName><givenNames>R.S.</givenNames> <familyName>McDonald</familyName></personName></creator><creator affiliationRef="#jam5402-aff-0002" creatorRole="author" xml:id="jam5402-cr-0002"><personName><givenNames>A.R.</givenNames> <familyName>Sambol</familyName></personName></creator><creator affiliationRef="#jam5402-aff-0001" creatorRole="author" xml:id="jam5402-cr-0003"><personName><givenNames>B.K.</givenNames> <familyName>Heimbuch</familyName></personName></creator><creator affiliationRef="#jam5402-aff-0002" creatorRole="author" xml:id="jam5402-cr-0004"><personName><givenNames>T.L.</givenNames> <familyName>Brown</familyName></personName></creator><creator affiliationRef="#jam5402-aff-0002" creatorRole="author" xml:id="jam5402-cr-0005"><personName><givenNames>S.H.</givenNames> <familyName>Hinrichs</familyName></personName></creator><creator affiliationRef="#jam5402-aff-0003" corresponding="yes" creatorRole="author" xml:id="jam5402-cr-0006"><personName><givenNames>J.D.</givenNames> <familyName>Wander</familyName></personName></creator></creators><affiliationGroup><affiliation countryCode="US" type="organization" xml:id="jam5402-aff-0001"><orgName>Applied Research Associates, Inc</orgName> <address><city>Panama City</city> <countryPart>FL</countryPart> <country>USA</country></address></affiliation><affiliation countryCode="US" type="organization" xml:id="jam5402-aff-0002"><orgName>University of Nebraska Medical Center, 985900 Nebraska Medical Center</orgName> <address><city>Omaha</city> <countryPart>NE</countryPart> <country>USA</country></address></affiliation><affiliation countryCode="US" type="organization" xml:id="jam5402-aff-0003"><orgDiv>Airbase Sciences Branch, Air Force Research Laboratory</orgDiv> <orgName>Tyndall AFB</orgName> <address><countryPart>FL</countryPart> <country>USA</country></address></affiliation></affiliationGroup><keywordGroup type="author"><keyword xml:id="jam5402-kwd-0001">aerosol</keyword><keyword xml:id="jam5402-kwd-0002"><fc>H</fc>1<fc>N</fc>1</keyword><keyword xml:id="jam5402-kwd-0003">infection</keyword><keyword xml:id="jam5402-kwd-0004">influenza</keyword><keyword xml:id="jam5402-kwd-0005">inhalation</keyword><keyword xml:id="jam5402-kwd-0006">mouse</keyword><keyword xml:id="jam5402-kwd-0007">respiratory protection</keyword></keywordGroup><fundingInfo><fundingAgency>Defence Threat Reduction Agency</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Biological Advanced Research and Development Authority (BARDA)</fundingAgency></fundingInfo><fundingInfo><fundingAgency>The Air Force Research Laboratory (AFRL)</fundingAgency></fundingInfo><abstractGroup><abstract type="main" xml:id="jam5402-abs-0001"><title type="main">Abstract</title><section xml:id="jam5402-sec-0001"><title type="main">Aims</title><p>The aim of this study was to demonstrate a prototype tool for measuring infectivity of an aerosolized human pathogen – influenza <fc>A</fc>/<fc>PR</fc>/8/34 (<fc>H</fc>1<fc>N</fc>1) virus – using a small‐animal model in the <fc>C</fc>ontrolled <fc>A</fc>erosol <fc>T</fc>est <fc>S</fc>ystem (<fc>CATS</fc>).</p></section><section xml:id="jam5402-sec-0002"><title type="main">Methods and Results</title><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><sub>50</sub> and ~12 <fc>TCID</fc><sub>50</sub>, respectively.</p></section><section xml:id="jam5402-sec-0003"><title type="main">Conclusions</title><p><fc>MID</fc><sub>50</sub> for inspired <fc>H</fc>1<fc>N</fc>1 aerosols in <fc>CD</fc>‐1 mice is between 12 and 40 <fc>TCID</fc><sub>50</sub>; proportionality to dose of weight loss and viral populations makes the <fc>CD</fc>‐1 mouse a useful model for measuring infectivity by inhalation.</p></section><section xml:id="jam5402-sec-0004"><title type="main">Significance and Impact of the Study</title><p>In the <fc>CATS</fc>, 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></section></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Proportional mouse model for aerosol infection by influenza</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Proportional mouse model for aerosol infection by influenza</title></titleInfo><name type="personal"><namePart type="given">R.S.</namePart><namePart type="family">McDonald</namePart><affiliation>Applied Research Associates, Inc, FL, Panama City, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">A.R.</namePart><namePart type="family">Sambol</namePart><affiliation>University of Nebraska Medical Center, 985900 Nebraska Medical Center, NE, Omaha, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">B.K.</namePart><namePart type="family">Heimbuch</namePart><affiliation>Applied Research Associates, Inc, FL, Panama City, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">T.L.</namePart><namePart type="family">Brown</namePart><affiliation>University of Nebraska Medical Center, 985900 Nebraska Medical Center, NE, Omaha, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">S.H.</namePart><namePart type="family">Hinrichs</namePart><affiliation>University of Nebraska Medical Center, 985900 Nebraska Medical Center, NE, Omaha, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">J.D.</namePart><namePart type="family">Wander</namePart><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><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><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></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><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. 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