Elevated Human Dipeptidyl Peptidase 4 Expression Reduces the Susceptibility of hDPP4 Transgenic Mice to Middle East Respiratory Syndrome Coronavirus Infection and Disease
Identifieur interne : 000991 ( Main/Exploration ); précédent : 000990; suivant : 000992Elevated Human Dipeptidyl Peptidase 4 Expression Reduces the Susceptibility of hDPP4 Transgenic Mice to Middle East Respiratory Syndrome Coronavirus Infection and Disease
Auteurs : Abdullah Algaissi [Arabie saoudite] ; Anurodh S. Agrawal ; Song Han ; Bi-Hung Peng ; Chuming Luo ; Fang Li ; Teh-Sheng Chan ; Robert B. Couch ; Chien-Te K. TsengSource :
- The Journal of Infectious Diseases [ 0022-1899 ] ; 2018.
Descripteurs français
- KwdFr :
- Animaux, Coronavirus du syndrome respiratoire du Moyen-Orient (croissance et développement), Dipeptidyl peptidase 4 (génétique), Dipeptidyl peptidase 4 (sang), Dose létale 50, Expression des gènes, Humains, Infections à coronavirus (immunologie), Infections à coronavirus (virologie), Modèles animaux de maladie humaine, Résistance à la maladie, Souris, Souris transgéniques.
- MESH :
- croissance et développement : Coronavirus du syndrome respiratoire du Moyen-Orient.
- génétique : Dipeptidyl peptidase 4.
- immunologie : Infections à coronavirus.
- sang : Dipeptidyl peptidase 4.
- virologie : Infections à coronavirus.
- Animaux, Dose létale 50, Expression des gènes, Humains, Modèles animaux de maladie humaine, Résistance à la maladie, Souris, Souris transgéniques.
English descriptors
- KwdEn :
- Animals, Coronavirus Infections (immunology), Coronavirus Infections (virology), Dipeptidyl Peptidase 4 (blood), Dipeptidyl Peptidase 4 (genetics), Disease Models, Animal, Disease Resistance, Gene Expression, Humans, Lethal Dose 50, Mice, Mice, Transgenic, Middle East Respiratory Syndrome Coronavirus (growth & development).
- MESH :
- chemical , blood : Dipeptidyl Peptidase 4.
- chemical , genetics : Dipeptidyl Peptidase 4.
- growth & development : Middle East Respiratory Syndrome Coronavirus.
- immunology : Coronavirus Infections.
- virology : Coronavirus Infections.
- Animals, Disease Models, Animal, Disease Resistance, Gene Expression, Humans, Lethal Dose 50, Mice, Mice, Transgenic.
Abstract
The ongoing Middle East respiratory syndrome coronavirus (MERS-CoV) infections pose threats to public health worldwide, making an understanding of MERS pathogenesis and development of effective medical countermeasures (MCMs) urgent.
We used homozygous (+/+) and heterozygous (+/−) human dipeptidyl peptidase 4 (hDPP4) transgenic mice to study the effect of hDPP4 on MERS-CoV infection. Specifically, we determined values of 50% lethal dose (LD50) of MERS-CoV for the 2 strains of mice, compared and correlated their levels of soluble (s)hDPP4 expression to susceptibility, and explored recombinant (r)shDPP4 as an effective MCM for MERS infection.
hDPP4+/+ mice were unexpectedly more resistant than hDPP4+/− mice to MERS-CoV infection, as judged by increased LD50, reduced lung viral infection, attenuated morbidity and mortality, and reduced histopathology. Additionally, the resistance to MERS-CoV infection directly correlated with increased serum shDPP4 and serum virus neutralizing activity. Finally, administration of rshDPP4 led to reduced lung virus titer and histopathology.
Our studies suggest that the serum shDPP4 levels play a role in MERS pathogenesis and demonstrate a potential of rshDPP4 as a treatment option for MERS. Additionally, it offers a validated pair of Tg mice strains for characterizing the effect of shDPP4 on MERS pathogenesis.
Url:
DOI: 10.1093/infdis/jiy574
PubMed: 30256968
PubMed Central: 6376904
Affiliations:
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Le document en format XML
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Tseng</name><affiliation><nlm:aff id="AF0001">Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston</nlm:aff><wicri:noCountry code="subfield">Galveston</wicri:noCountry></affiliation><affiliation><nlm:aff id="AF0005">Center for Biodefense and Emerging Infectious Disease, University of Texas Medical Branch, Galveston</nlm:aff><wicri:noCountry code="subfield">Galveston</wicri:noCountry></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">30256968</idno><idno type="pmc">6376904</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6376904</idno><idno type="RBID">PMC:6376904</idno><idno type="doi">10.1093/infdis/jiy574</idno><date when="2018">2018</date><idno type="wicri:Area/Pmc/Corpus">000E33</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000E33</idno><idno type="wicri:Area/Pmc/Curation">000E33</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000E33</idno><idno type="wicri:Area/Pmc/Checkpoint">000592</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000592</idno><idno type="wicri:source">PubMed</idno><idno type="RBID">pubmed:30256968</idno><idno type="wicri:Area/PubMed/Corpus">000770</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000770</idno><idno type="wicri:Area/PubMed/Curation">000770</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000770</idno><idno type="wicri:Area/PubMed/Checkpoint">000589</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000589</idno><idno type="wicri:Area/Ncbi/Merge">001F75</idno><idno type="wicri:Area/Ncbi/Curation">001F75</idno><idno type="wicri:Area/Ncbi/Checkpoint">001F75</idno><idno type="wicri:doubleKey">0022-1899:2018:Algaissi A:elevated:human:dipeptidyl</idno><idno type="wicri:Area/Main/Merge">000994</idno><idno type="wicri:Area/Main/Curation">000991</idno><idno type="wicri:Area/Main/Exploration">000991</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Elevated Human Dipeptidyl Peptidase 4 Expression Reduces the Susceptibility of hDPP4 Transgenic Mice to Middle East Respiratory Syndrome Coronavirus Infection and Disease</title><author><name sortKey="Algaissi, Abdullah" sort="Algaissi, Abdullah" uniqKey="Algaissi A" first="Abdullah" last="Algaissi">Abdullah Algaissi</name><affiliation><nlm:aff id="AF0001">Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston</nlm:aff><wicri:noCountry code="subfield">Galveston</wicri:noCountry></affiliation><affiliation wicri:level="1"><nlm:aff id="AF0007">Department of Medical Laboratories Technology, College of Applied Medical Sciences, Jazan University, Saudi Arabia</nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea>Department of Medical Laboratories Technology, College of Applied Medical Sciences, Jazan University</wicri:regionArea><wicri:noRegion>Jazan University</wicri:noRegion></affiliation></author><author><name sortKey="Agrawal, Anurodh S" sort="Agrawal, Anurodh S" uniqKey="Agrawal A" first="Anurodh S" last="Agrawal">Anurodh S. Agrawal</name><affiliation><nlm:aff id="AF0001">Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston</nlm:aff><wicri:noCountry code="subfield">Galveston</wicri:noCountry></affiliation></author><author><name sortKey="Han, Song" sort="Han, Song" uniqKey="Han S" first="Song" last="Han">Song Han</name><affiliation><nlm:aff id="AF0002">Department of Molecular Diagnostics, University of Texas Medical Branch, Galveston</nlm:aff><wicri:noCountry code="subfield">Galveston</wicri:noCountry></affiliation></author><author><name sortKey="Peng, Bi Hung" sort="Peng, Bi Hung" uniqKey="Peng B" first="Bi-Hung" last="Peng">Bi-Hung Peng</name><affiliation><nlm:aff id="AF0003">Department of Neurosciences, Cell Biology, and Anatomy, University of Texas Medical Branch, Galveston</nlm:aff><wicri:noCountry code="subfield">Galveston</wicri:noCountry></affiliation></author><author><name sortKey="Luo, Chuming" sort="Luo, Chuming" uniqKey="Luo C" first="Chuming" last="Luo">Chuming Luo</name><affiliation><nlm:aff id="AF0006">Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul</nlm:aff><wicri:noCountry code="subfield">Saint Paul</wicri:noCountry></affiliation></author><author><name sortKey="Li, Fang" sort="Li, Fang" uniqKey="Li F" first="Fang" last="Li">Fang Li</name><affiliation><nlm:aff id="AF0006">Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul</nlm:aff><wicri:noCountry code="subfield">Saint Paul</wicri:noCountry></affiliation></author><author><name sortKey="Chan, Teh Sheng" sort="Chan, Teh Sheng" uniqKey="Chan T" first="Teh-Sheng" last="Chan">Teh-Sheng Chan</name><affiliation><nlm:aff id="AF0001">Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston</nlm:aff><wicri:noCountry code="subfield">Galveston</wicri:noCountry></affiliation></author><author><name sortKey="Couch, Robert B" sort="Couch, Robert B" uniqKey="Couch R" first="Robert B" last="Couch">Robert B. Couch</name><affiliation><nlm:aff id="AF0004">Department of Internal Medicine, Division of Infectious Disease, University of Texas Medical Branch, Galveston</nlm:aff><wicri:noCountry code="subfield">Galveston</wicri:noCountry></affiliation></author><author><name sortKey="Tseng, Chien Te K" sort="Tseng, Chien Te K" uniqKey="Tseng C" first="Chien-Te K" last="Tseng">Chien-Te K. Tseng</name><affiliation><nlm:aff id="AF0001">Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston</nlm:aff><wicri:noCountry code="subfield">Galveston</wicri:noCountry></affiliation><affiliation><nlm:aff id="AF0005">Center for Biodefense and Emerging Infectious Disease, University of Texas Medical Branch, Galveston</nlm:aff><wicri:noCountry code="subfield">Galveston</wicri:noCountry></affiliation></author></analytic><series><title level="j">The Journal of Infectious Diseases</title><idno type="ISSN">0022-1899</idno><idno type="eISSN">1537-6613</idno><imprint><date when="2018">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Coronavirus Infections (immunology)</term><term>Coronavirus Infections (virology)</term><term>Dipeptidyl Peptidase 4 (blood)</term><term>Dipeptidyl Peptidase 4 (genetics)</term><term>Disease Models, Animal</term><term>Disease Resistance</term><term>Gene Expression</term><term>Humans</term><term>Lethal Dose 50</term><term>Mice</term><term>Mice, Transgenic</term><term>Middle East Respiratory Syndrome Coronavirus (growth & development)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (croissance et développement)</term><term>Dipeptidyl peptidase 4 (génétique)</term><term>Dipeptidyl peptidase 4 (sang)</term><term>Dose létale 50</term><term>Expression des gènes</term><term>Humains</term><term>Infections à coronavirus (immunologie)</term><term>Infections à coronavirus (virologie)</term><term>Modèles animaux de maladie humaine</term><term>Résistance à la maladie</term><term>Souris</term><term>Souris transgéniques</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Dipeptidyl Peptidase 4</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Dipeptidyl Peptidase 4</term></keywords><keywords scheme="MESH" qualifier="croissance et développement" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term></keywords><keywords scheme="MESH" qualifier="growth & development" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Dipeptidyl peptidase 4</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Infections à coronavirus</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Dipeptidyl peptidase 4</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Infections à coronavirus</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Disease Resistance</term><term>Gene Expression</term><term>Humans</term><term>Lethal Dose 50</term><term>Mice</term><term>Mice, Transgenic</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Dose létale 50</term><term>Expression des gènes</term><term>Humains</term><term>Modèles animaux de maladie humaine</term><term>Résistance à la maladie</term><term>Souris</term><term>Souris transgéniques</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Abstract</title><sec id="s1"><title>Background</title><p>The ongoing Middle East respiratory syndrome coronavirus (MERS-CoV) infections pose threats to public health worldwide, making an understanding of MERS pathogenesis and development of effective medical countermeasures (MCMs) urgent.</p></sec><sec id="s2"><title>Methods</title><p>We used homozygous (+/+) and heterozygous (+/−) human dipeptidyl peptidase 4 (hDPP4) transgenic mice to study the effect of hDPP4 on MERS-CoV infection. Specifically, we determined values of 50% lethal dose (LD<sub>50</sub>) of MERS-CoV for the 2 strains of mice, compared and correlated their levels of soluble (s)hDPP4 expression to susceptibility, and explored recombinant (r)shDPP4 as an effective MCM for MERS infection.</p></sec><sec id="s3"><title>Results</title><p>hDPP4<sup>+/+</sup> mice were unexpectedly more resistant than hDPP4<sup>+/−</sup> mice to MERS-CoV infection, as judged by increased LD<sub>50</sub>, reduced lung viral infection, attenuated morbidity and mortality, and reduced histopathology. Additionally, the resistance to MERS-CoV infection directly correlated with increased serum shDPP4 and serum virus neutralizing activity. Finally, administration of rshDPP4 led to reduced lung virus titer and histopathology.</p></sec><sec id="s4"><title>Conclusions</title><p>Our studies suggest that the serum shDPP4 levels play a role in MERS pathogenesis and demonstrate a potential of rshDPP4 as a treatment option for MERS. Additionally, it offers a validated pair of Tg mice strains for characterizing the effect of shDPP4 on MERS pathogenesis.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Raj, Vs" uniqKey="Raj V">VS Raj</name></author><author><name sortKey="Mou, H" uniqKey="Mou H">H Mou</name></author><author><name sortKey="Smits, Sl" uniqKey="Smits S">SL Smits</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Klemann, C" uniqKey="Klemann C">C Klemann</name></author><author><name sortKey="Wagner, L" uniqKey="Wagner L">L Wagner</name></author><author><name sortKey="Stephan, M" uniqKey="Stephan M">M Stephan</name></author><author><name sortKey="Von Horsten, S" uniqKey="Von Horsten S">S von Hörsten</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wagner, L" uniqKey="Wagner L">L Wagner</name></author><author><name sortKey="Klemann, C" uniqKey="Klemann C">C Klemann</name></author><author><name sortKey="Stephan, M" uniqKey="Stephan M">M Stephan</name></author><author><name sortKey="Von Horsten, S" uniqKey="Von Horsten S">S von Hörsten</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Agrawal, As" uniqKey="Agrawal A">AS Agrawal</name></author><author><name sortKey="Garron, T" uniqKey="Garron T">T Garron</name></author><author><name sortKey="Tao, X" uniqKey="Tao X">X Tao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tao, X" uniqKey="Tao X">X Tao</name></author><author><name sortKey="Garron, T" uniqKey="Garron T">T Garron</name></author><author><name sortKey="Agrawal, As" uniqKey="Agrawal A">AS Agrawal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Du, L" uniqKey="Du L">L Du</name></author><author><name sortKey="Kou, Z" uniqKey="Kou Z">Z Kou</name></author><author><name sortKey="Ma, C" uniqKey="Ma C">C 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sortKey="Geier, M" uniqKey="Geier M">M Geier</name></author><author><name sortKey="Marzi, A" uniqKey="Marzi A">A Marzi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huguenel, Ed" uniqKey="Huguenel E">ED Huguenel</name></author><author><name sortKey="Cohn, D" uniqKey="Cohn D">D Cohn</name></author><author><name sortKey="Dockum, Dp" uniqKey="Dockum D">DP Dockum</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gardner, Mr" uniqKey="Gardner M">MR Gardner</name></author><author><name sortKey="Kattenhorn, Lm" uniqKey="Kattenhorn L">LM Kattenhorn</name></author><author><name sortKey="Kondur, Hr" uniqKey="Kondur H">HR Kondur</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Saad, M" uniqKey="Saad M">M Saad</name></author><author><name sortKey="Omrani, As" uniqKey="Omrani A">AS Omrani</name></author><author><name sortKey="Baig, K" uniqKey="Baig K">K Baig</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arabi, Ym" uniqKey="Arabi Y">YM Arabi</name></author><author><name sortKey="Balkhy, Hh" uniqKey="Balkhy H">HH Balkhy</name></author><author><name sortKey="Hayden, Fg" uniqKey="Hayden F">FG Hayden</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Arabie saoudite</li></country></list><tree><noCountry><name sortKey="Agrawal, Anurodh S" sort="Agrawal, Anurodh S" uniqKey="Agrawal A" first="Anurodh S" last="Agrawal">Anurodh S. Agrawal</name><name sortKey="Chan, Teh Sheng" sort="Chan, Teh Sheng" uniqKey="Chan T" first="Teh-Sheng" last="Chan">Teh-Sheng Chan</name><name sortKey="Couch, Robert B" sort="Couch, Robert B" uniqKey="Couch R" first="Robert B" last="Couch">Robert B. Couch</name><name sortKey="Han, Song" sort="Han, Song" uniqKey="Han S" first="Song" last="Han">Song Han</name><name sortKey="Li, Fang" sort="Li, Fang" uniqKey="Li F" first="Fang" last="Li">Fang Li</name><name sortKey="Luo, Chuming" sort="Luo, Chuming" uniqKey="Luo C" first="Chuming" last="Luo">Chuming Luo</name><name sortKey="Peng, Bi Hung" sort="Peng, Bi Hung" uniqKey="Peng B" first="Bi-Hung" last="Peng">Bi-Hung Peng</name><name sortKey="Tseng, Chien Te K" sort="Tseng, Chien Te K" uniqKey="Tseng C" first="Chien-Te K" last="Tseng">Chien-Te K. Tseng</name></noCountry><country name="Arabie saoudite"><noRegion><name sortKey="Algaissi, Abdullah" sort="Algaissi, Abdullah" uniqKey="Algaissi A" first="Abdullah" last="Algaissi">Abdullah Algaissi</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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