Elevated Human Dipeptidyl Peptidase 4 Expression Reduces the Susceptibility of hDPP4 Transgenic Mice to Middle East Respiratory Syndrome Coronavirus Infection and Disease
Identifieur interne : 000E33 ( Pmc/Curation ); précédent : 000E32; suivant : 000E34Elevated 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.
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
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Abdullah Algaissi<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>
</affiliation>
<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="AF0002">Department of Molecular Diagnostics, University of Texas Medical Branch, Galveston</nlm:aff>
<wicri:noCountry code="subfield">Galveston</wicri:noCountry>
</affiliation>
<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>
<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>
<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>
<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="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>
<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>
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<affiliation><nlm:aff id="AF0005">Center for Biodefense and Emerging Infectious Disease, University of Texas Medical Branch, Galveston</nlm:aff>
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<wicri:noCountry code="subfield">Galveston</wicri:noCountry>
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<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>
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<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>
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<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>
</affiliation>
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<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>
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<author><name sortKey="Han, Song" sort="Han, Song" uniqKey="Han S" first="Song" last="Han">Song Han</name>
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<wicri:noCountry code="subfield">Galveston</wicri:noCountry>
</affiliation>
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<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>
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<author><name sortKey="Li, Fang" sort="Li, Fang" uniqKey="Li F" first="Fang" last="Li">Fang Li</name>
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<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>
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<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>
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<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>
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<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 Ma</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Yang, Y" uniqKey="Yang Y">Y Yang</name>
</author>
<author><name sortKey="Du, L" uniqKey="Du L">L Du</name>
</author>
<author><name sortKey="Liu, C" uniqKey="Liu C">C Liu</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lu, G" uniqKey="Lu G">G Lu</name>
</author>
<author><name sortKey="Hu, Y" uniqKey="Hu Y">Y Hu</name>
</author>
<author><name sortKey="Wang, Q" uniqKey="Wang Q">Q Wang</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mamgain, S" uniqKey="Mamgain S">S Mamgain</name>
</author>
<author><name sortKey="Mathur, S" uniqKey="Mathur S">S Mathur</name>
</author>
<author><name sortKey="Kothiyal, P" uniqKey="Kothiyal P">P Kothiyal</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lambeir, Am" uniqKey="Lambeir A">AM Lambeir</name>
</author>
<author><name sortKey="Durinx, C" uniqKey="Durinx C">C Durinx</name>
</author>
<author><name sortKey="Scharpe, S" uniqKey="Scharpe S">S Scharpé</name>
</author>
<author><name sortKey="De Meester, I" uniqKey="De Meester I">I De Meester</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Agrawal, As" uniqKey="Agrawal A">AS Agrawal</name>
</author>
<author><name sortKey="Tao, X" uniqKey="Tao X">X Tao</name>
</author>
<author><name sortKey="Algaissi, A" uniqKey="Algaissi A">A Algaissi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Morimoto, C" uniqKey="Morimoto C">C Morimoto</name>
</author>
<author><name sortKey="Schlossman, Sf" uniqKey="Schlossman S">SF Schlossman</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Nohtomi, K" uniqKey="Nohtomi K">K Nohtomi</name>
</author>
<author><name sortKey="Terasaki, M" uniqKey="Terasaki M">M Terasaki</name>
</author>
<author><name sortKey="Kohashi, K" uniqKey="Kohashi K">K Kohashi</name>
</author>
<author><name sortKey="Hiromura, M" uniqKey="Hiromura M">M Hiromura</name>
</author>
<author><name sortKey="Nagashima, M" uniqKey="Nagashima M">M Nagashima</name>
</author>
<author><name sortKey="Hirano, T" uniqKey="Hirano T">T Hirano</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Itou, M" uniqKey="Itou M">M Itou</name>
</author>
<author><name sortKey="Kawaguchi, T" uniqKey="Kawaguchi T">T Kawaguchi</name>
</author>
<author><name sortKey="Taniguchi, E" uniqKey="Taniguchi E">E Taniguchi</name>
</author>
<author><name sortKey="Sata, M" uniqKey="Sata M">M Sata</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Inn, Ks" uniqKey="Inn K">KS Inn</name>
</author>
<author><name sortKey="Kim, Y" uniqKey="Kim Y">Y Kim</name>
</author>
<author><name sortKey="Aigerim, A" uniqKey="Aigerim A">A Aigerim</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hofmann, H" uniqKey="Hofmann H">H Hofmann</name>
</author>
<author><name 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>
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<front><journal-meta><journal-id journal-id-type="nlm-ta">J Infect Dis</journal-id>
<journal-id journal-id-type="iso-abbrev">J. Infect. Dis</journal-id>
<journal-id journal-id-type="publisher-id">jid</journal-id>
<journal-title-group><journal-title>The Journal of Infectious Diseases</journal-title>
</journal-title-group>
<issn pub-type="ppub">0022-1899</issn>
<issn pub-type="epub">1537-6613</issn>
<publisher><publisher-name>Oxford University Press</publisher-name>
<publisher-loc>US</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">30256968</article-id>
<article-id pub-id-type="pmc">6376904</article-id>
<article-id pub-id-type="doi">10.1093/infdis/jiy574</article-id>
<article-id pub-id-type="publisher-id">jiy574</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Major Articles and Brief Reports</subject>
<subj-group subj-group-type="category-toc-heading"><subject>Pathogenesis and Host Response</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group><article-title>Elevated Human Dipeptidyl Peptidase 4 Expression Reduces the Susceptibility of hDPP4 Transgenic Mice to Middle East Respiratory Syndrome Coronavirus Infection and Disease</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Algaissi</surname>
<given-names>Abdullah</given-names>
</name>
<xref ref-type="aff" rid="AF0001">1</xref>
<xref ref-type="aff" rid="AF0007">7</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Agrawal</surname>
<given-names>Anurodh S</given-names>
</name>
<xref ref-type="aff" rid="AF0001">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Han</surname>
<given-names>Song</given-names>
</name>
<xref ref-type="aff" rid="AF0002">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Peng</surname>
<given-names>Bi-Hung</given-names>
</name>
<xref ref-type="aff" rid="AF0003">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Luo</surname>
<given-names>Chuming</given-names>
</name>
<xref ref-type="aff" rid="AF0006">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Li</surname>
<given-names>Fang</given-names>
</name>
<xref ref-type="aff" rid="AF0006">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chan</surname>
<given-names>Teh-Sheng</given-names>
</name>
<xref ref-type="aff" rid="AF0001">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Couch</surname>
<given-names>Robert B</given-names>
</name>
<xref ref-type="aff" rid="AF0004">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Tseng</surname>
<given-names>Chien-Te K</given-names>
</name>
<xref ref-type="aff" rid="AF0001">1</xref>
<xref ref-type="aff" rid="AF0005">5</xref>
<xref ref-type="corresp" rid="c1"></xref>
<pmc-comment>sktseng@utmb.edu </pmc-comment>
</contrib>
</contrib-group>
<aff id="AF0001"><label>1</label>
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston</aff>
<aff id="AF0002"><label>2</label>
Department of Molecular Diagnostics, University of Texas Medical Branch, Galveston</aff>
<aff id="AF0003"><label>3</label>
Department of Neurosciences, Cell Biology, and Anatomy, University of Texas Medical Branch, Galveston</aff>
<aff id="AF0004"><label>4</label>
Department of Internal Medicine, Division of Infectious Disease, University of Texas Medical Branch, Galveston</aff>
<aff id="AF0005"><label>5</label>
Center for Biodefense and Emerging Infectious Disease, University of Texas Medical Branch, Galveston</aff>
<aff id="AF0006"><label>6</label>
Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul</aff>
<aff id="AF0007"><label>7</label>
Department of Medical Laboratories Technology, College of Applied Medical Sciences, Jazan University, Saudi Arabia</aff>
<author-notes><corresp id="c1">Correspondence: Chien-Te K. Tseng, PhD, Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Boulevard, Galveston National Laboratory 5.200Q, Galveston, TX 77555-0609 (<email>sktseng@utmb.edu</email>
).</corresp>
</author-notes>
<pub-date pub-type="ppub"><day>01</day>
<month>3</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="epub" iso-8601-date="2018-09-26"><day>26</day>
<month>9</month>
<year>2018</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>15</day>
<month>2</month>
<year>2020</year>
</pub-date>
<pmc-comment> PMC Release delay is 12 months and
0 days and was based on the . </pmc-comment>
<volume>219</volume>
<issue>5</issue>
<fpage>829</fpage>
<lpage>835</lpage>
<history><date date-type="received"><day>09</day>
<month>8</month>
<year>2018</year>
</date>
<date date-type="accepted"><day>20</day>
<month>9</month>
<year>2018</year>
</date>
</history>
<permissions><copyright-statement>© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.</copyright-statement>
<copyright-year>2018</copyright-year>
<license license-type="oup-standard" xlink:href="https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model"><license-p>This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (<ext-link ext-link-type="uri" xlink:href="https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model">https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model</ext-link>
)</license-p>
</license>
<license><license-p>This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.</license-p>
</license>
</permissions>
<self-uri xlink:href="jiy574.pdf"></self-uri>
<abstract><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>
</abstract>
<abstract abstract-type="teaser"><p>We demonstrated that elevated levels of circulating soluble human (sh)DPP4 positively correlated with the resistance to MERS-CoV infection and identified the potential of recombinant shDPP4 as a treatment option for MERS.</p>
</abstract>
<kwd-group><kwd>Middle East respiratory syndrome coronavirus</kwd>
<kwd>MERS pathogenesis</kwd>
<kwd>human DPP4</kwd>
<kwd>transgenic mice</kwd>
<kwd>medical countermeasures for MERS</kwd>
</kwd-group>
<funding-group><award-group award-type="grant"><funding-source><named-content content-type="funder-name">National Institute of Allergy and Infectious Diseases</named-content>
<named-content content-type="funder-identifier">10.13039/100000060</named-content>
</funding-source>
</award-group>
<award-group award-type="grant"><funding-source><named-content content-type="funder-name">National Institutes of Health</named-content>
<named-content content-type="funder-identifier">10.13039/100000002</named-content>
</funding-source>
<award-id>R21AI113206</award-id>
<award-id>R01AI110700</award-id>
</award-group>
</funding-group>
<counts><page-count count="7"></page-count>
</counts>
</article-meta>
</front>
</pmc>
</record>
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