MersV1, PubMed, Curation, bibRecord, 001326

Multi-Organ Damage in Human Dipeptidyl Peptidase 4 Transgenic Mice Infected with Middle East Respiratory Syndrome-Coronavirus.

Identifieur interne : 001326 ( PubMed/Curation ); précédent : 001325; suivant : 001327

Multi-Organ Damage in Human Dipeptidyl Peptidase 4 Transgenic Mice Infected with Middle East Respiratory Syndrome-Coronavirus.

Source :

PloS one [ 1932-6203 ] ; 2015.

RBID : pubmed:26701103

Descripteurs français

KwdFr :
- ARN messager (génétique), Animaux, Chimiokines (métabolisme), Coronavirus du syndrome respiratoire du Moyen-Orient (pathogénicité), Cytokines (métabolisme), Dipeptidyl peptidase 4 (physiologie), Défaillance multiviscérale (étiologie), Femelle, Humains, Infections à coronavirus (), Infections à coronavirus (virologie), RT-PCR, Réaction de polymérisation en chaine en temps réel, Souris, Souris de lignée C57BL, Souris transgéniques, Techniques immunoenzymatiques.
MESH :
- génétique : ARN messager.
- métabolisme : Chimiokines, Cytokines.
- pathogénicité : Coronavirus du syndrome respiratoire du Moyen-Orient.
- physiologie : Dipeptidyl peptidase 4.
- virologie : Infections à coronavirus.
- étiologie : Défaillance multiviscérale.
- Animaux, Femelle, Humains, Infections à coronavirus, RT-PCR, Réaction de polymérisation en chaine en temps réel, Souris, Souris de lignée C57BL, Souris transgéniques, Techniques immunoenzymatiques.

English descriptors

KwdEn :
- Animals, Chemokines (metabolism), Coronavirus Infections (complications), Coronavirus Infections (virology), Cytokines (metabolism), Dipeptidyl Peptidase 4 (physiology), Female, Humans, Immunoenzyme Techniques, Mice, Mice, Inbred C57BL, Mice, Transgenic, Middle East Respiratory Syndrome Coronavirus (pathogenicity), Multiple Organ Failure (etiology), RNA, Messenger (genetics), Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction.
MESH :
- chemical , genetics : RNA, Messenger.
- chemical , metabolism : Chemokines, Cytokines.
- complications : Coronavirus Infections.
- etiology : Multiple Organ Failure.
- pathogenicity : Middle East Respiratory Syndrome Coronavirus.
- chemical , physiology : Dipeptidyl Peptidase 4.
- virology : Coronavirus Infections.
- Animals, Female, Humans, Immunoenzyme Techniques, Mice, Mice, Inbred C57BL, Mice, Transgenic, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction.

Abstract

The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe acute respiratory failure and considerable extrapumonary organ dysfuction with substantial high mortality. For the limited number of autopsy reports, small animal models are urgently needed to study the mechanisms of MERS-CoV infection and pathogenesis of the disease and to evaluate the efficacy of therapeutics against MERS-CoV infection. In this study, we developed a transgenic mouse model globally expressing codon-optimized human dipeptidyl peptidase 4 (hDPP4), the receptor for MERS-CoV. After intranasal inoculation with MERS-CoV, the mice rapidly developed severe pneumonia and multi-organ damage, with viral replication being detected in the lungs on day 5 and in the lungs, kidneys and brains on day 9 post-infection. In addition, the mice exhibited systemic inflammation with mild to severe pneumonia accompanied by the injury of liver, kidney and spleen with neutrophil and macrophage infiltration. Importantly, the mice exhibited symptoms of paralysis with high viral burden and viral positive neurons on day 9. Taken together, this study characterizes the tropism of MERS-CoV upon infection. Importantly, this hDPP4-expressing transgenic mouse model will be applicable for studying the pathogenesis of MERS-CoV infection and investigating the efficacy of vaccines and antiviral agents designed to combat MERS-CoV infection.

DOI: 10.1371/journal.pone.0145561
PubMed: 26701103

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<author><name sortKey="Du, Lanying" sort="Du, Lanying" uniqKey="Du L" first="Lanying" last="Du">Lanying Du</name>
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<author><name sortKey="Tan, Wenjie" sort="Tan, Wenjie" uniqKey="Tan W" first="Wenjie" last="Tan">Wenjie Tan</name>
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<author><name sortKey="Zhou, Yusen" sort="Zhou, Yusen" uniqKey="Zhou Y" first="Yusen" last="Zhou">Yusen Zhou</name>
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<author><name sortKey="Jiang, Yuting" sort="Jiang, Yuting" uniqKey="Jiang Y" first="Yuting" last="Jiang">Yuting Jiang</name>
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<author><name sortKey="Kou, Zhihua" sort="Kou, Zhihua" uniqKey="Kou Z" first="Zhihua" last="Kou">Zhihua Kou</name>
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<country xml:lang="fr">République populaire de Chine</country>
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<author><name sortKey="Du, Lanying" sort="Du, Lanying" uniqKey="Du L" first="Lanying" last="Du">Lanying Du</name>
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<country xml:lang="fr">États-Unis</country>
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<author><name sortKey="Tan, Wenjie" sort="Tan, Wenjie" uniqKey="Tan W" first="Wenjie" last="Tan">Wenjie Tan</name>
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<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, 102206</wicri:regionArea>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, 10065</wicri:regionArea>
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<author><name sortKey="Sun, Shihui" sort="Sun, Shihui" uniqKey="Sun S" first="Shihui" last="Sun">Shihui Sun</name>
<affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071</wicri:regionArea>
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<author><name sortKey="Zhou, Yusen" sort="Zhou, Yusen" uniqKey="Zhou Y" first="Yusen" last="Zhou">Yusen Zhou</name>
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<country xml:lang="fr">République populaire de Chine</country>
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<term>Chemokines (metabolism)</term>
<term>Coronavirus Infections (complications)</term>
<term>Coronavirus Infections (virology)</term>
<term>Cytokines (metabolism)</term>
<term>Dipeptidyl Peptidase 4 (physiology)</term>
<term>Female</term>
<term>Humans</term>
<term>Immunoenzyme Techniques</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Mice, Transgenic</term>
<term>Middle East Respiratory Syndrome Coronavirus (pathogenicity)</term>
<term>Multiple Organ Failure (etiology)</term>
<term>RNA, Messenger (genetics)</term>
<term>Real-Time Polymerase Chain Reaction</term>
<term>Reverse Transcriptase Polymerase Chain Reaction</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>ARN messager (génétique)</term>
<term>Animaux</term>
<term>Chimiokines (métabolisme)</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient (pathogénicité)</term>
<term>Cytokines (métabolisme)</term>
<term>Dipeptidyl peptidase 4 (physiologie)</term>
<term>Défaillance multiviscérale (étiologie)</term>
<term>Femelle</term>
<term>Humains</term>
<term>Infections à coronavirus ()</term>
<term>Infections à coronavirus (virologie)</term>
<term>RT-PCR</term>
<term>Réaction de polymérisation en chaine en temps réel</term>
<term>Souris</term>
<term>Souris de lignée C57BL</term>
<term>Souris transgéniques</term>
<term>Techniques immunoenzymatiques</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>RNA, Messenger</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Chemokines</term>
<term>Cytokines</term>
</keywords>
<keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Coronavirus Infections</term>
</keywords>
<keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Multiple Organ Failure</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>ARN messager</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Chimiokines</term>
<term>Cytokines</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Dipeptidyl peptidase 4</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><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" qualifier="étiologie" xml:lang="fr"><term>Défaillance multiviscérale</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Female</term>
<term>Humans</term>
<term>Immunoenzyme Techniques</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Mice, Transgenic</term>
<term>Real-Time Polymerase Chain Reaction</term>
<term>Reverse Transcriptase Polymerase Chain Reaction</term>
</keywords>
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<term>Femelle</term>
<term>Humains</term>
<term>Infections à coronavirus</term>
<term>RT-PCR</term>
<term>Réaction de polymérisation en chaine en temps réel</term>
<term>Souris</term>
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<front><div type="abstract" xml:lang="en">The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe acute respiratory failure and considerable extrapumonary organ dysfuction with substantial high mortality. For the limited number of autopsy reports, small animal models are urgently needed to study the mechanisms of MERS-CoV infection and pathogenesis of the disease and to evaluate the efficacy of therapeutics against MERS-CoV infection. In this study, we developed a transgenic mouse model globally expressing codon-optimized human dipeptidyl peptidase 4 (hDPP4), the receptor for MERS-CoV. After intranasal inoculation with MERS-CoV, the mice rapidly developed severe pneumonia and multi-organ damage, with viral replication being detected in the lungs on day 5 and in the lungs, kidneys and brains on day 9 post-infection. In addition, the mice exhibited systemic inflammation with mild to severe pneumonia accompanied by the injury of liver, kidney and spleen with neutrophil and macrophage infiltration. Importantly, the mice exhibited symptoms of paralysis with high viral burden and viral positive neurons on day 9. Taken together, this study characterizes the tropism of MERS-CoV upon infection. Importantly, this hDPP4-expressing transgenic mouse model will be applicable for studying the pathogenesis of MERS-CoV infection and investigating the efficacy of vaccines and antiviral agents designed to combat MERS-CoV infection. </div>
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<DateCompleted><Year>2016</Year>
<Month>08</Month>
<Day>17</Day>
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<DateRevised><Year>2019</Year>
<Month>02</Month>
<Day>22</Day>
</DateRevised>
<Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Electronic">1932-6203</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>10</Volume>
<Issue>12</Issue>
<PubDate><Year>2015</Year>
</PubDate>
</JournalIssue>
<Title>PloS one</Title>
<ISOAbbreviation>PLoS ONE</ISOAbbreviation>
</Journal>
<ArticleTitle>Multi-Organ Damage in Human Dipeptidyl Peptidase 4 Transgenic Mice Infected with Middle East Respiratory Syndrome-Coronavirus.</ArticleTitle>
<Pagination><MedlinePgn>e0145561</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1371/journal.pone.0145561</ELocationID>
<Abstract><AbstractText>The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe acute respiratory failure and considerable extrapumonary organ dysfuction with substantial high mortality. For the limited number of autopsy reports, small animal models are urgently needed to study the mechanisms of MERS-CoV infection and pathogenesis of the disease and to evaluate the efficacy of therapeutics against MERS-CoV infection. In this study, we developed a transgenic mouse model globally expressing codon-optimized human dipeptidyl peptidase 4 (hDPP4), the receptor for MERS-CoV. After intranasal inoculation with MERS-CoV, the mice rapidly developed severe pneumonia and multi-organ damage, with viral replication being detected in the lungs on day 5 and in the lungs, kidneys and brains on day 9 post-infection. In addition, the mice exhibited systemic inflammation with mild to severe pneumonia accompanied by the injury of liver, kidney and spleen with neutrophil and macrophage infiltration. Importantly, the mice exhibited symptoms of paralysis with high viral burden and viral positive neurons on day 9. Taken together, this study characterizes the tropism of MERS-CoV upon infection. Importantly, this hDPP4-expressing transgenic mouse model will be applicable for studying the pathogenesis of MERS-CoV infection and investigating the efficacy of vaccines and antiviral agents designed to combat MERS-CoV infection. </AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Zhao</LastName>
<ForeName>Guangyu</ForeName>
<Initials>G</Initials>
<AffiliationInfo><Affiliation>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Jiang</LastName>
<ForeName>Yuting</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Qiu</LastName>
<ForeName>Hongjie</ForeName>
<Initials>H</Initials>
<AffiliationInfo><Affiliation>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Gao</LastName>
<ForeName>Tongtong</ForeName>
<Initials>T</Initials>
<AffiliationInfo><Affiliation>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zeng</LastName>
<ForeName>Yang</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Guo</LastName>
<ForeName>Yan</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Yu</LastName>
<ForeName>Hong</ForeName>
<Initials>H</Initials>
<AffiliationInfo><Affiliation>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Li</LastName>
<ForeName>Junfeng</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kou</LastName>
<ForeName>Zhihua</ForeName>
<Initials>Z</Initials>
<AffiliationInfo><Affiliation>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Du</LastName>
<ForeName>Lanying</ForeName>
<Initials>L</Initials>
<AffiliationInfo><Affiliation>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, 10065, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Tan</LastName>
<ForeName>Wenjie</ForeName>
<Initials>W</Initials>
<AffiliationInfo><Affiliation>Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, 102206, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Jiang</LastName>
<ForeName>Shibo</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, 10065, United States of America.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College, Fudan University, Shanghai, 200433, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Sun</LastName>
<ForeName>Shihui</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zhou</LastName>
<ForeName>Yusen</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2015</Year>
<Month>12</Month>
<Day>23</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>PLoS One</MedlineTA>
<NlmUniqueID>101285081</NlmUniqueID>
<ISSNLinking>1932-6203</ISSNLinking>
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<NameOfSubstance UI="D018925">Chemokines</NameOfSubstance>
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<Chemical><RegistryNumber>0</RegistryNumber>
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<Chemical><RegistryNumber>EC 3.4.14.5</RegistryNumber>
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<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
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<MeshHeading><DescriptorName UI="D018819" MajorTopicYN="N">Dipeptidyl Peptidase 4</DescriptorName>
<QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D007124" MajorTopicYN="N">Immunoenzyme Techniques</DescriptorName>
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<MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008810" MajorTopicYN="N">Mice, Inbred C57BL</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008822" MajorTopicYN="N">Mice, Transgenic</DescriptorName>
</MeshHeading>
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Multi-Organ Damage in Human Dipeptidyl Peptidase 4 Transgenic Mice Infected with Middle East Respiratory Syndrome-Coronavirus.

Multi-Organ Damage in Human Dipeptidyl Peptidase 4 Transgenic Mice Infected with Middle East Respiratory Syndrome-Coronavirus.

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