A Human DPP4-Knockin Mouse’s Susceptibility to Infection by Authentic and Pseudotyped MERS-CoV
Identifieur interne : 000A95 ( Main/Exploration ); précédent : 000A94; suivant : 000A96A Human DPP4-Knockin Mouse’s Susceptibility to Infection by Authentic and Pseudotyped MERS-CoV
Auteurs : Changfa Fan ; Xi Wu ; Qiang Liu ; Qianqian Li ; Susu Liu ; Jianjun Lu ; Yanwei Yang ; Yuan Cao ; Weijin Huang ; Chunnan Liang ; Tianlei Ying ; Shibo Jiang ; Youchun WangSource :
- Viruses [ 1999-4915 ] ; 2018.
Descripteurs français
- KwdFr :
- Animaux, Anticorps antiviraux (administration et posologie), Anticorps neutralisants (administration et posologie), Clustered regularly interspaced short palindromic repeats, Coronavirus du syndrome respiratoire du Moyen-Orient (croissance et développement), Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie), Dipeptidyl peptidase 4 (génétique), Dipeptidyl peptidase 4 (métabolisme), Endonucleases (métabolisme), Humains, Infections à coronavirus (), Infections à coronavirus (immunologie), Infections à coronavirus (virologie), Modèles animaux de maladie humaine, Protéines bactériennes (métabolisme), Recombinaison génétique, Souris, Susceptibilité à une maladie, Techniques de knock-in de gènes.
- MESH :
- administration et posologie : Anticorps antiviraux, Anticorps neutralisants.
- croissance et développement : Coronavirus du syndrome respiratoire du Moyen-Orient.
- génétique : Dipeptidyl peptidase 4.
- immunologie : Coronavirus du syndrome respiratoire du Moyen-Orient, Infections à coronavirus.
- métabolisme : Dipeptidyl peptidase 4, Endonucleases, Protéines bactériennes.
- virologie : Infections à coronavirus.
- Animaux, Clustered regularly interspaced short palindromic repeats, Humains, Infections à coronavirus, Modèles animaux de maladie humaine, Recombinaison génétique, Souris, Susceptibilité à une maladie, Techniques de knock-in de gènes.
English descriptors
- KwdEn :
- Animals, Antibodies, Neutralizing (administration & dosage), Antibodies, Viral (administration & dosage), Bacterial Proteins (metabolism), CRISPR-Associated Protein 9, Clustered Regularly Interspaced Short Palindromic Repeats, Coronavirus Infections (immunology), Coronavirus Infections (prevention & control), Coronavirus Infections (virology), Dipeptidyl Peptidase 4 (genetics), Dipeptidyl Peptidase 4 (metabolism), Disease Models, Animal, Disease Susceptibility, Endonucleases (metabolism), Gene Knock-In Techniques, Humans, Mice, Middle East Respiratory Syndrome Coronavirus (growth & development), Middle East Respiratory Syndrome Coronavirus (immunology), Recombination, Genetic.
- MESH :
- chemical , administration & dosage : Antibodies, Neutralizing, Antibodies, Viral.
- chemical , genetics : Dipeptidyl Peptidase 4.
- chemical , metabolism : Bacterial Proteins, Dipeptidyl Peptidase 4, Endonucleases.
- growth & development : Middle East Respiratory Syndrome Coronavirus.
- immunology : Coronavirus Infections, Middle East Respiratory Syndrome Coronavirus.
- prevention & control : Coronavirus Infections.
- virology : Coronavirus Infections.
- Animals, CRISPR-Associated Protein 9, Clustered Regularly Interspaced Short Palindromic Repeats, Disease Models, Animal, Disease Susceptibility, Gene Knock-In Techniques, Humans, Mice, Recombination, Genetic.
Abstract
Infection by the Middle East respiratory syndrome coronavirus (MERS-CoV) causes respiratory illness and has a high mortality rate (~35%). The requirement for the virus to be manipulated in a biosafety level three (BSL-3) facility has impeded development of urgently-needed antiviral agents. Here, we established anovel mouse model by inserting human dipeptidyl peptidase 4 (hDPP4) into the Rosa26 locus using CRISPR/Cas9, resulting in global expression of the transgene in a genetically stable mouse line. The mice were highly susceptible to infection by MERS-CoV clinical strain hCoV-EMC, which induced severe diffuse pulmonary disease in the animals, and could also be infected by an optimized pseudotyped MERS-CoV. Administration of the neutralizing monoclonal antibodies, H111-1 and m336, as well as a fusion inhibitor peptide, HR2P-M2, protected mice from challenge with authentic and pseudotyped MERS-CoV. These results confirmed that the hDPP4-knockin mouse is a novel model for studies of MERS-CoV pathogenesis and anti-MERS-CoV antiviral agents in BSL-3 and BSL-2facilities, respectively.
Url:
DOI: 10.3390/v10090448
PubMed: 30142928
PubMed Central: 6164841
Affiliations:
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Le document en format XML
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<author><name sortKey="Fan, Changfa" sort="Fan, Changfa" uniqKey="Fan C" first="Changfa" last="Fan">Changfa Fan</name>
<affiliation><nlm:aff id="af1-viruses-10-00448">Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, Beijing 100050, China;<email>fancf@nifdc.org.cn</email>
(C.F.);<email>wuxi@nifdc.org.cn</email>
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<author><name sortKey="Wu, Xi" sort="Wu, Xi" uniqKey="Wu X" first="Xi" last="Wu">Xi Wu</name>
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<author><name sortKey="Liu, Qiang" sort="Liu, Qiang" uniqKey="Liu Q" first="Qiang" last="Liu">Qiang Liu</name>
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<author><name sortKey="Li, Qianqian" sort="Li, Qianqian" uniqKey="Li Q" first="Qianqian" last="Li">Qianqian Li</name>
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<author><name sortKey="Liu, Susu" sort="Liu, Susu" uniqKey="Liu S" first="Susu" last="Liu">Susu Liu</name>
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<author><name sortKey="Lu, Jianjun" sort="Lu, Jianjun" uniqKey="Lu J" first="Jianjun" last="Lu">Jianjun Lu</name>
<affiliation><nlm:aff id="af3-viruses-10-00448">National Center for Safety Evaluation of Drugs, Institute for Food and Drug Safety Evaluation, National Institutes for Food and Drug Control, A8 Hongda Middle Street, Beijing Economic-Technological Development Area, Beijing 100176, China;<email>lujianjun@nifdc.org.cn</email>
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<author><name sortKey="Yang, Yanwei" sort="Yang, Yanwei" uniqKey="Yang Y" first="Yanwei" last="Yang">Yanwei Yang</name>
<affiliation><nlm:aff id="af3-viruses-10-00448">National Center for Safety Evaluation of Drugs, Institute for Food and Drug Safety Evaluation, National Institutes for Food and Drug Control, A8 Hongda Middle Street, Beijing Economic-Technological Development Area, Beijing 100176, China;<email>lujianjun@nifdc.org.cn</email>
(J.L.);<email>yangyanwei@nifdc.org.cn</email>
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<author><name sortKey="Cao, Yuan" sort="Cao, Yuan" uniqKey="Cao Y" first="Yuan" last="Cao">Yuan Cao</name>
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<author><name sortKey="Huang, Weijin" sort="Huang, Weijin" uniqKey="Huang W" first="Weijin" last="Huang">Weijin Huang</name>
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(Q.L.);<email>liqianqian1199@163.com</email>
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(T.Y.);<email>shibojiang@fudan.edu.cn</email>
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(T.Y.);<email>shibojiang@fudan.edu.cn</email>
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<author><name sortKey="Wang, Youchun" sort="Wang, Youchun" uniqKey="Wang Y" first="Youchun" last="Wang">Youchun Wang</name>
<affiliation><nlm:aff id="af2-viruses-10-00448">Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, National Institutes for Food and Drug Control, Beijing 100050, China;<email>liuqiang@nifdc.org.cn</email>
(Q.L.);<email>liqianqian1199@163.com</email>
(Q.L.);<email>huangweijin@nifdc.org.cn</email>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A Human DPP4-Knockin Mouse’s Susceptibility to Infection by Authentic and Pseudotyped MERS-CoV</title>
<author><name sortKey="Fan, Changfa" sort="Fan, Changfa" uniqKey="Fan C" first="Changfa" last="Fan">Changfa Fan</name>
<affiliation><nlm:aff id="af1-viruses-10-00448">Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, Beijing 100050, China;<email>fancf@nifdc.org.cn</email>
(C.F.);<email>wuxi@nifdc.org.cn</email>
(X.W.);<email>liususu@nifdc.org.cn</email>
(S.L.);<email>caoyuan0512@163.com</email>
(Y.C.);<email>chunnan_liang@nifdc.org.cn</email>
(C.L.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wu, Xi" sort="Wu, Xi" uniqKey="Wu X" first="Xi" last="Wu">Xi Wu</name>
<affiliation><nlm:aff id="af1-viruses-10-00448">Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, Beijing 100050, China;<email>fancf@nifdc.org.cn</email>
(C.F.);<email>wuxi@nifdc.org.cn</email>
(X.W.);<email>liususu@nifdc.org.cn</email>
(S.L.);<email>caoyuan0512@163.com</email>
(Y.C.);<email>chunnan_liang@nifdc.org.cn</email>
(C.L.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Liu, Qiang" sort="Liu, Qiang" uniqKey="Liu Q" first="Qiang" last="Liu">Qiang Liu</name>
<affiliation><nlm:aff id="af2-viruses-10-00448">Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, National Institutes for Food and Drug Control, Beijing 100050, China;<email>liuqiang@nifdc.org.cn</email>
(Q.L.);<email>liqianqian1199@163.com</email>
(Q.L.);<email>huangweijin@nifdc.org.cn</email>
(W.H.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Li, Qianqian" sort="Li, Qianqian" uniqKey="Li Q" first="Qianqian" last="Li">Qianqian Li</name>
<affiliation><nlm:aff id="af2-viruses-10-00448">Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, National Institutes for Food and Drug Control, Beijing 100050, China;<email>liuqiang@nifdc.org.cn</email>
(Q.L.);<email>liqianqian1199@163.com</email>
(Q.L.);<email>huangweijin@nifdc.org.cn</email>
(W.H.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Liu, Susu" sort="Liu, Susu" uniqKey="Liu S" first="Susu" last="Liu">Susu Liu</name>
<affiliation><nlm:aff id="af1-viruses-10-00448">Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, Beijing 100050, China;<email>fancf@nifdc.org.cn</email>
(C.F.);<email>wuxi@nifdc.org.cn</email>
(X.W.);<email>liususu@nifdc.org.cn</email>
(S.L.);<email>caoyuan0512@163.com</email>
(Y.C.);<email>chunnan_liang@nifdc.org.cn</email>
(C.L.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lu, Jianjun" sort="Lu, Jianjun" uniqKey="Lu J" first="Jianjun" last="Lu">Jianjun Lu</name>
<affiliation><nlm:aff id="af3-viruses-10-00448">National Center for Safety Evaluation of Drugs, Institute for Food and Drug Safety Evaluation, National Institutes for Food and Drug Control, A8 Hongda Middle Street, Beijing Economic-Technological Development Area, Beijing 100176, China;<email>lujianjun@nifdc.org.cn</email>
(J.L.);<email>yangyanwei@nifdc.org.cn</email>
(Y.Y.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Yang, Yanwei" sort="Yang, Yanwei" uniqKey="Yang Y" first="Yanwei" last="Yang">Yanwei Yang</name>
<affiliation><nlm:aff id="af3-viruses-10-00448">National Center for Safety Evaluation of Drugs, Institute for Food and Drug Safety Evaluation, National Institutes for Food and Drug Control, A8 Hongda Middle Street, Beijing Economic-Technological Development Area, Beijing 100176, China;<email>lujianjun@nifdc.org.cn</email>
(J.L.);<email>yangyanwei@nifdc.org.cn</email>
(Y.Y.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Cao, Yuan" sort="Cao, Yuan" uniqKey="Cao Y" first="Yuan" last="Cao">Yuan Cao</name>
<affiliation><nlm:aff id="af1-viruses-10-00448">Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, Beijing 100050, China;<email>fancf@nifdc.org.cn</email>
(C.F.);<email>wuxi@nifdc.org.cn</email>
(X.W.);<email>liususu@nifdc.org.cn</email>
(S.L.);<email>caoyuan0512@163.com</email>
(Y.C.);<email>chunnan_liang@nifdc.org.cn</email>
(C.L.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Huang, Weijin" sort="Huang, Weijin" uniqKey="Huang W" first="Weijin" last="Huang">Weijin Huang</name>
<affiliation><nlm:aff id="af2-viruses-10-00448">Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, National Institutes for Food and Drug Control, Beijing 100050, China;<email>liuqiang@nifdc.org.cn</email>
(Q.L.);<email>liqianqian1199@163.com</email>
(Q.L.);<email>huangweijin@nifdc.org.cn</email>
(W.H.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Liang, Chunnan" sort="Liang, Chunnan" uniqKey="Liang C" first="Chunnan" last="Liang">Chunnan Liang</name>
<affiliation><nlm:aff id="af1-viruses-10-00448">Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, Beijing 100050, China;<email>fancf@nifdc.org.cn</email>
(C.F.);<email>wuxi@nifdc.org.cn</email>
(X.W.);<email>liususu@nifdc.org.cn</email>
(S.L.);<email>caoyuan0512@163.com</email>
(Y.C.);<email>chunnan_liang@nifdc.org.cn</email>
(C.L.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ying, Tianlei" sort="Ying, Tianlei" uniqKey="Ying T" first="Tianlei" last="Ying">Tianlei Ying</name>
<affiliation><nlm:aff id="af4-viruses-10-00448">Key Laboratory of Medical Molecular Virology of the Ministries of Education and Health, Shanghai Medical College, Fudan University, Shanghai 200032, China;<email>tlying@fudan.edu.cn</email>
(T.Y.);<email>shibojiang@fudan.edu.cn</email>
(S.J.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name>
<affiliation><nlm:aff id="af4-viruses-10-00448">Key Laboratory of Medical Molecular Virology of the Ministries of Education and Health, Shanghai Medical College, Fudan University, Shanghai 200032, China;<email>tlying@fudan.edu.cn</email>
(T.Y.);<email>shibojiang@fudan.edu.cn</email>
(S.J.)</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wang, Youchun" sort="Wang, Youchun" uniqKey="Wang Y" first="Youchun" last="Wang">Youchun Wang</name>
<affiliation><nlm:aff id="af2-viruses-10-00448">Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, National Institutes for Food and Drug Control, Beijing 100050, China;<email>liuqiang@nifdc.org.cn</email>
(Q.L.);<email>liqianqian1199@163.com</email>
(Q.L.);<email>huangweijin@nifdc.org.cn</email>
(W.H.)</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Viruses</title>
<idno type="eISSN">1999-4915</idno>
<imprint><date when="2018">2018</date>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term>
<term>Antibodies, Neutralizing (administration & dosage)</term>
<term>Antibodies, Viral (administration & dosage)</term>
<term>Bacterial Proteins (metabolism)</term>
<term>CRISPR-Associated Protein 9</term>
<term>Clustered Regularly Interspaced Short Palindromic Repeats</term>
<term>Coronavirus Infections (immunology)</term>
<term>Coronavirus Infections (prevention & control)</term>
<term>Coronavirus Infections (virology)</term>
<term>Dipeptidyl Peptidase 4 (genetics)</term>
<term>Dipeptidyl Peptidase 4 (metabolism)</term>
<term>Disease Models, Animal</term>
<term>Disease Susceptibility</term>
<term>Endonucleases (metabolism)</term>
<term>Gene Knock-In Techniques</term>
<term>Humans</term>
<term>Mice</term>
<term>Middle East Respiratory Syndrome Coronavirus (growth & development)</term>
<term>Middle East Respiratory Syndrome Coronavirus (immunology)</term>
<term>Recombination, Genetic</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term>
<term>Anticorps antiviraux (administration et posologie)</term>
<term>Anticorps neutralisants (administration et posologie)</term>
<term>Clustered regularly interspaced short palindromic repeats</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient (croissance et développement)</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie)</term>
<term>Dipeptidyl peptidase 4 (génétique)</term>
<term>Dipeptidyl peptidase 4 (métabolisme)</term>
<term>Endonucleases (métabolisme)</term>
<term>Humains</term>
<term>Infections à coronavirus ()</term>
<term>Infections à coronavirus (immunologie)</term>
<term>Infections à coronavirus (virologie)</term>
<term>Modèles animaux de maladie humaine</term>
<term>Protéines bactériennes (métabolisme)</term>
<term>Recombinaison génétique</term>
<term>Souris</term>
<term>Susceptibilité à une maladie</term>
<term>Techniques de knock-in de gènes</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Antibodies, Neutralizing</term>
<term>Antibodies, Viral</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Dipeptidyl Peptidase 4</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Bacterial Proteins</term>
<term>Dipeptidyl Peptidase 4</term>
<term>Endonucleases</term>
</keywords>
<keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Anticorps antiviraux</term>
<term>Anticorps neutralisants</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>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
<term>Infections à coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Coronavirus Infections</term>
<term>Middle East Respiratory Syndrome Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Dipeptidyl peptidase 4</term>
<term>Endonucleases</term>
<term>Protéines bactériennes</term>
</keywords>
<keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Coronavirus Infections</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>CRISPR-Associated Protein 9</term>
<term>Clustered Regularly Interspaced Short Palindromic Repeats</term>
<term>Disease Models, Animal</term>
<term>Disease Susceptibility</term>
<term>Gene Knock-In Techniques</term>
<term>Humans</term>
<term>Mice</term>
<term>Recombination, Genetic</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Clustered regularly interspaced short palindromic repeats</term>
<term>Humains</term>
<term>Infections à coronavirus</term>
<term>Modèles animaux de maladie humaine</term>
<term>Recombinaison génétique</term>
<term>Souris</term>
<term>Susceptibilité à une maladie</term>
<term>Techniques de knock-in de gènes</term>
</keywords>
</textClass>
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<front><div type="abstract" xml:lang="en"><p>Infection by the Middle East respiratory syndrome coronavirus (MERS-CoV) causes respiratory illness and has a high mortality rate (~35%). The requirement for the virus to be manipulated in a biosafety level three (BSL-3) facility has impeded development of urgently-needed antiviral agents. Here, we established anovel mouse model by inserting human dipeptidyl peptidase 4 (hDPP4) into the Rosa26 locus using CRISPR/Cas9, resulting in global expression of the transgene in a genetically stable mouse line. The mice were highly susceptible to infection by MERS-CoV clinical strain hCoV-EMC, which induced severe diffuse pulmonary disease in the animals, and could also be infected by an optimized pseudotyped MERS-CoV. Administration of the neutralizing monoclonal antibodies, H111-1 and m336, as well as a fusion inhibitor peptide, HR2P-M2, protected mice from challenge with authentic and pseudotyped MERS-CoV. These results confirmed that the hDPP4-knockin mouse is a novel model for studies of MERS-CoV pathogenesis and anti-MERS-CoV antiviral agents in BSL-3 and BSL-2facilities, respectively.</p>
</div>
</front>
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<tree><noCountry><name sortKey="Cao, Yuan" sort="Cao, Yuan" uniqKey="Cao Y" first="Yuan" last="Cao">Yuan Cao</name>
<name sortKey="Fan, Changfa" sort="Fan, Changfa" uniqKey="Fan C" first="Changfa" last="Fan">Changfa Fan</name>
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