Spread of Mutant Middle East Respiratory Syndrome Coronavirus with Reduced Affinity to Human CD26 during the South Korean Outbreak
Identifieur interne : 001017 ( Main/Exploration ); précédent : 001016; suivant : 001018Spread of Mutant Middle East Respiratory Syndrome Coronavirus with Reduced Affinity to Human CD26 during the South Korean Outbreak
Auteurs : Yuri Kim [Corée du Sud] ; Shinhye Cheon [Corée du Sud] ; Chan-Ki Min [Corée du Sud] ; Kyung Mok Sohn [Corée du Sud] ; Ying Jin Kang [Corée du Sud] ; Young-Je Cha [Corée du Sud] ; Ju-Il Kang [Corée du Sud] ; Seong Kyu Han [Corée du Sud] ; Na-Young Ha [Corée du Sud] ; Gwanghun Kim [Corée du Sud] ; Abdimadiyeva Aigerim [Corée du Sud] ; Hyun Mu Shin [Corée du Sud] ; Myung-Sik Choi [Corée du Sud] ; Sanguk Kim [Corée du Sud] ; Hyun-Soo Cho [Corée du Sud] ; Yeon-Sook Kim [Corée du Sud] ; Nam-Hyuk Cho [Corée du Sud]Source :
- mBio [ 2150-7511 ] ; 2016.
Descripteurs français
- KwdFr :
- Adaptation biologique, Analyse de séquence d'ADN, Attachement viral, Coronavirus du syndrome respiratoire du Moyen-Orient (isolement et purification), Coronavirus du syndrome respiratoire du Moyen-Orient (physiologie), Dipeptidyl peptidase 4 (métabolisme), Flambées de maladies, Glycoprotéine de spicule des coronavirus (génétique), Glycoprotéine de spicule des coronavirus (métabolisme), Génome viral, Humains, Infections à coronavirus (virologie), Infections à coronavirus (épidémiologie), Liaison aux protéines, Mutation faux-sens, Mutation ponctuelle, Protéines mutantes (génétique), Protéines mutantes (métabolisme), Récepteurs viraux (métabolisme), République de Corée (épidémiologie), Résonance plasmonique de surface, Sélection génétique.
- MESH :
- génétique : Glycoprotéine de spicule des coronavirus, Protéines mutantes.
- isolement et purification : Coronavirus du syndrome respiratoire du Moyen-Orient.
- métabolisme : Dipeptidyl peptidase 4, Glycoprotéine de spicule des coronavirus, Protéines mutantes, Récepteurs viraux.
- physiologie : Coronavirus du syndrome respiratoire du Moyen-Orient.
- virologie : Infections à coronavirus.
- épidémiologie : Infections à coronavirus, République de Corée.
- Adaptation biologique, Analyse de séquence d'ADN, Attachement viral, Flambées de maladies, Génome viral, Humains, Liaison aux protéines, Mutation faux-sens, Mutation ponctuelle, Résonance plasmonique de surface, Sélection génétique.
English descriptors
- KwdEn :
- Adaptation, Biological, Coronavirus Infections (epidemiology), Coronavirus Infections (virology), Dipeptidyl Peptidase 4 (metabolism), Disease Outbreaks, Genome, Viral, Humans, Middle East Respiratory Syndrome Coronavirus (isolation & purification), Middle East Respiratory Syndrome Coronavirus (physiology), Mutant Proteins (genetics), Mutant Proteins (metabolism), Mutation, Missense, Point Mutation, Protein Binding, Receptors, Virus (metabolism), Republic of Korea (epidemiology), Selection, Genetic, Sequence Analysis, DNA, Spike Glycoprotein, Coronavirus (genetics), Spike Glycoprotein, Coronavirus (metabolism), Surface Plasmon Resonance, Virus Attachment.
- MESH :
- chemical , genetics : Mutant Proteins, Spike Glycoprotein, Coronavirus.
- chemical , metabolism : Dipeptidyl Peptidase 4, Mutant Proteins, Receptors, Virus, Spike Glycoprotein, Coronavirus.
- epidemiology : Coronavirus Infections, Republic of Korea.
- isolation & purification : Middle East Respiratory Syndrome Coronavirus.
- physiology : Middle East Respiratory Syndrome Coronavirus.
- virology : Coronavirus Infections.
- Adaptation, Biological, Disease Outbreaks, Genome, Viral, Humans, Mutation, Missense, Point Mutation, Protein Binding, Selection, Genetic, Sequence Analysis, DNA, Surface Plasmon Resonance, Virus Attachment.
Abstract
The newly emerging Middle East respiratory syndrome coronavirus (MERS-CoV) causes a severe respiratory infection with a high mortality rate (~35%). MERS-CoV has been a global threat due to continuous outbreaks in the Arabian peninsula and international spread by infected travelers since 2012. From May to July 2015, a large outbreak initiated by an infected traveler from the Arabian peninsula swept South Korea and resulted in 186 confirmed cases with 38 deaths (case fatality rate, 20.4%). Here, we show the rapid emergence and spread of a mutant MERS-CoV with reduced affinity to the human CD26 receptor during the South Korean outbreak. We isolated 13 new viral genomes from 14 infected patients treated at a hospital and found that 12 of these genomes possess a point mutation in the receptor-binding domain (RBD) of viral spike (S) protein. Specifically, 11 of these genomes have an I529T mutation in RBD, and 1 has a D510G mutation. Strikingly, both mutations result in reduced affinity of RBD to human CD26 compared to wild-type RBD, as measured by surface plasmon resonance analysis and cellular binding assay. Additionally, pseudotyped virus bearing an I529T mutation in S protein showed reduced entry into host cells compared to virus with wild-type S protein. These unexpected findings suggest that MERS-CoV adaptation during human-to-human spread may be driven by host immunological pressure such as neutralizing antibodies, resulting in reduced affinity to host receptor, and thereby impairs viral fitness and virulence, rather than positive selection for a better affinity to CD26.
Url:
DOI: 10.1128/mBio.00019-16
PubMed: 26933050
PubMed Central: 4810480
Affiliations:
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Le document en format XML
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University of Science and Technology, Pohang</wicri:regionArea><wicri:noRegion>Pohang</wicri:noRegion></affiliation></author><author><name sortKey="Ha, Na Young" sort="Ha, Na Young" uniqKey="Ha N" first="Na-Young" last="Ha">Na-Young Ha</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff2"><addr-line>Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du 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Sud</country><wicri:regionArea>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff2"><addr-line>Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff7"><addr-line>Institute of Endemic Disease, Seoul National University Medical Research Center and Bundang Hospital, Seoul, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Institute of Endemic Disease, Seoul National University Medical Research Center and Bundang Hospital, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Choi, Myung Sik" sort="Choi, Myung Sik" uniqKey="Choi M" first="Myung-Sik" last="Choi">Myung-Sik Choi</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff7"><addr-line>Institute of Endemic Disease, Seoul National University Medical Research Center and Bundang Hospital, Seoul, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Institute of Endemic Disease, Seoul National University Medical Research Center and Bundang Hospital, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Kim, Sanguk" sort="Kim, Sanguk" uniqKey="Kim S" first="Sanguk" last="Kim">Sanguk Kim</name><affiliation wicri:level="1"><nlm:aff id="aff6"><addr-line>Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Life Sciences, Pohang University of Science and Technology, Pohang</wicri:regionArea><wicri:noRegion>Pohang</wicri:noRegion></affiliation></author><author><name sortKey="Cho, Hyun Soo" sort="Cho, Hyun Soo" uniqKey="Cho H" first="Hyun-Soo" last="Cho">Hyun-Soo Cho</name><affiliation wicri:level="3"><nlm:aff id="aff4"><addr-line>Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Kim, Yeon Sook" sort="Kim, Yeon Sook" uniqKey="Kim Y" first="Yeon-Sook" last="Kim">Yeon-Sook Kim</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Division of Infectious Diseases, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Division of Infectious Diseases, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon</wicri:regionArea><wicri:noRegion>Daejeon</wicri:noRegion></affiliation></author><author><name sortKey="Cho, Nam Hyuk" sort="Cho, Nam Hyuk" uniqKey="Cho N" first="Nam-Hyuk" last="Cho">Nam-Hyuk Cho</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff2"><addr-line>Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff7"><addr-line>Institute of Endemic Disease, Seoul National University Medical Research Center and Bundang Hospital, Seoul, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Institute of Endemic Disease, Seoul National University Medical Research Center and Bundang Hospital, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de 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id="aff1"><addr-line>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff2"><addr-line>Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Cheon, Shinhye" sort="Cheon, Shinhye" uniqKey="Cheon S" first="Shinhye" last="Cheon">Shinhye Cheon</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Division of Infectious Diseases, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Division of Infectious Diseases, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon</wicri:regionArea><wicri:noRegion>Daejeon</wicri:noRegion></affiliation></author><author><name sortKey="Min, Chan Ki" sort="Min, Chan Ki" uniqKey="Min C" first="Chan-Ki" last="Min">Chan-Ki Min</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff2"><addr-line>Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Sohn, Kyung Mok" sort="Sohn, Kyung Mok" uniqKey="Sohn K" first="Kyung Mok" last="Sohn">Kyung Mok Sohn</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Division of Infectious Diseases, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Division of Infectious Diseases, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon</wicri:regionArea><wicri:noRegion>Daejeon</wicri:noRegion></affiliation></author><author><name sortKey="Kang, Ying Jin" sort="Kang, Ying Jin" uniqKey="Kang Y" first="Ying Jin" last="Kang">Ying Jin Kang</name><affiliation wicri:level="3"><nlm:aff id="aff4"><addr-line>Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Cha, Young Je" sort="Cha, Young Je" uniqKey="Cha Y" first="Young-Je" last="Cha">Young-Je Cha</name><affiliation wicri:level="3"><nlm:aff id="aff4"><addr-line>Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Kang, Ju Il" sort="Kang, Ju Il" uniqKey="Kang J" first="Ju-Il" last="Kang">Ju-Il Kang</name><affiliation wicri:level="3"><nlm:aff id="aff5"><addr-line>Institute of Biotechnology, Cosmogenetech Inc., Seoul, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Institute of Biotechnology, Cosmogenetech Inc., Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Han, Seong Kyu" sort="Han, Seong Kyu" uniqKey="Han S" first="Seong Kyu" last="Han">Seong Kyu Han</name><affiliation wicri:level="1"><nlm:aff id="aff6"><addr-line>Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Life Sciences, Pohang University of Science and Technology, Pohang</wicri:regionArea><wicri:noRegion>Pohang</wicri:noRegion></affiliation></author><author><name sortKey="Ha, Na Young" sort="Ha, Na Young" uniqKey="Ha N" first="Na-Young" last="Ha">Na-Young Ha</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff2"><addr-line>Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Kim, Gwanghun" sort="Kim, Gwanghun" uniqKey="Kim G" first="Gwanghun" last="Kim">Gwanghun Kim</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff2"><addr-line>Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Aigerim, Abdimadiyeva" sort="Aigerim, Abdimadiyeva" uniqKey="Aigerim A" first="Abdimadiyeva" last="Aigerim">Abdimadiyeva Aigerim</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff2"><addr-line>Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Shin, Hyun Mu" sort="Shin, Hyun Mu" uniqKey="Shin H" first="Hyun Mu" last="Shin">Hyun Mu Shin</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff2"><addr-line>Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff7"><addr-line>Institute of Endemic Disease, Seoul National University Medical Research Center and Bundang Hospital, Seoul, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Institute of Endemic Disease, Seoul National University Medical Research Center and Bundang Hospital, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Choi, Myung Sik" sort="Choi, Myung Sik" uniqKey="Choi M" first="Myung-Sik" last="Choi">Myung-Sik Choi</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff7"><addr-line>Institute of Endemic Disease, Seoul National University Medical Research Center and Bundang Hospital, Seoul, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Institute of Endemic Disease, Seoul National University Medical Research Center and Bundang Hospital, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Kim, Sanguk" sort="Kim, Sanguk" uniqKey="Kim S" first="Sanguk" last="Kim">Sanguk Kim</name><affiliation wicri:level="1"><nlm:aff id="aff6"><addr-line>Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Life Sciences, Pohang University of Science and Technology, Pohang</wicri:regionArea><wicri:noRegion>Pohang</wicri:noRegion></affiliation></author><author><name sortKey="Cho, Hyun Soo" sort="Cho, Hyun Soo" uniqKey="Cho H" first="Hyun-Soo" last="Cho">Hyun-Soo Cho</name><affiliation wicri:level="3"><nlm:aff id="aff4"><addr-line>Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Kim, Yeon Sook" sort="Kim, Yeon Sook" uniqKey="Kim Y" first="Yeon-Sook" last="Kim">Yeon-Sook Kim</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Division of Infectious Diseases, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Division of Infectious Diseases, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon</wicri:regionArea><wicri:noRegion>Daejeon</wicri:noRegion></affiliation></author><author><name sortKey="Cho, Nam Hyuk" sort="Cho, Nam Hyuk" uniqKey="Cho N" first="Nam-Hyuk" last="Cho">Nam-Hyuk Cho</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff2"><addr-line>Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff7"><addr-line>Institute of Endemic Disease, Seoul National University Medical Research Center and Bundang Hospital, Seoul, Republic of Korea</addr-line></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Institute of Endemic Disease, Seoul National University Medical Research Center and Bundang Hospital, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author></analytic><series><title level="j">mBio</title><idno type="eISSN">2150-7511</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adaptation, Biological</term><term>Coronavirus Infections (epidemiology)</term><term>Coronavirus Infections (virology)</term><term>Dipeptidyl Peptidase 4 (metabolism)</term><term>Disease Outbreaks</term><term>Genome, Viral</term><term>Humans</term><term>Middle East Respiratory Syndrome Coronavirus (isolation & purification)</term><term>Middle East Respiratory Syndrome Coronavirus (physiology)</term><term>Mutant Proteins (genetics)</term><term>Mutant Proteins (metabolism)</term><term>Mutation, Missense</term><term>Point Mutation</term><term>Protein Binding</term><term>Receptors, Virus (metabolism)</term><term>Republic of Korea (epidemiology)</term><term>Selection, Genetic</term><term>Sequence Analysis, DNA</term><term>Spike Glycoprotein, Coronavirus (genetics)</term><term>Spike Glycoprotein, Coronavirus (metabolism)</term><term>Surface Plasmon Resonance</term><term>Virus Attachment</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adaptation biologique</term><term>Analyse de séquence d'ADN</term><term>Attachement viral</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (isolement et purification)</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (physiologie)</term><term>Dipeptidyl peptidase 4 (métabolisme)</term><term>Flambées de maladies</term><term>Glycoprotéine de spicule des coronavirus (génétique)</term><term>Glycoprotéine de spicule des coronavirus (métabolisme)</term><term>Génome viral</term><term>Humains</term><term>Infections à coronavirus (virologie)</term><term>Infections à coronavirus (épidémiologie)</term><term>Liaison aux protéines</term><term>Mutation faux-sens</term><term>Mutation ponctuelle</term><term>Protéines mutantes (génétique)</term><term>Protéines mutantes (métabolisme)</term><term>Récepteurs viraux (métabolisme)</term><term>République de Corée (épidémiologie)</term><term>Résonance plasmonique de surface</term><term>Sélection génétique</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Mutant Proteins</term><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Dipeptidyl Peptidase 4</term><term>Mutant Proteins</term><term>Receptors, Virus</term><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" qualifier="epidemiology" xml:lang="en"><term>Coronavirus Infections</term><term>Republic of Korea</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Glycoprotéine de spicule des coronavirus</term><term>Protéines mutantes</term></keywords><keywords scheme="MESH" qualifier="isolation & purification" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="isolement et purification" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Dipeptidyl peptidase 4</term><term>Glycoprotéine de spicule des coronavirus</term><term>Protéines mutantes</term><term>Récepteurs viraux</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</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="épidémiologie" xml:lang="fr"><term>Infections à coronavirus</term><term>République de Corée</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adaptation, Biological</term><term>Disease Outbreaks</term><term>Genome, Viral</term><term>Humans</term><term>Mutation, Missense</term><term>Point Mutation</term><term>Protein Binding</term><term>Selection, Genetic</term><term>Sequence Analysis, DNA</term><term>Surface Plasmon Resonance</term><term>Virus Attachment</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adaptation biologique</term><term>Analyse de séquence d'ADN</term><term>Attachement viral</term><term>Flambées de maladies</term><term>Génome viral</term><term>Humains</term><term>Liaison aux protéines</term><term>Mutation faux-sens</term><term>Mutation ponctuelle</term><term>Résonance plasmonique de surface</term><term>Sélection génétique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>ABSTRACT</title><p>The newly emerging Middle East respiratory syndrome coronavirus (MERS-CoV) causes a severe respiratory infection with a high mortality rate (~35%). MERS-CoV has been a global threat due to continuous outbreaks in the Arabian peninsula and international spread by infected travelers since 2012. From May to July 2015, a large outbreak initiated by an infected traveler from the Arabian peninsula swept South Korea and resulted in 186 confirmed cases with 38 deaths (case fatality rate, 20.4%). Here, we show the rapid emergence and spread of a mutant MERS-CoV with reduced affinity to the human CD26 receptor during the South Korean outbreak. We isolated 13 new viral genomes from 14 infected patients treated at a hospital and found that 12 of these genomes possess a point mutation in the receptor-binding domain (RBD) of viral spike (S) protein. Specifically, 11 of these genomes have an I529T mutation in RBD, and 1 has a D510G mutation. Strikingly, both mutations result in reduced affinity of RBD to human CD26 compared to wild-type RBD, as measured by surface plasmon resonance analysis and cellular binding assay. Additionally, pseudotyped virus bearing an I529T mutation in S protein showed reduced entry into host cells compared to virus with wild-type S protein. These unexpected findings suggest that MERS-CoV adaptation during human-to-human spread may be driven by host immunological pressure such as neutralizing antibodies, resulting in reduced affinity to host receptor, and thereby impairs viral fitness and virulence, rather than positive selection for a better affinity to CD26.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Chan, Jf" uniqKey="Chan J">JF Chan</name></author><author><name sortKey="Lau, Sk" uniqKey="Lau S">SK Lau</name></author><author><name sortKey="To, Kk" uniqKey="To K">KK To</name></author><author><name sortKey="Cheng, Vc" uniqKey="Cheng V">VC Cheng</name></author><author><name sortKey="Woo, Pc" uniqKey="Woo P">PC Woo</name></author><author><name sortKey="Yuen, Ky" uniqKey="Yuen K">KY Yuen</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Oboho, Ik" uniqKey="Oboho I">IK Oboho</name></author><author><name 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sortKey="Wallace, Jc" uniqKey="Wallace J">JC Wallace</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, N" uniqKey="Wang N">N Wang</name></author><author><name sortKey="Shi, X" uniqKey="Shi X">X Shi</name></author><author><name sortKey="Jiang, L" uniqKey="Jiang L">L Jiang</name></author><author><name sortKey="Zhang, S" uniqKey="Zhang S">S Zhang</name></author><author><name sortKey="Wang, D" uniqKey="Wang D">D Wang</name></author><author><name sortKey="Tong, P" uniqKey="Tong P">P Tong</name></author><author><name sortKey="Guo, D" uniqKey="Guo D">D Guo</name></author><author><name sortKey="Fu, L" uniqKey="Fu L">L Fu</name></author><author><name sortKey="Cui, Y" uniqKey="Cui Y">Y Cui</name></author><author><name sortKey="Liu, X" uniqKey="Liu X">X Liu</name></author><author><name sortKey="Arledge, Kc" uniqKey="Arledge K">KC Arledge</name></author><author><name sortKey="Chen, Yh" uniqKey="Chen Y">YH Chen</name></author><author><name sortKey="Zhang, L" uniqKey="Zhang L">L Zhang</name></author><author><name sortKey="Wang, X" uniqKey="Wang X">X Wang</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Corée du Sud</li></country><region><li>Région capitale de Séoul</li></region><settlement><li>Séoul</li></settlement></list><tree><country name="Corée du Sud"><region name="Région capitale de Séoul"><name sortKey="Kim, Yuri" sort="Kim, Yuri" uniqKey="Kim Y" first="Yuri" last="Kim">Yuri Kim</name></region><name sortKey="Aigerim, Abdimadiyeva" sort="Aigerim, Abdimadiyeva" uniqKey="Aigerim A" first="Abdimadiyeva" last="Aigerim">Abdimadiyeva Aigerim</name><name sortKey="Aigerim, Abdimadiyeva" sort="Aigerim, Abdimadiyeva" uniqKey="Aigerim A" first="Abdimadiyeva" last="Aigerim">Abdimadiyeva Aigerim</name><name sortKey="Cha, Young Je" sort="Cha, Young Je" uniqKey="Cha Y" first="Young-Je" last="Cha">Young-Je Cha</name><name sortKey="Cheon, Shinhye" sort="Cheon, Shinhye" uniqKey="Cheon S" first="Shinhye" last="Cheon">Shinhye Cheon</name><name sortKey="Cho, Hyun Soo" sort="Cho, Hyun Soo" uniqKey="Cho H" first="Hyun-Soo" last="Cho">Hyun-Soo Cho</name><name sortKey="Cho, Nam Hyuk" sort="Cho, Nam Hyuk" uniqKey="Cho N" first="Nam-Hyuk" last="Cho">Nam-Hyuk Cho</name><name sortKey="Cho, Nam Hyuk" sort="Cho, Nam Hyuk" uniqKey="Cho N" first="Nam-Hyuk" last="Cho">Nam-Hyuk Cho</name><name sortKey="Cho, Nam Hyuk" sort="Cho, Nam Hyuk" uniqKey="Cho N" first="Nam-Hyuk" last="Cho">Nam-Hyuk Cho</name><name sortKey="Choi, Myung Sik" sort="Choi, Myung Sik" uniqKey="Choi M" first="Myung-Sik" last="Choi">Myung-Sik Choi</name><name sortKey="Choi, Myung Sik" sort="Choi, Myung Sik" uniqKey="Choi M" first="Myung-Sik" last="Choi">Myung-Sik Choi</name><name sortKey="Ha, Na Young" sort="Ha, Na Young" uniqKey="Ha N" first="Na-Young" last="Ha">Na-Young Ha</name><name sortKey="Ha, Na Young" sort="Ha, Na Young" uniqKey="Ha N" first="Na-Young" last="Ha">Na-Young Ha</name><name sortKey="Han, Seong Kyu" sort="Han, Seong Kyu" uniqKey="Han S" first="Seong Kyu" last="Han">Seong Kyu Han</name><name sortKey="Kang, Ju Il" sort="Kang, Ju Il" uniqKey="Kang J" first="Ju-Il" last="Kang">Ju-Il Kang</name><name sortKey="Kang, Ying Jin" sort="Kang, Ying Jin" uniqKey="Kang Y" first="Ying Jin" last="Kang">Ying Jin Kang</name><name sortKey="Kim, Gwanghun" sort="Kim, Gwanghun" uniqKey="Kim G" first="Gwanghun" last="Kim">Gwanghun Kim</name><name sortKey="Kim, Gwanghun" sort="Kim, Gwanghun" uniqKey="Kim G" first="Gwanghun" last="Kim">Gwanghun Kim</name><name sortKey="Kim, Sanguk" sort="Kim, Sanguk" uniqKey="Kim S" first="Sanguk" last="Kim">Sanguk Kim</name><name sortKey="Kim, Yeon Sook" sort="Kim, Yeon Sook" uniqKey="Kim Y" first="Yeon-Sook" last="Kim">Yeon-Sook Kim</name><name sortKey="Kim, Yuri" sort="Kim, Yuri" uniqKey="Kim Y" first="Yuri" last="Kim">Yuri Kim</name><name sortKey="Min, Chan Ki" sort="Min, Chan Ki" uniqKey="Min C" first="Chan-Ki" last="Min">Chan-Ki Min</name><name sortKey="Min, Chan Ki" sort="Min, Chan Ki" uniqKey="Min C" first="Chan-Ki" last="Min">Chan-Ki Min</name><name sortKey="Shin, Hyun Mu" sort="Shin, Hyun Mu" uniqKey="Shin H" first="Hyun Mu" last="Shin">Hyun Mu Shin</name><name sortKey="Shin, Hyun Mu" sort="Shin, Hyun Mu" uniqKey="Shin H" first="Hyun Mu" last="Shin">Hyun Mu Shin</name><name sortKey="Shin, Hyun Mu" sort="Shin, Hyun Mu" uniqKey="Shin H" first="Hyun Mu" last="Shin">Hyun Mu Shin</name><name sortKey="Sohn, Kyung Mok" sort="Sohn, Kyung Mok" uniqKey="Sohn K" first="Kyung Mok" last="Sohn">Kyung Mok Sohn</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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