MERS coronavirus induces apoptosis in kidney and lung by upregulating Smad7 and FGF2.
Identifieur interne : 001026 ( PubMed/Checkpoint ); précédent : 001025; suivant : 001027MERS coronavirus induces apoptosis in kidney and lung by upregulating Smad7 and FGF2.
Auteurs : Man-Lung Yeung [République populaire de Chine] ; Yanfeng Yao [République populaire de Chine] ; Lilong Jia [République populaire de Chine] ; Jasper F W. Chan [République populaire de Chine] ; Kwok-Hung Chan [République populaire de Chine] ; Kwok-Fan Cheung [République populaire de Chine] ; Honglin Chen [République populaire de Chine] ; Vincent K M. Poon [République populaire de Chine] ; Alan K L. Tsang [République populaire de Chine] ; Kelvin K W. To [République populaire de Chine] ; Ming-Kwong Yiu [République populaire de Chine] ; Jade L L. Teng [République populaire de Chine] ; Hin Chu [République populaire de Chine] ; Jie Zhou [République populaire de Chine] ; Qing Zhang [République populaire de Chine] ; Wei Deng [République populaire de Chine] ; Susanna K P. Lau [République populaire de Chine] ; Johnson Y N. Lau [République populaire de Chine] ; Patrick C Y. Woo [République populaire de Chine] ; Tak-Mao Chan [République populaire de Chine] ; Susan Yung [République populaire de Chine] ; Bo-Jian Zheng [République populaire de Chine] ; Dong-Yan Jin [République populaire de Chine] ; Peter W. Mathieson [République populaire de Chine] ; Chuan Qin [République populaire de Chine] ; Kwok-Yung Yuen [République populaire de Chine]Source :
- Nature microbiology [ 2058-5276 ] ; 2016.
Descripteurs français
- KwdFr :
- Animaux, Apoptose, Callithrix, Coronavirus du syndrome respiratoire du Moyen-Orient (pathogénicité), Effet cytopathogène viral, Facteur de croissance fibroblastique de type 2 (métabolisme), Humains, Infections à coronavirus (anatomopathologie), Interactions hôte-pathogène, Modèles animaux de maladie humaine, Poumon (anatomopathologie), Protéine Smad7 (métabolisme), Rein (anatomopathologie), Techniques de culture d'organes.
- MESH :
- anatomopathologie : Infections à coronavirus, Poumon, Rein.
- métabolisme : Facteur de croissance fibroblastique de type 2, Protéine Smad7.
- pathogénicité : Coronavirus du syndrome respiratoire du Moyen-Orient.
- Animaux, Apoptose, Callithrix, Effet cytopathogène viral, Humains, Interactions hôte-pathogène, Modèles animaux de maladie humaine, Techniques de culture d'organes.
English descriptors
- KwdEn :
- Animals, Apoptosis, Callithrix, Coronavirus Infections (pathology), Cytopathogenic Effect, Viral, Disease Models, Animal, Fibroblast Growth Factor 2 (metabolism), Host-Pathogen Interactions, Humans, Kidney (pathology), Lung (pathology), Middle East Respiratory Syndrome Coronavirus (pathogenicity), Organ Culture Techniques, Smad7 Protein (metabolism).
- MESH :
- chemical , metabolism : Fibroblast Growth Factor 2, Smad7 Protein.
- pathogenicity : Middle East Respiratory Syndrome Coronavirus.
- pathology : Coronavirus Infections, Kidney, Lung.
- Animals, Apoptosis, Callithrix, Cytopathogenic Effect, Viral, Disease Models, Animal, Host-Pathogen Interactions, Humans, Organ Culture Techniques.
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) causes sporadic zoonotic disease and healthcare-associated outbreaks in human. MERS is often complicated by acute respiratory distress syndrome (ARDS) and multi-organ failure(1,2). The high incidence of renal failure in MERS is a unique clinical feature not often found in other human coronavirus infections(3,4). Whether MERS-CoV infects the kidney and how it triggers renal failure are not understood(5,6). Here, we demonstrated renal infection and apoptotic induction by MERS-CoV in human ex vivo organ culture and a nonhuman primate model. High-throughput analysis revealed that the cellular genes most significantly perturbed by MERS-CoV have previously been implicated in renal diseases. Furthermore, MERS-CoV induced apoptosis through upregulation of Smad7 and fibroblast growth factor 2 (FGF2) expression in both kidney and lung cells. Conversely, knockdown of Smad7 effectively inhibited MERS-CoV replication and protected cells from virus-induced cytopathic effects. We further demonstrated that hyperexpression of Smad7 or FGF2 induced a strong apoptotic response in kidney cells. Common marmosets infected by MERS-CoV developed ARDS and disseminated infection in kidneys and other organs. Smad7 and FGF2 expression were elevated in the lungs and kidneys of the infected animals. Our results provide insights into the pathogenesis of MERS-CoV and host targets for treatment.
DOI: 10.1038/nmicrobiol.2016.4
PubMed: 27572168
Affiliations:
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Poon</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Tsang, Alan K L" sort="Tsang, Alan K L" uniqKey="Tsang A" first="Alan K L" last="Tsang">Alan K L. Tsang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="To, Kelvin K W" sort="To, Kelvin K W" uniqKey="To K" first="Kelvin K W" last="To">Kelvin K W. 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Teng</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Chu, Hin" sort="Chu, Hin" uniqKey="Chu H" first="Hin" last="Chu">Hin Chu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Zhou, Jie" sort="Zhou, Jie" uniqKey="Zhou J" first="Jie" last="Zhou">Jie Zhou</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Qing" sort="Zhang, Qing" uniqKey="Zhang Q" first="Qing" last="Zhang">Qing Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Deng, Wei" sort="Deng, Wei" uniqKey="Deng W" first="Wei" last="Deng">Wei Deng</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences, Chaoyang District, Beijing, 100021, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences, Chaoyang District, Beijing, 100021</wicri:regionArea><wicri:noRegion>100021</wicri:noRegion></affiliation></author><author><name sortKey="Lau, Susanna K P" sort="Lau, Susanna K P" uniqKey="Lau S" first="Susanna K P" last="Lau">Susanna K P. Lau</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Lau, Johnson Y N" sort="Lau, Johnson Y N" uniqKey="Lau J" first="Johnson Y N" last="Lau">Johnson Y N. Lau</name><affiliation wicri:level="1"><nlm:affiliation>Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Woo, Patrick C Y" sort="Woo, Patrick C Y" uniqKey="Woo P" first="Patrick C Y" last="Woo">Patrick C Y. Woo</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Chan, Tak Mao" sort="Chan, Tak Mao" uniqKey="Chan T" first="Tak-Mao" last="Chan">Tak-Mao Chan</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Yung, Susan" sort="Yung, Susan" uniqKey="Yung S" first="Susan" last="Yung">Susan Yung</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Zheng, Bo Jian" sort="Zheng, Bo Jian" uniqKey="Zheng B" first="Bo-Jian" last="Zheng">Bo-Jian Zheng</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Jin, Dong Yan" sort="Jin, Dong Yan" uniqKey="Jin D" first="Dong-Yan" last="Jin">Dong-Yan Jin</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Biochemistry, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Mathieson, Peter W" sort="Mathieson, Peter W" uniqKey="Mathieson P" first="Peter W" last="Mathieson">Peter W. Mathieson</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Qin, Chuan" sort="Qin, Chuan" uniqKey="Qin C" first="Chuan" last="Qin">Chuan Qin</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences, Chaoyang District, Beijing, 100021, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences, Chaoyang District, Beijing, 100021</wicri:regionArea><wicri:noRegion>100021</wicri:noRegion></affiliation></author><author><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:27572168</idno><idno type="pmid">27572168</idno><idno type="doi">10.1038/nmicrobiol.2016.4</idno><idno type="wicri:Area/PubMed/Corpus">000F90</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000F90</idno><idno type="wicri:Area/PubMed/Curation">000F90</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000F90</idno><idno type="wicri:Area/PubMed/Checkpoint">001026</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001026</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">MERS coronavirus induces apoptosis in kidney and lung by upregulating Smad7 and FGF2.</title><author><name sortKey="Yeung, Man Lung" sort="Yeung, Man Lung" uniqKey="Yeung M" first="Man-Lung" last="Yeung">Man-Lung Yeung</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Yao, Yanfeng" sort="Yao, Yanfeng" uniqKey="Yao Y" first="Yanfeng" last="Yao">Yanfeng Yao</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences, Chaoyang District, Beijing, 100021, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences, Chaoyang District, Beijing, 100021</wicri:regionArea><wicri:noRegion>100021</wicri:noRegion></affiliation></author><author><name sortKey="Jia, Lilong" sort="Jia, Lilong" uniqKey="Jia L" first="Lilong" last="Jia">Lilong Jia</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Chan, Jasper F W" sort="Chan, Jasper F W" uniqKey="Chan J" first="Jasper F W" last="Chan">Jasper F W. Chan</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Chan, Kwok Hung" sort="Chan, Kwok Hung" uniqKey="Chan K" first="Kwok-Hung" last="Chan">Kwok-Hung Chan</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Cheung, Kwok Fan" sort="Cheung, Kwok Fan" uniqKey="Cheung K" first="Kwok-Fan" last="Cheung">Kwok-Fan Cheung</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Honglin" sort="Chen, Honglin" uniqKey="Chen H" first="Honglin" last="Chen">Honglin Chen</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Poon, Vincent K M" sort="Poon, Vincent K M" uniqKey="Poon V" first="Vincent K M" last="Poon">Vincent K M. Poon</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Tsang, Alan K L" sort="Tsang, Alan K L" uniqKey="Tsang A" first="Alan K L" last="Tsang">Alan K L. Tsang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="To, Kelvin K W" sort="To, Kelvin K W" uniqKey="To K" first="Kelvin K W" last="To">Kelvin K W. To</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Yiu, Ming Kwong" sort="Yiu, Ming Kwong" uniqKey="Yiu M" first="Ming-Kwong" last="Yiu">Ming-Kwong Yiu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Surgery, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Surgery, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Teng, Jade L L" sort="Teng, Jade L L" uniqKey="Teng J" first="Jade L L" last="Teng">Jade L L. Teng</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Chu, Hin" sort="Chu, Hin" uniqKey="Chu H" first="Hin" last="Chu">Hin Chu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Zhou, Jie" sort="Zhou, Jie" uniqKey="Zhou J" first="Jie" last="Zhou">Jie Zhou</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Qing" sort="Zhang, Qing" uniqKey="Zhang Q" first="Qing" last="Zhang">Qing Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Deng, Wei" sort="Deng, Wei" uniqKey="Deng W" first="Wei" last="Deng">Wei Deng</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences, Chaoyang District, Beijing, 100021, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences, Chaoyang District, Beijing, 100021</wicri:regionArea><wicri:noRegion>100021</wicri:noRegion></affiliation></author><author><name sortKey="Lau, Susanna K P" sort="Lau, Susanna K P" uniqKey="Lau S" first="Susanna K P" last="Lau">Susanna K P. Lau</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Lau, Johnson Y N" sort="Lau, Johnson Y N" uniqKey="Lau J" first="Johnson Y N" last="Lau">Johnson Y N. Lau</name><affiliation wicri:level="1"><nlm:affiliation>Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Woo, Patrick C Y" sort="Woo, Patrick C Y" uniqKey="Woo P" first="Patrick C Y" last="Woo">Patrick C Y. Woo</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Chan, Tak Mao" sort="Chan, Tak Mao" uniqKey="Chan T" first="Tak-Mao" last="Chan">Tak-Mao Chan</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Yung, Susan" sort="Yung, Susan" uniqKey="Yung S" first="Susan" last="Yung">Susan Yung</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Zheng, Bo Jian" sort="Zheng, Bo Jian" uniqKey="Zheng B" first="Bo-Jian" last="Zheng">Bo-Jian Zheng</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Jin, Dong Yan" sort="Jin, Dong Yan" uniqKey="Jin D" first="Dong-Yan" last="Jin">Dong-Yan Jin</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Biochemistry, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Mathieson, Peter W" sort="Mathieson, Peter W" uniqKey="Mathieson P" first="Peter W" last="Mathieson">Peter W. Mathieson</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Qin, Chuan" sort="Qin, Chuan" uniqKey="Qin C" first="Chuan" last="Qin">Chuan Qin</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences, Chaoyang District, Beijing, 100021, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences, Chaoyang District, Beijing, 100021</wicri:regionArea><wicri:noRegion>100021</wicri:noRegion></affiliation></author><author><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author></analytic><series><title level="j">Nature microbiology</title><idno type="eISSN">2058-5276</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Apoptosis</term><term>Callithrix</term><term>Coronavirus Infections (pathology)</term><term>Cytopathogenic Effect, Viral</term><term>Disease Models, Animal</term><term>Fibroblast Growth Factor 2 (metabolism)</term><term>Host-Pathogen Interactions</term><term>Humans</term><term>Kidney (pathology)</term><term>Lung (pathology)</term><term>Middle East Respiratory Syndrome Coronavirus (pathogenicity)</term><term>Organ Culture Techniques</term><term>Smad7 Protein (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Apoptose</term><term>Callithrix</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (pathogénicité)</term><term>Effet cytopathogène viral</term><term>Facteur de croissance fibroblastique de type 2 (métabolisme)</term><term>Humains</term><term>Infections à coronavirus (anatomopathologie)</term><term>Interactions hôte-pathogène</term><term>Modèles animaux de maladie humaine</term><term>Poumon (anatomopathologie)</term><term>Protéine Smad7 (métabolisme)</term><term>Rein (anatomopathologie)</term><term>Techniques de culture d'organes</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Fibroblast Growth Factor 2</term><term>Smad7 Protein</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Infections à coronavirus</term><term>Poumon</term><term>Rein</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Facteur de croissance fibroblastique de type 2</term><term>Protéine Smad7</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="pathology" xml:lang="en"><term>Coronavirus Infections</term><term>Kidney</term><term>Lung</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Apoptosis</term><term>Callithrix</term><term>Cytopathogenic Effect, Viral</term><term>Disease Models, Animal</term><term>Host-Pathogen Interactions</term><term>Humans</term><term>Organ Culture Techniques</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Apoptose</term><term>Callithrix</term><term>Effet cytopathogène viral</term><term>Humains</term><term>Interactions hôte-pathogène</term><term>Modèles animaux de maladie humaine</term><term>Techniques de culture d'organes</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Middle East respiratory syndrome coronavirus (MERS-CoV) causes sporadic zoonotic disease and healthcare-associated outbreaks in human. MERS is often complicated by acute respiratory distress syndrome (ARDS) and multi-organ failure(1,2). The high incidence of renal failure in MERS is a unique clinical feature not often found in other human coronavirus infections(3,4). Whether MERS-CoV infects the kidney and how it triggers renal failure are not understood(5,6). Here, we demonstrated renal infection and apoptotic induction by MERS-CoV in human ex vivo organ culture and a nonhuman primate model. High-throughput analysis revealed that the cellular genes most significantly perturbed by MERS-CoV have previously been implicated in renal diseases. Furthermore, MERS-CoV induced apoptosis through upregulation of Smad7 and fibroblast growth factor 2 (FGF2) expression in both kidney and lung cells. Conversely, knockdown of Smad7 effectively inhibited MERS-CoV replication and protected cells from virus-induced cytopathic effects. We further demonstrated that hyperexpression of Smad7 or FGF2 induced a strong apoptotic response in kidney cells. Common marmosets infected by MERS-CoV developed ARDS and disseminated infection in kidneys and other organs. Smad7 and FGF2 expression were elevated in the lungs and kidneys of the infected animals. Our results provide insights into the pathogenesis of MERS-CoV and host targets for treatment. </div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">27572168</PMID><DateCompleted><Year>2018</Year><Month>01</Month><Day>29</Day></DateCompleted><DateRevised><Year>2020</Year><Month>03</Month><Day>27</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">2058-5276</ISSN><JournalIssue CitedMedium="Internet"><Volume>1</Volume><PubDate><Year>2016</Year><Month>Feb</Month><Day>22</Day></PubDate></JournalIssue><Title>Nature microbiology</Title><ISOAbbreviation>Nat Microbiol</ISOAbbreviation></Journal><ArticleTitle>MERS coronavirus induces apoptosis in kidney and lung by upregulating Smad7 and FGF2.</ArticleTitle><Pagination><MedlinePgn>16004</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/nmicrobiol.2016.4</ELocationID><Abstract><AbstractText>Middle East respiratory syndrome coronavirus (MERS-CoV) causes sporadic zoonotic disease and healthcare-associated outbreaks in human. MERS is often complicated by acute respiratory distress syndrome (ARDS) and multi-organ failure(1,2). The high incidence of renal failure in MERS is a unique clinical feature not often found in other human coronavirus infections(3,4). Whether MERS-CoV infects the kidney and how it triggers renal failure are not understood(5,6). Here, we demonstrated renal infection and apoptotic induction by MERS-CoV in human ex vivo organ culture and a nonhuman primate model. High-throughput analysis revealed that the cellular genes most significantly perturbed by MERS-CoV have previously been implicated in renal diseases. Furthermore, MERS-CoV induced apoptosis through upregulation of Smad7 and fibroblast growth factor 2 (FGF2) expression in both kidney and lung cells. Conversely, knockdown of Smad7 effectively inhibited MERS-CoV replication and protected cells from virus-induced cytopathic effects. We further demonstrated that hyperexpression of Smad7 or FGF2 induced a strong apoptotic response in kidney cells. Common marmosets infected by MERS-CoV developed ARDS and disseminated infection in kidneys and other organs. Smad7 and FGF2 expression were elevated in the lungs and kidneys of the infected animals. Our results provide insights into the pathogenesis of MERS-CoV and host targets for treatment. </AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Yeung</LastName><ForeName>Man-Lung</ForeName><Initials>ML</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yao</LastName><ForeName>Yanfeng</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences, Chaoyang District, Beijing, 100021, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jia</LastName><ForeName>Lilong</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chan</LastName><ForeName>Jasper F W</ForeName><Initials>JF</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chan</LastName><ForeName>Kwok-Hung</ForeName><Initials>KH</Initials><AffiliationInfo><Affiliation>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cheung</LastName><ForeName>Kwok-Fan</ForeName><Initials>KF</Initials><AffiliationInfo><Affiliation>Department of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Honglin</ForeName><Initials>H</Initials><Identifier Source="ORCID">http://orcid.org/0000-0001-5108-8338</Identifier><AffiliationInfo><Affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Poon</LastName><ForeName>Vincent K M</ForeName><Initials>VK</Initials><AffiliationInfo><Affiliation>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tsang</LastName><ForeName>Alan K L</ForeName><Initials>AK</Initials><AffiliationInfo><Affiliation>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>To</LastName><ForeName>Kelvin K W</ForeName><Initials>KK</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yiu</LastName><ForeName>Ming-Kwong</ForeName><Initials>MK</Initials><AffiliationInfo><Affiliation>Department of Surgery, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Teng</LastName><ForeName>Jade L L</ForeName><Initials>JL</Initials><AffiliationInfo><Affiliation>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chu</LastName><ForeName>Hin</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhou</LastName><ForeName>Jie</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Qing</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>Department of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Deng</LastName><ForeName>Wei</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences, Chaoyang District, Beijing, 100021, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lau</LastName><ForeName>Susanna K P</ForeName><Initials>SK</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lau</LastName><ForeName>Johnson Y N</ForeName><Initials>JY</Initials><AffiliationInfo><Affiliation>Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Woo</LastName><ForeName>Patrick C Y</ForeName><Initials>PC</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chan</LastName><ForeName>Tak-Mao</ForeName><Initials>TM</Initials><AffiliationInfo><Affiliation>Department of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yung</LastName><ForeName>Susan</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zheng</LastName><ForeName>Bo-Jian</ForeName><Initials>BJ</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jin</LastName><ForeName>Dong-Yan</ForeName><Initials>DY</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-2778-3530</Identifier><AffiliationInfo><Affiliation>Department of Biochemistry, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mathieson</LastName><ForeName>Peter W</ForeName><Initials>PW</Initials><AffiliationInfo><Affiliation>Department of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>President's Office, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Qin</LastName><ForeName>Chuan</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences, Chaoyang District, Beijing, 100021, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yuen</LastName><ForeName>Kwok-Yung</ForeName><Initials>KY</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>02</Month><Day>22</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Nat Microbiol</MedlineTA><NlmUniqueID>101674869</NlmUniqueID><ISSNLinking>2058-5276</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C497806">SMAD7 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D051906">Smad7 Protein</NameOfSubstance></Chemical><Chemical><RegistryNumber>103107-01-3</RegistryNumber><NameOfSubstance UI="D016222">Fibroblast Growth Factor 2</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017209" MajorTopicYN="Y">Apoptosis</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002144" MajorTopicYN="N">Callithrix</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018352" MajorTopicYN="N">Coronavirus Infections</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003588" MajorTopicYN="N">Cytopathogenic Effect, Viral</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004195" MajorTopicYN="N">Disease Models, Animal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016222" MajorTopicYN="N">Fibroblast Growth Factor 2</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D054884" MajorTopicYN="N">Host-Pathogen Interactions</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007668" MajorTopicYN="N">Kidney</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008168" MajorTopicYN="N">Lung</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D065207" MajorTopicYN="N">Middle East Respiratory Syndrome Coronavirus</DescriptorName><QualifierName UI="Q000472" MajorTopicYN="Y">pathogenicity</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009924" MajorTopicYN="N">Organ Culture Techniques</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051906" MajorTopicYN="N">Smad7 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IdType="pubmed">12761254</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></pubmed><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Yeung, Man Lung" sort="Yeung, Man Lung" uniqKey="Yeung M" first="Man-Lung" last="Yeung">Man-Lung Yeung</name></noRegion><name sortKey="Chan, Jasper F W" sort="Chan, Jasper F W" uniqKey="Chan J" first="Jasper F W" last="Chan">Jasper F W. Chan</name><name sortKey="Chan, Kwok Hung" sort="Chan, Kwok Hung" uniqKey="Chan K" first="Kwok-Hung" last="Chan">Kwok-Hung Chan</name><name sortKey="Chan, Tak Mao" sort="Chan, Tak Mao" uniqKey="Chan T" first="Tak-Mao" last="Chan">Tak-Mao Chan</name><name sortKey="Chen, Honglin" sort="Chen, Honglin" uniqKey="Chen H" first="Honglin" last="Chen">Honglin Chen</name><name sortKey="Cheung, Kwok Fan" sort="Cheung, Kwok Fan" uniqKey="Cheung K" first="Kwok-Fan" last="Cheung">Kwok-Fan Cheung</name><name sortKey="Chu, Hin" sort="Chu, Hin" uniqKey="Chu H" first="Hin" last="Chu">Hin Chu</name><name sortKey="Deng, Wei" sort="Deng, Wei" uniqKey="Deng W" first="Wei" last="Deng">Wei Deng</name><name sortKey="Jia, Lilong" sort="Jia, Lilong" uniqKey="Jia L" first="Lilong" last="Jia">Lilong Jia</name><name sortKey="Jin, Dong Yan" sort="Jin, Dong Yan" uniqKey="Jin D" first="Dong-Yan" last="Jin">Dong-Yan Jin</name><name sortKey="Lau, Johnson Y N" sort="Lau, Johnson Y N" uniqKey="Lau J" first="Johnson Y N" last="Lau">Johnson Y N. Lau</name><name sortKey="Lau, Susanna K P" sort="Lau, Susanna K P" uniqKey="Lau S" first="Susanna K P" last="Lau">Susanna K P. Lau</name><name sortKey="Mathieson, Peter W" sort="Mathieson, Peter W" uniqKey="Mathieson P" first="Peter W" last="Mathieson">Peter W. Mathieson</name><name sortKey="Poon, Vincent K M" sort="Poon, Vincent K M" uniqKey="Poon V" first="Vincent K M" last="Poon">Vincent K M. Poon</name><name sortKey="Qin, Chuan" sort="Qin, Chuan" uniqKey="Qin C" first="Chuan" last="Qin">Chuan Qin</name><name sortKey="Teng, Jade L L" sort="Teng, Jade L L" uniqKey="Teng J" first="Jade L L" last="Teng">Jade L L. Teng</name><name sortKey="To, Kelvin K W" sort="To, Kelvin K W" uniqKey="To K" first="Kelvin K W" last="To">Kelvin K W. To</name><name sortKey="Tsang, Alan K L" sort="Tsang, Alan K L" uniqKey="Tsang A" first="Alan K L" last="Tsang">Alan K L. Tsang</name><name sortKey="Woo, Patrick C Y" sort="Woo, Patrick C Y" uniqKey="Woo P" first="Patrick C Y" last="Woo">Patrick C Y. 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