MERS coronavirus induces apoptosis in kidney and lung by upregulating Smad7 and FGF2.
Identifieur interne : 000F90 ( PubMed/Corpus ); précédent : 000F89; suivant : 000F91MERS coronavirus induces apoptosis in kidney and lung by upregulating Smad7 and FGF2.
Auteurs : Man-Lung Yeung ; Yanfeng Yao ; Lilong Jia ; Jasper F W. Chan ; Kwok-Hung Chan ; Kwok-Fan Cheung ; Honglin Chen ; Vincent K M. Poon ; Alan K L. Tsang ; Kelvin K W. To ; Ming-Kwong Yiu ; Jade L L. Teng ; Hin Chu ; Jie Zhou ; Qing Zhang ; Wei Deng ; Susanna K P. Lau ; Johnson Y N. Lau ; Patrick C Y. Woo ; Tak-Mao Chan ; Susan Yung ; Bo-Jian Zheng ; Dong-Yan Jin ; Peter W. Mathieson ; Chuan Qin ; Kwok-Yung YuenSource :
- Nature microbiology [ 2058-5276 ] ; 2016.
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
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pubmed:27572168Le document en format XML
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<affiliation><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Yao, Yanfeng" sort="Yao, Yanfeng" uniqKey="Yao Y" first="Yanfeng" last="Yao">Yanfeng Yao</name>
<affiliation><nlm:affiliation>Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences, Chaoyang District, Beijing, 100021, China.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Jia, Lilong" sort="Jia, Lilong" uniqKey="Jia L" first="Lilong" last="Jia">Lilong Jia</name>
<affiliation><nlm:affiliation>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</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><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Chan, Kwok Hung" sort="Chan, Kwok Hung" uniqKey="Chan K" first="Kwok-Hung" last="Chan">Kwok-Hung Chan</name>
<affiliation><nlm:affiliation>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
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<author><name sortKey="Cheung, Kwok Fan" sort="Cheung, Kwok Fan" uniqKey="Cheung K" first="Kwok-Fan" last="Cheung">Kwok-Fan Cheung</name>
<affiliation><nlm:affiliation>Department of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Chen, Honglin" sort="Chen, Honglin" uniqKey="Chen H" first="Honglin" last="Chen">Honglin Chen</name>
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</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><nlm:affiliation>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</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><nlm:affiliation>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</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>
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</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><nlm:affiliation>Department of Surgery, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</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>
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</affiliation>
</author>
<author><name sortKey="Chu, Hin" sort="Chu, Hin" uniqKey="Chu H" first="Hin" last="Chu">Hin Chu</name>
<affiliation><nlm:affiliation>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Zhou, Jie" sort="Zhou, Jie" uniqKey="Zhou J" first="Jie" last="Zhou">Jie Zhou</name>
<affiliation><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Zhang, Qing" sort="Zhang, Qing" uniqKey="Zhang Q" first="Qing" last="Zhang">Qing Zhang</name>
<affiliation><nlm:affiliation>Department of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Deng, Wei" sort="Deng, Wei" uniqKey="Deng W" first="Wei" last="Deng">Wei Deng</name>
<affiliation><nlm:affiliation>Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences, Chaoyang District, Beijing, 100021, China.</nlm:affiliation>
</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><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</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><nlm:affiliation>Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</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><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</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><nlm:affiliation>Department of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Yung, Susan" sort="Yung, Susan" uniqKey="Yung S" first="Susan" last="Yung">Susan Yung</name>
<affiliation><nlm:affiliation>Department of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</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><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</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><nlm:affiliation>Department of Biochemistry, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</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><nlm:affiliation>Department of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Qin, Chuan" sort="Qin, Chuan" uniqKey="Qin C" first="Chuan" last="Qin">Chuan Qin</name>
<affiliation><nlm:affiliation>Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences, Chaoyang District, Beijing, 100021, China.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name>
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<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><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
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<author><name sortKey="Yao, Yanfeng" sort="Yao, Yanfeng" uniqKey="Yao Y" first="Yanfeng" last="Yao">Yanfeng Yao</name>
<affiliation><nlm:affiliation>Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences, Chaoyang District, Beijing, 100021, China.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Jia, Lilong" sort="Jia, Lilong" uniqKey="Jia L" first="Lilong" last="Jia">Lilong Jia</name>
<affiliation><nlm:affiliation>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</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><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</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><nlm:affiliation>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</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><nlm:affiliation>Department of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
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<author><name sortKey="Chen, Honglin" sort="Chen, Honglin" uniqKey="Chen H" first="Honglin" last="Chen">Honglin Chen</name>
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</affiliation>
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<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><nlm:affiliation>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</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><nlm:affiliation>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</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><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</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><nlm:affiliation>Department of Surgery, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</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><nlm:affiliation>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Chu, Hin" sort="Chu, Hin" uniqKey="Chu H" first="Hin" last="Chu">Hin Chu</name>
<affiliation><nlm:affiliation>Department of Microbiology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Zhou, Jie" sort="Zhou, Jie" uniqKey="Zhou J" first="Jie" last="Zhou">Jie Zhou</name>
<affiliation><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Zhang, Qing" sort="Zhang, Qing" uniqKey="Zhang Q" first="Qing" last="Zhang">Qing Zhang</name>
<affiliation><nlm:affiliation>Department of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Deng, Wei" sort="Deng, Wei" uniqKey="Deng W" first="Wei" last="Deng">Wei Deng</name>
<affiliation><nlm:affiliation>Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences, Chaoyang District, Beijing, 100021, China.</nlm:affiliation>
</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><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</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><nlm:affiliation>Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</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><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</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><nlm:affiliation>Department of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Yung, Susan" sort="Yung, Susan" uniqKey="Yung S" first="Susan" last="Yung">Susan Yung</name>
<affiliation><nlm:affiliation>Department of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</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><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</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><nlm:affiliation>Department of Biochemistry, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</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><nlm:affiliation>Department of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Qin, Chuan" sort="Qin, Chuan" uniqKey="Qin C" first="Chuan" last="Qin">Chuan Qin</name>
<affiliation><nlm:affiliation>Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences, Chaoyang District, Beijing, 100021, China.</nlm:affiliation>
</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><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.</nlm:affiliation>
</affiliation>
</author>
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<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>
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<term>Smad7 Protein</term>
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</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Coronavirus Infections</term>
<term>Kidney</term>
<term>Lung</term>
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<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>
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<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>
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<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>
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