MersV1, Main, Exploration, bibRecord, 001174

MERS coronavirus induces apoptosis in kidney and lung by upregulating Smad7 and FGF2

Identifieur interne : 001174 ( Main/Exploration ); précédent : 001173; suivant : 001175

MERS 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 Yuen

Source :

Nature Microbiology [ 2058-5276 ] ; 2016.

RBID : PMC:7097571

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.

Supplementary information

The online version of this article (doi:10.1038/nmicrobiol.2016.4) contains supplementary material, which is available to authorized users.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7097571

DOI: 10.1038/nmicrobiol.2016.4
PubMed: 27572168
PubMed Central: 7097571

Affiliations:

Le document en format XML

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China</nlm:aff>
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China</nlm:aff>
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China</nlm:aff>
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<author><name sortKey="Mathieson, Peter W" sort="Mathieson, Peter W" uniqKey="Mathieson P" first="Peter W." last="Mathieson">Peter W. Mathieson</name>
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China</nlm:aff>
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<author><name sortKey="Qin, Chuan" sort="Qin, Chuan" uniqKey="Qin C" first="Chuan" last="Qin">Chuan Qin</name>
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Chaoyang District, 100021 Beijing China</nlm:aff>
<wicri:noCountry code="subfield">100021 Beijing China</wicri:noCountry>
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</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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China</nlm:aff>
</affiliation>
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<institution>The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
</institution-wrap>
China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
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China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
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China</nlm:aff>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">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>
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<institution>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
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China</nlm:aff>
</affiliation>
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<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>Department of Microbiology,</institution>
<institution>The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
</institution-wrap>
China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
</institution-wrap>
China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
</institution-wrap>
China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Yao, Yanfeng" sort="Yao, Yanfeng" uniqKey="Yao Y" first="Yanfeng" last="Yao">Yanfeng Yao</name>
<affiliation><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="GRID">grid.482592.0</institution-id>
<institution>Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences,</institution>
</institution-wrap>
Chaoyang District, 100021 Beijing China</nlm:aff>
<wicri:noCountry code="subfield">100021 Beijing China</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Jia, Lilong" sort="Jia, Lilong" uniqKey="Jia L" first="Lilong" last="Jia">Lilong Jia</name>
<affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>Department of Microbiology,</institution>
<institution>The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
</institution-wrap>
China</nlm:aff>
</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:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
</institution-wrap>
China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>Department of Microbiology,</institution>
<institution>The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
</institution-wrap>
China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
</institution-wrap>
China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.194645.b</institution-id>
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<institution>Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
</institution-wrap>
China</nlm:aff>
</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:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>Department of Microbiology,</institution>
<institution>The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
</institution-wrap>
China</nlm:aff>
</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:aff id="Aff6"><institution-wrap><institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>Department of Medicine,</institution>
<institution>The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
</institution-wrap>
China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chen, Honglin" sort="Chen, Honglin" uniqKey="Chen H" first="Honglin" last="Chen">Honglin Chen</name>
<affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
</institution-wrap>
China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>Department of Microbiology,</institution>
<institution>The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
</institution-wrap>
China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
</institution-wrap>
China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
</institution-wrap>
China</nlm:aff>
</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:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>Department of Microbiology,</institution>
<institution>The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
</institution-wrap>
China</nlm:aff>
</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:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>Department of Microbiology,</institution>
<institution>The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
</institution-wrap>
China</nlm:aff>
</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:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
</institution-wrap>
China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>Department of Microbiology,</institution>
<institution>The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
</institution-wrap>
China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
</institution-wrap>
China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
</institution-wrap>
China</nlm:aff>
</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:aff id="Aff7"><institution-wrap><institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>Department of Surgery,</institution>
<institution>The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
</institution-wrap>
China</nlm:aff>
</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:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>Department of Microbiology,</institution>
<institution>The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
</institution-wrap>
China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chu, Hin" sort="Chu, Hin" uniqKey="Chu H" first="Hin" last="Chu">Hin Chu</name>
<affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>Department of Microbiology,</institution>
<institution>The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
</institution-wrap>
China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zhou, Jie" sort="Zhou, Jie" uniqKey="Zhou J" first="Jie" last="Zhou">Jie Zhou</name>
<affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
</institution-wrap>
China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>Department of Microbiology,</institution>
<institution>The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
</institution-wrap>
China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
</institution-wrap>
China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
</institution-wrap>
China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zhang, Qing" sort="Zhang, Qing" uniqKey="Zhang Q" first="Qing" last="Zhang">Qing Zhang</name>
<affiliation><nlm:aff id="Aff6"><institution-wrap><institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>Department of Medicine,</institution>
<institution>The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
</institution-wrap>
China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Deng, Wei" sort="Deng, Wei" uniqKey="Deng W" first="Wei" last="Deng">Wei Deng</name>
<affiliation><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="GRID">grid.482592.0</institution-id>
<institution>Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences,</institution>
</institution-wrap>
Chaoyang District, 100021 Beijing China</nlm:aff>
<wicri:noCountry code="subfield">100021 Beijing China</wicri:noCountry>
</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:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
</institution-wrap>
China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>Department of Microbiology,</institution>
<institution>The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
</institution-wrap>
China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
</institution-wrap>
China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
</institution-wrap>
China</nlm:aff>
</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:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
</institution-wrap>
China</nlm:aff>
</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:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
</institution-wrap>
China</nlm:aff>
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China</nlm:aff>
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</author>
<author><name sortKey="Yung, Susan" sort="Yung, Susan" uniqKey="Yung S" first="Susan" last="Yung">Susan Yung</name>
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China</nlm:aff>
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</author>
<author><name sortKey="Zheng, Bo Jian" sort="Zheng, Bo Jian" uniqKey="Zheng B" first="Bo-Jian" last="Zheng">Bo-Jian Zheng</name>
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<author><name sortKey="Jin, Dong Yan" sort="Jin, Dong Yan" uniqKey="Jin D" first="Dong-Yan" last="Jin">Dong-Yan Jin</name>
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China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mathieson, Peter W" sort="Mathieson, Peter W" uniqKey="Mathieson P" first="Peter W." last="Mathieson">Peter W. Mathieson</name>
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<author><name sortKey="Qin, Chuan" sort="Qin, Chuan" uniqKey="Qin C" first="Chuan" last="Qin">Chuan Qin</name>
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<institution>Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences,</institution>
</institution-wrap>
Chaoyang District, 100021 Beijing China</nlm:aff>
<wicri:noCountry code="subfield">100021 Beijing China</wicri:noCountry>
</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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<institution>Department of Microbiology,</institution>
<institution>The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
</institution-wrap>
China</nlm:aff>
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<affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.194645.b</institution-id>
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<institution>Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
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China</nlm:aff>
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<institution>Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong,</institution>
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China</nlm:aff>
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<series><title level="j">Nature Microbiology</title>
<idno type="eISSN">2058-5276</idno>
<imprint><date when="2016">2016</date>
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<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>
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<term>Protéine Smad7</term>
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<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>
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<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>
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<front><div type="abstract" xml:lang="en"><p id="Par1">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<sup><xref ref-type="bibr" rid="CR1">1</xref>
,<xref ref-type="bibr" rid="CR2">2</xref>
</sup>
. The high incidence of renal failure in MERS is a unique clinical feature not often found in other human coronavirus infections<sup><xref ref-type="bibr" rid="CR3">3</xref>
,<xref ref-type="bibr" rid="CR4">4</xref>
</sup>
. Whether MERS-CoV infects the kidney and how it triggers renal failure are not understood<sup><xref ref-type="bibr" rid="CR5">5</xref>
,<xref ref-type="bibr" rid="CR6">6</xref>
</sup>
. Here, we demonstrated renal infection and apoptotic induction by MERS-CoV in human <italic>ex vivo</italic>
 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.</p>
<sec><title>Supplementary information</title>
<p>The online version of this article (doi:10.1038/nmicrobiol.2016.4) contains supplementary material, which is available to authorized users.</p>
</sec>
</div>
</front>
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<tree><noCountry><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>
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<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. Woo</name>
<name sortKey="Yao, Yanfeng" sort="Yao, Yanfeng" uniqKey="Yao Y" first="Yanfeng" last="Yao">Yanfeng Yao</name>
<name sortKey="Yeung, Man Lung" sort="Yeung, Man Lung" uniqKey="Yeung M" first="Man-Lung" last="Yeung">Man-Lung Yeung</name>
<name sortKey="Yiu, Ming Kwong" sort="Yiu, Ming Kwong" uniqKey="Yiu M" first="Ming-Kwong" last="Yiu">Ming-Kwong Yiu</name>
<name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name>
<name sortKey="Yung, Susan" sort="Yung, Susan" uniqKey="Yung S" first="Susan" last="Yung">Susan Yung</name>
<name sortKey="Zhang, Qing" sort="Zhang, Qing" uniqKey="Zhang Q" first="Qing" last="Zhang">Qing Zhang</name>
<name sortKey="Zheng, Bo Jian" sort="Zheng, Bo Jian" uniqKey="Zheng B" first="Bo-Jian" last="Zheng">Bo-Jian Zheng</name>
<name sortKey="Zhou, Jie" sort="Zhou, Jie" uniqKey="Zhou J" first="Jie" last="Zhou">Jie Zhou</name>
</noCountry>
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Serveur d'exploration MERS

MERS coronavirus induces apoptosis in kidney and lung by upregulating Smad7 and FGF2

MERS coronavirus induces apoptosis in kidney and lung by upregulating Smad7 and FGF2

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	Serveur d'exploration MERS
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