In-vitro renal epithelial cell infection reveals a viral kidney tropism as a potential mechanism for acute renal failure during Middle East Respiratory Syndrome (MERS) Coronavirus infection
Identifieur interne : 000173 ( Pmc/Corpus ); précédent : 000172; suivant : 000174In-vitro renal epithelial cell infection reveals a viral kidney tropism as a potential mechanism for acute renal failure during Middle East Respiratory Syndrome (MERS) Coronavirus infection
Auteurs : Isabella Eckerle ; Marcel A. Müller ; Stephan Kallies ; Daniel N. Gotthardt ; Christian DrostenSource :
- Virology Journal [ 1743-422X ] ; 2013.
Abstract
The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes symptoms similar to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), yet involving an additional component of acute renal failure (ARF) according to several published case reports. Impairment of the kidney is not typically seen in Coronavirus infections. The role of kidney infection in MERS is not understood.
A systematic review of communicated and peer-reviewed case reports revealed differences in descriptions of kidney involvement in MERS versus SARS patients. In particular, ARF in MERS patients occurred considerably earlier after a median time to onset of 11 days (SD ±2,0 days) as opposed to 20 days for SARS, according to the literature.
Epidemiological studies should analyze kidney impairment and its characteristics in MERS-CoV. Virus replication in the kidney with potential shedding in urine might constitute a way of transmission, and could explain untraceable transmission chains leading to new cases. Individual patients might benefit from early induction of renoprotective treatment.
The online version of this article (doi:10.1186/1743-422X-10-359) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1186/1743-422X-10-359
PubMed: 24364985
PubMed Central: 3878046
Links to Exploration step
PMC:3878046Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en"><italic>In-vitro</italic> renal epithelial cell infection reveals a viral kidney tropism as a potential mechanism for acute renal failure during Middle East Respiratory Syndrome (MERS) Coronavirus infection</title><author><name sortKey="Eckerle, Isabella" sort="Eckerle, Isabella" uniqKey="Eckerle I" first="Isabella" last="Eckerle">Isabella Eckerle</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.412102.4</institution-id><institution>Institute of Virology,</institution><institution>University of Bonn Medical Centre,</institution></institution-wrap>Sigmund-Freud-Strasse 25, Bonn, 53127 Germany</nlm:aff></affiliation></author><author><name sortKey="Muller, Marcel A" sort="Muller, Marcel A" uniqKey="Muller M" first="Marcel A" last="Müller">Marcel A. Müller</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.412102.4</institution-id><institution>Institute of Virology,</institution><institution>University of Bonn Medical Centre,</institution></institution-wrap>Sigmund-Freud-Strasse 25, Bonn, 53127 Germany</nlm:aff></affiliation></author><author><name sortKey="Kallies, Stephan" sort="Kallies, Stephan" uniqKey="Kallies S" first="Stephan" last="Kallies">Stephan Kallies</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.412102.4</institution-id><institution>Institute of Virology,</institution><institution>University of Bonn Medical Centre,</institution></institution-wrap>Sigmund-Freud-Strasse 25, Bonn, 53127 Germany</nlm:aff></affiliation></author><author><name sortKey="Gotthardt, Daniel N" sort="Gotthardt, Daniel N" uniqKey="Gotthardt D" first="Daniel N" last="Gotthardt">Daniel N. Gotthardt</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.5253.1</institution-id><institution-id institution-id-type="ISNI">0000000103284908</institution-id><institution>Department of Internal Medicine IV,</institution><institution>University Hospital Heidelberg,</institution></institution-wrap>Im Neuenheimer Feld 410, Heidelberg, 69120 Germany</nlm:aff></affiliation></author><author><name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.412102.4</institution-id><institution>Institute of Virology,</institution><institution>University of Bonn Medical Centre,</institution></institution-wrap>Sigmund-Freud-Strasse 25, Bonn, 53127 Germany</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24364985</idno><idno type="pmc">3878046</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3878046</idno><idno type="RBID">PMC:3878046</idno><idno type="doi">10.1186/1743-422X-10-359</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">000173</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000173</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main"><italic>In-vitro</italic> renal epithelial cell infection reveals a viral kidney tropism as a potential mechanism for acute renal failure during Middle East Respiratory Syndrome (MERS) Coronavirus infection</title><author><name sortKey="Eckerle, Isabella" sort="Eckerle, Isabella" uniqKey="Eckerle I" first="Isabella" last="Eckerle">Isabella Eckerle</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.412102.4</institution-id><institution>Institute of Virology,</institution><institution>University of Bonn Medical Centre,</institution></institution-wrap>Sigmund-Freud-Strasse 25, Bonn, 53127 Germany</nlm:aff></affiliation></author><author><name sortKey="Muller, Marcel A" sort="Muller, Marcel A" uniqKey="Muller M" first="Marcel A" last="Müller">Marcel A. Müller</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.412102.4</institution-id><institution>Institute of Virology,</institution><institution>University of Bonn Medical Centre,</institution></institution-wrap>Sigmund-Freud-Strasse 25, Bonn, 53127 Germany</nlm:aff></affiliation></author><author><name sortKey="Kallies, Stephan" sort="Kallies, Stephan" uniqKey="Kallies S" first="Stephan" last="Kallies">Stephan Kallies</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.412102.4</institution-id><institution>Institute of Virology,</institution><institution>University of Bonn Medical Centre,</institution></institution-wrap>Sigmund-Freud-Strasse 25, Bonn, 53127 Germany</nlm:aff></affiliation></author><author><name sortKey="Gotthardt, Daniel N" sort="Gotthardt, Daniel N" uniqKey="Gotthardt D" first="Daniel N" last="Gotthardt">Daniel N. Gotthardt</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.5253.1</institution-id><institution-id institution-id-type="ISNI">0000000103284908</institution-id><institution>Department of Internal Medicine IV,</institution><institution>University Hospital Heidelberg,</institution></institution-wrap>Im Neuenheimer Feld 410, Heidelberg, 69120 Germany</nlm:aff></affiliation></author><author><name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.412102.4</institution-id><institution>Institute of Virology,</institution><institution>University of Bonn Medical Centre,</institution></institution-wrap>Sigmund-Freud-Strasse 25, Bonn, 53127 Germany</nlm:aff></affiliation></author></analytic><series><title level="j">Virology Journal</title><idno type="eISSN">1743-422X</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes symptoms similar to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), yet involving an additional component of acute renal failure (ARF) according to several published case reports. Impairment of the kidney is not typically seen in Coronavirus infections. The role of kidney infection in MERS is not understood.</p></sec><sec><title>Findings</title><p>A systematic review of communicated and peer-reviewed case reports revealed differences in descriptions of kidney involvement in MERS versus SARS patients. In particular, ARF in MERS patients occurred considerably earlier after a median time to onset of 11 days (SD ±2,0 days) as opposed to 20 days for SARS, according to the literature. <italic>In-situ</italic> histological staining of the respective cellular receptors for MERS- and SARS-Coronavirus showed highly similar staining patterns with a focus of a receptor-specific signal in kidney epithelial cells. Comparative infection experiments with SARS- and MERS-CoV in primary human kidney cells versus primary human bronchial epithelial cells showed cytopathogenic infection only in kidney cells, and only if infected with MERS-CoV. Kidney epithelial cells produced almost 1000-fold more infectious MERS-CoV progeny than bronchial epithelial cells, while only a small difference was seen between cell types when infected with SARS-CoV.</p></sec><sec><title>Conclusion</title><p>Epidemiological studies should analyze kidney impairment and its characteristics in MERS-CoV. Virus replication in the kidney with potential shedding in urine might constitute a way of transmission, and could explain untraceable transmission chains leading to new cases. Individual patients might benefit from early induction of renoprotective treatment.</p></sec><sec><title>Electronic supplementary material</title><p>The online version of this article (doi:10.1186/1743-422X-10-359) contains supplementary material, which is available to authorized users.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Peiris, Js" uniqKey="Peiris J">JS Peiris</name></author><author><name sortKey="Guan, Y" uniqKey="Guan Y">Y Guan</name></author><author><name sortKey="Yuen, Ky" uniqKey="Yuen K">KY Yuen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zaki, Am" uniqKey="Zaki A">AM Zaki</name></author><author><name sortKey="Van Boheemen, S" uniqKey="Van Boheemen S">S van Boheemen</name></author><author><name sortKey="Bestebroer, Tm" uniqKey="Bestebroer T">TM Bestebroer</name></author><author><name sortKey="Osterhaus, Ad" uniqKey="Osterhaus A">AD Osterhaus</name></author><author><name sortKey="Fouchier, Ra" uniqKey="Fouchier R">RA Fouchier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Memish, Za" uniqKey="Memish Z">ZA Memish</name></author><author><name sortKey="Zumla, Ai" uniqKey="Zumla A">AI Zumla</name></author><author><name sortKey="Al Hakeem, Rf" uniqKey="Al Hakeem R">RF Al-Hakeem</name></author><author><name sortKey="Al Rabeeah, Aa" uniqKey="Al Rabeeah A">AA Al-Rabeeah</name></author><author><name sortKey="Stephens, Gm" uniqKey="Stephens G">GM Stephens</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Assiri, A" uniqKey="Assiri A">A Assiri</name></author><author><name sortKey="Mcgeer, A" uniqKey="Mcgeer A">A McGeer</name></author><author><name sortKey="Perl, Tm" uniqKey="Perl T">TM Perl</name></author><author><name sortKey="Price, Cs" uniqKey="Price C">CS Price</name></author><author><name sortKey="Al Rabeeah, Aa" uniqKey="Al Rabeeah A">AA Al Rabeeah</name></author><author><name sortKey="Cummings, Da" uniqKey="Cummings D">DA Cummings</name></author><author><name sortKey="Alabdullatif, Zn" uniqKey="Alabdullatif Z">ZN Alabdullatif</name></author><author><name sortKey="Assad, M" uniqKey="Assad M">M Assad</name></author><author><name sortKey="Almulhim, A" uniqKey="Almulhim A">A Almulhim</name></author><author><name sortKey="Makhdoom, H" uniqKey="Makhdoom H">H Makhdoom</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Drosten, C" uniqKey="Drosten C">C Drosten</name></author><author><name sortKey="Seilmaier, M" uniqKey="Seilmaier M">M Seilmaier</name></author><author><name sortKey="Corman, Vm" uniqKey="Corman V">VM Corman</name></author><author><name sortKey="Hartmann, W" uniqKey="Hartmann W">W Hartmann</name></author><author><name sortKey="Scheible, G" uniqKey="Scheible G">G Scheible</name></author><author><name sortKey="Sack, S" uniqKey="Sack S">S Sack</name></author><author><name sortKey="Guggemos, W" uniqKey="Guggemos W">W Guggemos</name></author><author><name sortKey="Kallies, R" uniqKey="Kallies R">R Kallies</name></author><author><name sortKey="Muth, D" uniqKey="Muth D">D Muth</name></author><author><name sortKey="Junglen, S" uniqKey="Junglen S">S Junglen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Guery, B" uniqKey="Guery B">B Guery</name></author><author><name sortKey="Poissy, J" uniqKey="Poissy J">J Poissy</name></author><author><name sortKey="El Mansouf, L" uniqKey="El Mansouf L">L el Mansouf</name></author><author><name sortKey="Sejourne, C" uniqKey="Sejourne C">C Sejourne</name></author><author><name sortKey="Ettahar, N" uniqKey="Ettahar N">N Ettahar</name></author><author><name sortKey="Lemaire, X" uniqKey="Lemaire X">X Lemaire</name></author><author><name sortKey="Vuotto, F" uniqKey="Vuotto F">F Vuotto</name></author><author><name sortKey="Goffard, A" uniqKey="Goffard A">A Goffard</name></author><author><name sortKey="Behillil, S" uniqKey="Behillil S">S Behillil</name></author><author><name sortKey="Enouf, V" uniqKey="Enouf V">V Enouf</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pollack, Mp" uniqKey="Pollack M">MP Pollack</name></author><author><name sortKey="Pringle, C" uniqKey="Pringle C">C Pringle</name></author><author><name sortKey="Madoff, Lc" uniqKey="Madoff L">LC Madoff</name></author><author><name sortKey="Memish, Za" uniqKey="Memish Z">ZA Memish</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Muller, Ma" uniqKey="Muller M">MA Muller</name></author><author><name sortKey="Raj, Vs" uniqKey="Raj V">VS Raj</name></author><author><name sortKey="Muth, D" uniqKey="Muth D">D Muth</name></author><author><name sortKey="Meyer, B" uniqKey="Meyer B">B Meyer</name></author><author><name sortKey="Kallies, S" uniqKey="Kallies S">S Kallies</name></author><author><name sortKey="Smits, Sl" uniqKey="Smits S">SL Smits</name></author><author><name sortKey="Wollny, R" uniqKey="Wollny R">R Wollny</name></author><author><name sortKey="Bestebroer, Tm" uniqKey="Bestebroer T">TM Bestebroer</name></author><author><name sortKey="Specht, S" uniqKey="Specht S">S Specht</name></author><author><name sortKey="Suliman, T" uniqKey="Suliman T">T Suliman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Raj, Vs" uniqKey="Raj V">VS Raj</name></author><author><name sortKey="Mou, H" uniqKey="Mou H">H Mou</name></author><author><name sortKey="Smits, Sl" uniqKey="Smits S">SL Smits</name></author><author><name sortKey="Dekkers, Dh" uniqKey="Dekkers D">DH Dekkers</name></author><author><name sortKey="Muller, Ma" uniqKey="Muller M">MA Muller</name></author><author><name sortKey="Dijkman, R" uniqKey="Dijkman R">R Dijkman</name></author><author><name sortKey="Muth, D" uniqKey="Muth D">D Muth</name></author><author><name sortKey="Demmers, Ja" uniqKey="Demmers J">JA Demmers</name></author><author><name sortKey="Zaki, A" uniqKey="Zaki A">A Zaki</name></author><author><name sortKey="Fouchier, Ra" uniqKey="Fouchier R">RA Fouchier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hamming, I" uniqKey="Hamming I">I Hamming</name></author><author><name sortKey="Cooper, Me" uniqKey="Cooper M">ME Cooper</name></author><author><name sortKey="Haagmans, Bl" uniqKey="Haagmans B">BL Haagmans</name></author><author><name sortKey="Hooper, Nm" uniqKey="Hooper N">NM Hooper</name></author><author><name sortKey="Korstanje, R" uniqKey="Korstanje R">R Korstanje</name></author><author><name sortKey="Osterhaus, Ad" uniqKey="Osterhaus A">AD Osterhaus</name></author><author><name sortKey="Timens, W" uniqKey="Timens W">W Timens</name></author><author><name sortKey="Turner, Aj" uniqKey="Turner A">AJ Turner</name></author><author><name sortKey="Navis, G" uniqKey="Navis G">G Navis</name></author><author><name sortKey="Van Goor, H" uniqKey="Van Goor H">H van Goor</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lambeir, Am" uniqKey="Lambeir A">AM Lambeir</name></author><author><name sortKey="Durinx, C" uniqKey="Durinx C">C Durinx</name></author><author><name sortKey="Scharpe, S" uniqKey="Scharpe S">S Scharpe</name></author><author><name sortKey="De Meester, I" uniqKey="De Meester I">I De Meester</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Groot, Rj" uniqKey="De Groot R">RJ de Groot</name></author><author><name sortKey="Baker, Sc" uniqKey="Baker S">SC Baker</name></author><author><name sortKey="Baric, Rs" uniqKey="Baric R">RS Baric</name></author><author><name sortKey="Brown, Cs" uniqKey="Brown C">CS Brown</name></author><author><name sortKey="Drosten, C" uniqKey="Drosten C">C Drosten</name></author><author><name sortKey="Enjuanes, L" uniqKey="Enjuanes L">L Enjuanes</name></author><author><name sortKey="Fouchier, Ra" uniqKey="Fouchier R">RA Fouchier</name></author><author><name sortKey="Galiano, M" uniqKey="Galiano M">M Galiano</name></author><author><name sortKey="Gorbalenya, Ae" uniqKey="Gorbalenya A">AE Gorbalenya</name></author><author><name sortKey="Memish, Za" uniqKey="Memish Z">ZA Memish</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Buchholz, U" uniqKey="Buchholz U">U Buchholz</name></author><author><name sortKey="Muller, Ma" uniqKey="Muller M">MA Muller</name></author><author><name sortKey="Nitsche, A" uniqKey="Nitsche A">A Nitsche</name></author><author><name sortKey="Sanewski, A" uniqKey="Sanewski A">A Sanewski</name></author><author><name sortKey="Wevering, N" uniqKey="Wevering N">N Wevering</name></author><author><name sortKey="Bauer Balci, T" uniqKey="Bauer Balci T">T Bauer-Balci</name></author><author><name sortKey="Bonin, F" uniqKey="Bonin F">F Bonin</name></author><author><name sortKey="Drosten, C" uniqKey="Drosten C">C Drosten</name></author><author><name sortKey="Schweiger, B" uniqKey="Schweiger B">B Schweiger</name></author><author><name sortKey="Wolff, T" uniqKey="Wolff T">T Wolff</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bermingham, A" uniqKey="Bermingham A">A Bermingham</name></author><author><name sortKey="Chand, Ma" uniqKey="Chand M">MA Chand</name></author><author><name sortKey="Brown, Cs" uniqKey="Brown C">CS Brown</name></author><author><name sortKey="Aarons, E" uniqKey="Aarons E">E Aarons</name></author><author><name sortKey="Tong, C" uniqKey="Tong C">C Tong</name></author><author><name sortKey="Langrish, C" uniqKey="Langrish C">C Langrish</name></author><author><name sortKey="Hoschler, K" uniqKey="Hoschler K">K Hoschler</name></author><author><name sortKey="Brown, K" uniqKey="Brown K">K Brown</name></author><author><name sortKey="Galiano, M" uniqKey="Galiano M">M Galiano</name></author><author><name sortKey="Myers, R" uniqKey="Myers R">R Myers</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Corman, Vm" uniqKey="Corman V">VM Corman</name></author><author><name sortKey="Eckerle, I" uniqKey="Eckerle I">I Eckerle</name></author><author><name sortKey="Bleicker, T" uniqKey="Bleicker T">T Bleicker</name></author><author><name sortKey="Zaki, A" uniqKey="Zaki A">A Zaki</name></author><author><name sortKey="Landt, O" uniqKey="Landt O">O Landt</name></author><author><name sortKey="Eschbach Bludau, M" uniqKey="Eschbach Bludau M">M Eschbach-Bludau</name></author><author><name sortKey="Van Boheemen, S" uniqKey="Van Boheemen S">S van Boheemen</name></author><author><name sortKey="Gopal, R" uniqKey="Gopal R">R Gopal</name></author><author><name sortKey="Ballhause, M" uniqKey="Ballhause M">M Ballhause</name></author><author><name sortKey="Bestebroer, Tm" uniqKey="Bestebroer T">TM Bestebroer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chu, Kh" uniqKey="Chu K">KH Chu</name></author><author><name sortKey="Tsang, Wk" uniqKey="Tsang W">WK Tsang</name></author><author><name sortKey="Tang, Cs" uniqKey="Tang C">CS Tang</name></author><author><name sortKey="Lam, Mf" uniqKey="Lam M">MF Lam</name></author><author><name sortKey="Lai, Fm" uniqKey="Lai F">FM Lai</name></author><author><name sortKey="To, Kf" uniqKey="To K">KF To</name></author><author><name sortKey="Fung, Ks" uniqKey="Fung K">KS Fung</name></author><author><name sortKey="Tang, Hl" uniqKey="Tang H">HL Tang</name></author><author><name sortKey="Yan, Ww" uniqKey="Yan W">WW Yan</name></author><author><name sortKey="Chan, Hw" uniqKey="Chan H">HW Chan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Falzarano, D" uniqKey="Falzarano D">D Falzarano</name></author><author><name sortKey="De Wit, E" uniqKey="De Wit E">E de Wit</name></author><author><name sortKey="Rasmussen, Al" uniqKey="Rasmussen A">AL Rasmussen</name></author><author><name sortKey="Feldmann, F" uniqKey="Feldmann F">F Feldmann</name></author><author><name sortKey="Okumura, A" uniqKey="Okumura A">A Okumura</name></author><author><name sortKey="Scott, Dp" uniqKey="Scott D">DP Scott</name></author><author><name sortKey="Brining, D" uniqKey="Brining D">D Brining</name></author><author><name sortKey="Bushmaker, T" uniqKey="Bushmaker T">T Bushmaker</name></author><author><name sortKey="Martellaro, C" uniqKey="Martellaro C">C Martellaro</name></author><author><name sortKey="Baseler, L" uniqKey="Baseler L">L Baseler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Munster, Vj" uniqKey="Munster V">VJ Munster</name></author><author><name sortKey="De Wit, E" uniqKey="De Wit E">E de Wit</name></author><author><name sortKey="Feldmann, H" uniqKey="Feldmann H">H Feldmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Wit, E" uniqKey="De Wit E">E de Wit</name></author><author><name sortKey="Rasmussen, Al" uniqKey="Rasmussen A">AL Rasmussen</name></author><author><name sortKey="Falzarano, D" uniqKey="Falzarano D">D Falzarano</name></author><author><name sortKey="Bushmaker, T" uniqKey="Bushmaker T">T Bushmaker</name></author><author><name sortKey="Feldmann, F" uniqKey="Feldmann F">F Feldmann</name></author><author><name sortKey="Brining, Dl" uniqKey="Brining D">DL Brining</name></author><author><name sortKey="Fischer, Er" uniqKey="Fischer E">ER Fischer</name></author><author><name sortKey="Martellaro, C" uniqKey="Martellaro C">C Martellaro</name></author><author><name sortKey="Okumura, A" uniqKey="Okumura A">A Okumura</name></author><author><name sortKey="Chang, J" uniqKey="Chang J">J Chang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tang, Jw" uniqKey="Tang J">JW Tang</name></author><author><name sortKey="To, Kf" uniqKey="To K">KF To</name></author><author><name sortKey="Lo, Aw" uniqKey="Lo A">AW Lo</name></author><author><name sortKey="Sung, Jj" uniqKey="Sung J">JJ Sung</name></author><author><name sortKey="Ng, Hk" uniqKey="Ng H">HK Ng</name></author><author><name sortKey="Chan, Pk" uniqKey="Chan P">PK Chan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pacciarini, F" uniqKey="Pacciarini F">F Pacciarini</name></author><author><name sortKey="Ghezzi, S" uniqKey="Ghezzi S">S Ghezzi</name></author><author><name sortKey="Canducci, F" uniqKey="Canducci F">F Canducci</name></author><author><name sortKey="Sims, A" uniqKey="Sims A">A Sims</name></author><author><name sortKey="Sampaolo, M" uniqKey="Sampaolo M">M Sampaolo</name></author><author><name sortKey="Ferioli, E" uniqKey="Ferioli E">E Ferioli</name></author><author><name sortKey="Clementi, M" uniqKey="Clementi M">M Clementi</name></author><author><name sortKey="Poli, G" uniqKey="Poli G">G Poli</name></author><author><name sortKey="Conaldi, Pg" uniqKey="Conaldi P">PG Conaldi</name></author><author><name sortKey="Baric, R" uniqKey="Baric R">R Baric</name></author><author><name sortKey="Vicenzi, E" uniqKey="Vicenzi E">E Vicenzi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Niemeyer, D" uniqKey="Niemeyer D">D Niemeyer</name></author><author><name sortKey="Zillinger, T" uniqKey="Zillinger T">T Zillinger</name></author><author><name sortKey="Muth, D" uniqKey="Muth D">D Muth</name></author><author><name sortKey="Zielecki, F" uniqKey="Zielecki F">F Zielecki</name></author><author><name sortKey="Horvath, G" uniqKey="Horvath G">G Horvath</name></author><author><name sortKey="Suliman, T" uniqKey="Suliman T">T Suliman</name></author><author><name sortKey="Barchet, W" uniqKey="Barchet W">W Barchet</name></author><author><name sortKey="Weber, F" uniqKey="Weber F">F Weber</name></author><author><name sortKey="Drosten, C" uniqKey="Drosten C">C Drosten</name></author><author><name sortKey="Muller, Ma" uniqKey="Muller M">MA Muller</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Goh, Gk" uniqKey="Goh G">GK Goh</name></author><author><name sortKey="Dunker, Ak" uniqKey="Dunker A">AK Dunker</name></author><author><name sortKey="Uversky, V" uniqKey="Uversky V">V Uversky</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="case-report"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Virol J</journal-id><journal-id journal-id-type="iso-abbrev">Virol. J</journal-id><journal-title-group><journal-title>Virology Journal</journal-title></journal-title-group><issn pub-type="epub">1743-422X</issn><publisher><publisher-name>BioMed Central</publisher-name><publisher-loc>London</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">24364985</article-id><article-id pub-id-type="pmc">3878046</article-id><article-id pub-id-type="publisher-id">2343</article-id><article-id pub-id-type="doi">10.1186/1743-422X-10-359</article-id><article-categories><subj-group subj-group-type="heading"><subject>Short Report</subject></subj-group></article-categories><title-group><article-title><italic>In-vitro</italic> renal epithelial cell infection reveals a viral kidney tropism as a potential mechanism for acute renal failure during Middle East Respiratory Syndrome (MERS) Coronavirus infection</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Eckerle</surname><given-names>Isabella</given-names></name><address><email>eckerle@virology-bonn.de</email></address><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Müller</surname><given-names>Marcel A</given-names></name><address><email>muller@virology-bonn.de</email></address><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Kallies</surname><given-names>Stephan</given-names></name><address><email>kallies@virology-bonn.de</email></address><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Gotthardt</surname><given-names>Daniel N</given-names></name><address><email>daniel.gotthardt@med.uni-heidelberg.de</email></address><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Drosten</surname><given-names>Christian</given-names></name><address><email>drosten@virology-bonn.de</email></address><xref ref-type="aff" rid="Aff1">1</xref></contrib><aff id="Aff1"><label>1</label><institution-wrap><institution-id institution-id-type="GRID">grid.412102.4</institution-id><institution>Institute of Virology,</institution><institution>University of Bonn Medical Centre,</institution></institution-wrap>Sigmund-Freud-Strasse 25, Bonn, 53127 Germany</aff><aff id="Aff2"><label>2</label><institution-wrap><institution-id institution-id-type="GRID">grid.5253.1</institution-id><institution-id institution-id-type="ISNI">0000000103284908</institution-id><institution>Department of Internal Medicine IV,</institution><institution>University Hospital Heidelberg,</institution></institution-wrap>Im Neuenheimer Feld 410, Heidelberg, 69120 Germany</aff></contrib-group><pub-date pub-type="epub"><day>23</day><month>12</month><year>2013</year></pub-date><pub-date pub-type="pmc-release"><day>23</day><month>12</month><year>2013</year></pub-date><pub-date pub-type="collection"><year>2013</year></pub-date><volume>10</volume><elocation-id>359</elocation-id><history><date date-type="received"><day>17</day><month>10</month><year>2013</year></date><date date-type="accepted"><day>13</day><month>12</month><year>2013</year></date></history><permissions><copyright-statement>© Eckerle et al.; licensee BioMed Central Ltd. 2013</copyright-statement><license><license-p>This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.</license-p></license></permissions><abstract id="Abs1"><sec><title>Background</title><p>The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes symptoms similar to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), yet involving an additional component of acute renal failure (ARF) according to several published case reports. Impairment of the kidney is not typically seen in Coronavirus infections. The role of kidney infection in MERS is not understood.</p></sec><sec><title>Findings</title><p>A systematic review of communicated and peer-reviewed case reports revealed differences in descriptions of kidney involvement in MERS versus SARS patients. In particular, ARF in MERS patients occurred considerably earlier after a median time to onset of 11 days (SD ±2,0 days) as opposed to 20 days for SARS, according to the literature. <italic>In-situ</italic> histological staining of the respective cellular receptors for MERS- and SARS-Coronavirus showed highly similar staining patterns with a focus of a receptor-specific signal in kidney epithelial cells. Comparative infection experiments with SARS- and MERS-CoV in primary human kidney cells versus primary human bronchial epithelial cells showed cytopathogenic infection only in kidney cells, and only if infected with MERS-CoV. Kidney epithelial cells produced almost 1000-fold more infectious MERS-CoV progeny than bronchial epithelial cells, while only a small difference was seen between cell types when infected with SARS-CoV.</p></sec><sec><title>Conclusion</title><p>Epidemiological studies should analyze kidney impairment and its characteristics in MERS-CoV. Virus replication in the kidney with potential shedding in urine might constitute a way of transmission, and could explain untraceable transmission chains leading to new cases. Individual patients might benefit from early induction of renoprotective treatment.</p></sec><sec><title>Electronic supplementary material</title><p>The online version of this article (doi:10.1186/1743-422X-10-359) contains supplementary material, which is available to authorized users.</p></sec></abstract><kwd-group xml:lang="en"><title>Keywords</title><kwd>Middle East Respiratory Syndrome</kwd><kwd>Acute renal failure</kwd><kwd>Human Coronavirus</kwd><kwd>Renal epithelial cells</kwd><kwd>Dipeptidyl-peptidase-4</kwd><kwd>Angiotensin-converting-enzyme-2</kwd></kwd-group><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© The Author(s) 2013</meta-value></custom-meta></custom-meta-group></article-meta></front><body><p>Coronaviruses (CoVs) cause human disease with symptoms ranging from mild respiratory symptoms to severe pneumonia [<xref ref-type="bibr" rid="CR1">1</xref>]. In September 2012, a novel CoV termed the Middle East Respiratory Syndrome (MERS)-CoV emerged on the Arabian Peninsula with 163 laboratory-confirmed cases including 71 deaths so far (World Health Organization, December 2nd, <ext-link ext-link-type="uri" xlink:href="http://www.who.int/csr/don/2013_12_02/en/index.html">http://www.who.int/csr/don/2013_12_02/en/index.html</ext-link>). Due to its distribution in several countries of the Arabian Peninsula there is a risk of global spread through travel and pilgrimage, posing a potential threat to global public health.</p><p>The clinical picture of MERS-CoV infection is characterized by acute atypical pneumonia and respiratory failure, resembling symptoms caused by SARS-CoV [<xref ref-type="bibr" rid="CR2">2</xref>–<xref ref-type="bibr" rid="CR5">5</xref>]. Acute renal failure (ARF) was described in a number of MERS cases, with potential influence on disease severity [<xref ref-type="bibr" rid="CR2">2</xref>, <xref ref-type="bibr" rid="CR3">3</xref>, <xref ref-type="bibr" rid="CR5">5</xref>–<xref ref-type="bibr" rid="CR7">7</xref>]. ARF has neither been a typical feature of SARS, nor has it been commonly observed in infections caused by any other CoV, including human HCoV-NL63, -229E, –OC43, and -HKU1. Of note, the majority (76%) of MERS-CoV patients were reportred to have underlying medical conditions such as diabetes, chronic cardiac disease and chronic renal disease [<xref ref-type="bibr" rid="CR4">4</xref>, <xref ref-type="bibr" rid="CR8">8</xref>].</p><p>It has been shown recently that MERS-CoV enters target cells not via the SARS-CoV receptor Angiotensin-converting-enzyme-2 (ACE-2), but via binding to Dipeptidyl-peptidase 4 (DPP-4) [<xref ref-type="bibr" rid="CR9">9</xref>, <xref ref-type="bibr" rid="CR10">10</xref>]. Both, ACE-2 and DPP-4 are expressed in several human tissues, including the kidney [<xref ref-type="bibr" rid="CR11">11</xref>, <xref ref-type="bibr" rid="CR12">12</xref>]. However, kidney infection has not been compared between MERS-CoV and SARS-CoV, and no post-mortem investigations on patients who succumbed to MERS-CoV have been done. To assess the potential role of kidney affection in MERS-CoV infection, we reviewed all peer-reviewed or communicated reports on MERS cases for information on kidney involvement. The search was performed in PubMed and Promed.Mail (<ext-link ext-link-type="uri" xlink:href="http://www.promedmail.org">http://www.promedmail.org</ext-link>) using the search term “coronavirus” on items published between 15th September 2012 and 16th September 2013. The broad search term was chosen due to inconsistencies of nomenclature before the consensus name MERS-CoV was announced [<xref ref-type="bibr" rid="CR13">13</xref>].</p><p>In total, the search revealed 655 publications, including 508 articles in PubMed, and 147 reports in ProMed (Figure <xref rid="Fig1" ref-type="fig">1</xref>). All identified publications were reviewed in order to identify clinical descriptions of MERS-CoV infection that included information on kidney function, irrespective of whether they were pointing to normal or impaired function. In cases where two reports on the same patient were available, only the report with the more detailed clinical description was selected. From all identified reports, we extracted information on patient sex and age, country of patient origin and travel route, onset of illness, presence or absence of ARF, date of onset of ARF, day of illness on which ARF occurred, as well as clinical outcome (death or survival). Among 21 publications describing a total of 111 MERS-CoV patients (double-reporting of the same patients could not be excluded), a total of 7 publications were identified that specifically addressed kidney function [<xref ref-type="bibr" rid="CR2">2</xref>, <xref ref-type="bibr" rid="CR3">3</xref>, <xref ref-type="bibr" rid="CR5">5</xref>–<xref ref-type="bibr" rid="CR7">7</xref>, <xref ref-type="bibr" rid="CR14">14</xref>, <xref ref-type="bibr" rid="CR15">15</xref>]. In these 7 publications, a total of 12 MERS patients were described with disease onset dates ranging from April 2012 to March 2013 (Table <xref rid="Tab1" ref-type="table">1</xref>). All patients were male with a mean age of 47 years (range 25–73 years), originating from Jordan, Saudi Arabia, and Qatar, including imported cases to the United Kingdom (UK), Germany and France. Nine of those 12 patients (75%) developed ARF during the acute course of MERS-CoV infection. For 6 of those 9 patients, dates of onset of ARF were available, suggesting a median time of 11 days (SD ±2,0 days) from first symptoms to onset of ARF. Six of 9 (67%) patients with ARF had a fatal outcome, while one of three patients without ARF died. However, the differences found for the fatality rates in cases with and without ARF during MERS-CoV infection were not statistically significant.<fig id="Fig1"><label>Figure 1</label><caption><p><bold>Flowchart of study selection.</bold> Systematic search strategies were applied to identify all reports on patients’ kidney function during MERS-CoV infection. Data sources used were Pubmed (<ext-link ext-link-type="uri" xlink:href="http://www.ncbi.nlm.nih.gov/pubmed/">http://www.ncbi.nlm.nih.gov/pubmed/</ext-link>) and Promed.Mail (<ext-link ext-link-type="uri" xlink:href="http://www.promedmail.org">http://www.promedmail.org</ext-link>) by searching the term “coronavirus” with a date range from 15th September 2012 (date of the first MERS-CoV report) to 16th September 2013. All identified publications were reviewed for clinical data on kidney function (irrespective of pointing to normal or impaired function). Data on patient sex and age, country of patient origin and travel route, onset of illness, presence or absence of ARF, date of onset of ARF, day of illness on which ARF occurred, as well as clinical outcome (death or survival) were extracted. In total, 7 publications were finally included that described a total of 12 MERS-CoV patients and their kidney function during the course of disease.</p></caption><graphic xlink:href="12985_2013_Article_2343_Fig1_HTML" id="d29e383"></graphic></fig></p><table-wrap id="Tab1"><label>Table 1</label><caption><p><bold>MERS-CoV patients with explicit reports on presence or absence of acute renal failure (ARF)</bold></p></caption><table frame="hsides" rules="groups"><thead><tr><th>Nr.</th><th>Patient</th><th>Country</th><th>Onset of illness</th><th>ARF</th><th>Onset ARF</th><th>ARF on day of illness</th><th>Outcome</th><th>Reference</th></tr></thead><tbody><tr><td>1</td><td>25 y m</td><td>Jordan</td><td>Apr 12, day nd</td><td>Yes</td><td>nd</td><td>nd</td><td>Fatal</td><td>[<xref ref-type="bibr" rid="CR7">7</xref>]</td></tr><tr><td>2</td><td>60 y m</td><td>Saudi Arabia</td><td>7 Jun 12</td><td>Yes</td><td>16 Jun 12</td><td>10</td><td>Fatal</td><td>[<xref ref-type="bibr" rid="CR2">2</xref>]</td></tr><tr><td>3</td><td>49 y m</td><td>UK ex Qatar</td><td>3 Sep 12</td><td>Yes</td><td>14 Sep 12</td><td>12</td><td>Fatal</td><td>[<xref ref-type="bibr" rid="CR15">15</xref>]</td></tr><tr><td>4</td><td>45 y m</td><td>Saudi Arabia</td><td>Nov 12, day nd</td><td>Yes</td><td>nd</td><td>nd</td><td>Recovered</td><td>[<xref ref-type="bibr" rid="CR7">7</xref>]</td></tr><tr><td>5</td><td>45 y m</td><td>Germany ex Qatar</td><td>5 Oct 12</td><td>Yes</td><td>nd</td><td>nd</td><td>Recovered</td><td>[<xref ref-type="bibr" rid="CR14">14</xref>]</td></tr><tr><td>6</td><td>70 y m</td><td>Saudi Arabia</td><td>5 Oct 12</td><td>Yes</td><td>16 Oct 12</td><td>12</td><td>Fatal</td><td>[<xref ref-type="bibr" rid="CR3">3</xref>]</td></tr><tr><td>7</td><td>39 y m</td><td>Saudi Arabia</td><td>24 Oct 12</td><td>No</td><td>-</td><td></td><td>Fatal</td><td>[<xref ref-type="bibr" rid="CR3">3</xref>]</td></tr><tr><td>8</td><td>16 y m</td><td>Saudi Arabia</td><td>3 Nov 12</td><td>No</td><td>-</td><td></td><td>Recovered</td><td>[<xref ref-type="bibr" rid="CR3">3</xref>]</td></tr><tr><td>9</td><td>31 y m</td><td>Saudi Arabia</td><td>4 Nov 12</td><td>No</td><td>-</td><td></td><td>Recovered</td><td>[<xref ref-type="bibr" rid="CR3">3</xref>]</td></tr><tr><td>10</td><td>64 y m</td><td>France ex Saudi Arabia</td><td>22 Apr 13</td><td>Yes</td><td>30 Apr 13</td><td>9</td><td>Fatal</td><td>[<xref ref-type="bibr" rid="CR6">6</xref>]</td></tr><tr><td>11</td><td>51 y m</td><td>France</td><td>8 May 13</td><td>Yes</td><td>14 May 13</td><td>7</td><td>Recovered</td><td>[<xref ref-type="bibr" rid="CR6">6</xref>]</td></tr><tr><td>12</td><td>73 y m</td><td>Germany ex Saudi Arabia</td><td>8 Mar 13</td><td>Yes</td><td>22 Mar 13</td><td>12</td><td>Fatal</td><td>[<xref ref-type="bibr" rid="CR5">5</xref>]</td></tr></tbody></table><table-wrap-foot><p>y – years of age; m - male; nd - no data available.</p></table-wrap-foot></table-wrap><p>To investigate a laboratory surrogate for susceptibility of the kidney to MERS-CoV in comparison to SARS-CoV, we analyzed cryoslides of a healthy human kidney for ACE-2 and DPP-4 expression by immunofluorescence. Staining using polyclonal goat-anti-human ACE-2 immunoglobulin (R&D systems) and polyclonal goat-anti-human DPP-4 immunoglobulin (R&D systems) showed that both receptors are abundantly expressed in the healthy human kidney, and both receptors are predominantly found in the epithelial layer of the renal ducts (Figure <xref rid="Fig2" ref-type="fig">2</xref>A), as well as in human primary epithelial cells derived from these ducts and in epithelial cells from the human airway tract (Figure <xref rid="Fig2" ref-type="fig">2</xref>B).<fig id="Fig2"><label>Figure 2</label><caption><p><bold>SARS- and MERS-CoV receptor expression and virus infection experiments in human primary cells. (A)</bold> SARS- and MERS-CoV receptor expression of human Angiotensin-converting-enzyme-2 (ACE-2) and Dipeptidyl-peptidase-4 (DPP-4), respectively, in cryosections of a healthy human kidney and <bold>(B)</bold> in primary bronchial (HBEpC) and renal (HREpC) epithelial cells. For positive controls, ACE2- and DPP-4-expressing primate cells (kidney cells from African green monkey [Vero E6]) were stained in parallel. Cell lines known to be negative for ACE-2 (kidney cells from Syrian hamster [BHK]) or DPP-4 (kidney cells from African green monkey [COS-7]) were used as negative controls. The white bar represents 50 μm. <bold>(C)</bold> Cell morphology and cytopathic effect (CPE) formation of human primary renal epithelial cells (HREpC) infected with MERS-CoV or SARS-CoV with 0.5 plaque-forming units of either virus per cell. A pronounced CPE formation 20 hours post infection (hpi) was seen only after infection with MERS-CoV in HREpC but not in cells infected with SARS-CoV. No CPE formation was seen in HBEpC infected with MERS-CoV or SARS-CoV (data not shown). Upper row: 100-fold magnification, lower row: 400-fold magnification, bright field microscopy <bold>(D)</bold> Replication of SARS- and MERS-CoV on HBEpC and HREpC determined by real time RT-PCR after 0, 20 and 40 hpi <bold>(E)</bold> Progeny virus measured by titration of supernatants in duplicates in a plaque assay in Vero cells. MERS-CoV replicates in HREpC with peak titers of 6.2 log plaque forming units (PFU)/mL, showing a 2,9-fold log difference between HREpC and HBEpC, while replication of SARS-CoV showed only a 1-fold log difference between bronchial and renal primary cells. Replication levels for each virus used are given as log of the genome equivalents (GEs) <bold>(D)</bold> or as plaque-forming units (PFUs) <bold>(E)</bold>. All virus infection experiments were performed in triplicates. Bars represent mean values, error bars represent standard deviation of triplicates.</p></caption><graphic xlink:href="12985_2013_Article_2343_Fig2_HTML" id="d29e841"></graphic></fig></p><p>To test whether kidney epithelial cells can actually be infected <italic>in-vitro</italic>, we performed comparative infection experiments with MERS- and SARS-CoV, using defined cultures of primary kidney epithelial cells (HREpC, Promocell, Heidelberg). As the bronchoalveolar epithelium of the lung constitutes the primary target compartment for both viruses, infection of human primary bronchial epithelial cells (HBEpC, Promocell, Heidelberg) was studied in parallel. As summarized in Figure <xref rid="Fig2" ref-type="fig">2</xref>, primary cells up to passage 4 were seeded at densities of 4x10<sup>5</sup>/mL and inoculated with either MERS-CoV strain EMC/2012, or SARS-CoV strain Frankfurt-1 at multiplicities of infection (MOI) of 0.5 for 1 hour. Cells were washed twice and supernatants were harvested immediately after washing, as well as 20 and 40 hours later. Cells were checked regularly for appearance of cytopathic effects (CPE) by light microscopy. Replication of both viruses was quantified by titration of supernatants in duplicate plaque assays on Vero cells as described previously, as well as by real-time RT-PCR [<xref ref-type="bibr" rid="CR9">9</xref>, <xref ref-type="bibr" rid="CR16">16</xref>].</p><p>Pronounced CPE consisting of visible and strong cell lysis occurred only in HREpC, and only upon infection with MERS-CoV (Figure <xref rid="Fig2" ref-type="fig">2</xref>C). Neither in HBEpCs upon MERS-CoV infection, nor in HBEpCs or HREpCs upon SARS-CoV infection any CPE was observed. Virus replication was nevertheless detectable by real time RT-PCR in all experiments, confirming successful infection (Figure <xref rid="Fig1" ref-type="fig">1</xref>D). The CPE in HREpCs consisted of rounding and detachment of cells, leading to cell death in the majority of cells already after 20 hours. Comparative quantification of infectious virus production between SARS- and MERS-CoV showed that MERS-CoV replicates to high titers in HREpC with almost 1000-fold higher concentrations of infectious MERS-CoV progeny than in HBEpCs. In SARS-CoV infection, only a small difference between primary kidney and bronchial epithelial cells was seen (Figure <xref rid="Fig1" ref-type="fig">1</xref>E).</p><p>Our results from <italic>in-vitro</italic> infection experiments suggest differences in kidney cell involvement might exist between SARS- and MERS-CoV infection. In a retrospective analysis of 536 SARS cases, only in 36 (6.7%) patients acute renal impairment was diagnosed. ARF occurred rather late in the course of disease after a median of 20 days from the appearance of first symptoms [<xref ref-type="bibr" rid="CR17">17</xref>]. In our literature review of MERS cases, ARF occurred much earlier, namely in 6 of 9 sufficiently-described patients after a median of 11 days. To date, it is difficult to compare these clinical data with experiences from animal models. The only animal that exhibits clinical signs similar to human MERS-CoV infection is the rhesus macaque, but none of the available studies reported kidney failure in macaques [<xref ref-type="bibr" rid="CR18">18</xref>–<xref ref-type="bibr" rid="CR20">20</xref>]. Only very small amounts of viral RNA were detected in kidney tissue, and none in urine. Macaques might be of limited value for the study of MERS-CoV-specific kidney pathology as seen in humans.</p><p>While no autopsy data have become available for patients infected with MERS-CoV, post-mortem studies have been done systematically in SARS victims. Histopathological findings revealed mainly acute tubular necrosis without evidence of glomerular pathology, which is considered to be a consequence of systemic inflammatory response in the context of multi-organ failure, rather than a specific effect of viral infection of the kidney [<xref ref-type="bibr" rid="CR17">17</xref>]. SARS-CoV has never been successfully isolated from <italic>post mortem</italic> kidney tissue of infected patients [<xref ref-type="bibr" rid="CR21">21</xref>]. <italic>In-vitro</italic> studies of SARS-CoV with immortalized human proximal tubular epithelial cells showed replication without cell impairment as seen in our study, while no infection of podocyte cell lines and only low-level replication in glomerular mesangial cells (MC) was seen, providing further evidence against specific involvement of the renal tract in SARS-CoV infection [<xref ref-type="bibr" rid="CR22">22</xref>]. In contrast, MERS-CoV was shown to efficiently replicate in a broad range of bat, primate and also human kidney epithelial cell lines that are commonly used as laboratory models [<xref ref-type="bibr" rid="CR9">9</xref>]. The abundant expression of both viruses’ entry receptors in kidney epithelium argues against receptor-dependent limitations to viral kidney tropism. Specific interference of MERS-CoV with the induction of the interferon response provides one of many possible explanations for an increased capacity of MERS-CoV to replicate in kidney cells [<xref ref-type="bibr" rid="CR23">23</xref>]. The clear differences in viral permissiveness of primary kidney epithelial cells suggest these cells to be appropriate models for the identification of host-specific restriction factors in the future. We are aware that cell culture resembles a limited model of viral infection which will not reflect the complexity of infection <italic>in-vivo</italic>. Nevertheless, our results have some congruence with clinical observations in a well-investigated MERS case [<xref ref-type="bibr" rid="CR5">5</xref>]. Virus in the urine has been detected as late as day 12 of illness, albeit at low concentrations. Virus was detected in the urine but not in the blood, which could indicate autonomous virus replication in the kidneys. Of note, by using a model to assess the ability of CoVs to persist in the environment, it was shown that MERS-CoV has similarities to viruses that are transmitted via the fecal-oral route [<xref ref-type="bibr" rid="CR24">24</xref>]. The authors suggest that this could hint for oral-urine transmission of MERS-CoV. Further data on virus shedding in the urine over the course of disease are urgently needed. If the kidney should indeed constitute a site of primary virus replication, shedding of virus in the urine might provide a possible source for human-to-human transmission, especially in health-care settings or among close family contacts [<xref ref-type="bibr" rid="CR3">3</xref>, <xref ref-type="bibr" rid="CR6">6</xref>, <xref ref-type="bibr" rid="CR7">7</xref>]. Clinical guidelines should consider the possibility that MERS patients may benefit from early induction of renoprotective treatment.</p></body><back><app-group><app id="App1"><sec id="Sec1"><title>Authors’ original submitted files for images</title><p>Below are the links to the authors’ original submitted files for images.<media position="anchor" xlink:href="12985_2013_2343_MOESM1_ESM.tiff" id="MOESM1"><caption><p>Authors’ original file for figure 1</p></caption></media><media position="anchor" xlink:href="12985_2013_2343_MOESM2_ESM.tiff" id="MOESM2"><caption><p>Authors’ original file for figure 2</p></caption></media></p></sec></app></app-group><fn-group><fn><p><bold>Competing interests</bold></p><p>The authors declare that they have no competing interests.</p></fn><fn><p><bold>Authors’ contributions</bold></p><p>IE, MAM designed the experiments, IE, MAM, SK performed experiments and analysis, IE, CD wrote the manuscript, IE, DNG, CD contributed to the final version of the manuscript. All authors read and approved the final manuscript.</p></fn></fn-group><ack><title>Acknowledgements</title><p>This work was funded by FP7 European research project ANTIGONE (contract number 278976), as well as an infrastructural grant from the German Centre for Infection Research (DZIF). We thank the National Center for Tumor Diseases (NCT), Heidelberg, for tissue sections. We thank Bart Haagmans, Department of Virology, Erasmus Medical Center, Rotterdam, for COS-7 cells.</p></ack><ref-list id="Bib1"><title>References</title><ref id="CR1"><label>1.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Peiris</surname><given-names>JS</given-names></name><name><surname>Guan</surname><given-names>Y</given-names></name><name><surname>Yuen</surname><given-names>KY</given-names></name></person-group><article-title>Severe acute respiratory syndrome</article-title><source>Nat Med</source><year>2004</year><volume>10</volume><fpage>S88</fpage><lpage>S97</lpage><pub-id pub-id-type="doi">10.1038/nm1143</pub-id><pub-id pub-id-type="pmid">15577937</pub-id></element-citation></ref><ref id="CR2"><label>2.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zaki</surname><given-names>AM</given-names></name><name><surname>van Boheemen</surname><given-names>S</given-names></name><name><surname>Bestebroer</surname><given-names>TM</given-names></name><name><surname>Osterhaus</surname><given-names>AD</given-names></name><name><surname>Fouchier</surname><given-names>RA</given-names></name></person-group><article-title>Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia</article-title><source>N Engl J Med</source><year>2012</year><volume>367</volume><fpage>1814</fpage><lpage>1820</lpage><pub-id pub-id-type="doi">10.1056/NEJMoa1211721</pub-id><pub-id pub-id-type="pmid">23075143</pub-id></element-citation></ref><ref id="CR3"><label>3.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Memish</surname><given-names>ZA</given-names></name><name><surname>Zumla</surname><given-names>AI</given-names></name><name><surname>Al-Hakeem</surname><given-names>RF</given-names></name><name><surname>Al-Rabeeah</surname><given-names>AA</given-names></name><name><surname>Stephens</surname><given-names>GM</given-names></name></person-group><article-title>Family cluster of Middle East respiratory syndrome coronavirus infections</article-title><source>N Engl J Med</source><year>2013</year><volume>368</volume><fpage>2487</fpage><lpage>2494</lpage><pub-id pub-id-type="doi">10.1056/NEJMoa1303729</pub-id><pub-id pub-id-type="pmid">23718156</pub-id></element-citation></ref><ref id="CR4"><label>4.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Assiri</surname><given-names>A</given-names></name><name><surname>McGeer</surname><given-names>A</given-names></name><name><surname>Perl</surname><given-names>TM</given-names></name><name><surname>Price</surname><given-names>CS</given-names></name><name><surname>Al Rabeeah</surname><given-names>AA</given-names></name><name><surname>Cummings</surname><given-names>DA</given-names></name><name><surname>Alabdullatif</surname><given-names>ZN</given-names></name><name><surname>Assad</surname><given-names>M</given-names></name><name><surname>Almulhim</surname><given-names>A</given-names></name><name><surname>Makhdoom</surname><given-names>H</given-names></name><etal></etal></person-group><article-title>Hospital outbreak of Middle East respiratory syndrome coronavirus</article-title><source>N Engl J Med</source><year>2013</year><volume>369</volume><fpage>407</fpage><lpage>416</lpage><pub-id pub-id-type="doi">10.1056/NEJMoa1306742</pub-id><pub-id pub-id-type="pmid">23782161</pub-id></element-citation></ref><ref id="CR5"><label>5.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Drosten</surname><given-names>C</given-names></name><name><surname>Seilmaier</surname><given-names>M</given-names></name><name><surname>Corman</surname><given-names>VM</given-names></name><name><surname>Hartmann</surname><given-names>W</given-names></name><name><surname>Scheible</surname><given-names>G</given-names></name><name><surname>Sack</surname><given-names>S</given-names></name><name><surname>Guggemos</surname><given-names>W</given-names></name><name><surname>Kallies</surname><given-names>R</given-names></name><name><surname>Muth</surname><given-names>D</given-names></name><name><surname>Junglen</surname><given-names>S</given-names></name><etal></etal></person-group><article-title>Clinical features and virological analysis of a case of Middle East respiratory syndrome coronavirus infection</article-title><source>Lancet Infect Dis</source><year>2013</year><volume>13</volume><fpage>745</fpage><lpage>751</lpage><pub-id pub-id-type="doi">10.1016/S1473-3099(13)70154-3</pub-id><pub-id pub-id-type="pmid">23782859</pub-id></element-citation></ref><ref id="CR6"><label>6.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Guery</surname><given-names>B</given-names></name><name><surname>Poissy</surname><given-names>J</given-names></name><name><surname>el Mansouf</surname><given-names>L</given-names></name><name><surname>Sejourne</surname><given-names>C</given-names></name><name><surname>Ettahar</surname><given-names>N</given-names></name><name><surname>Lemaire</surname><given-names>X</given-names></name><name><surname>Vuotto</surname><given-names>F</given-names></name><name><surname>Goffard</surname><given-names>A</given-names></name><name><surname>Behillil</surname><given-names>S</given-names></name><name><surname>Enouf</surname><given-names>V</given-names></name><etal></etal></person-group><article-title>Clinical features and viral diagnosis of two cases of infection with Middle East respiratory syndrome coronavirus: a report of nosocomial transmission</article-title><source>Lancet</source><year>2013</year><volume>381</volume><fpage>2265</fpage><lpage>2272</lpage><pub-id pub-id-type="doi">10.1016/S0140-6736(13)60982-4</pub-id><pub-id pub-id-type="pmid">23727167</pub-id></element-citation></ref><ref id="CR7"><label>7.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pollack</surname><given-names>MP</given-names></name><name><surname>Pringle</surname><given-names>C</given-names></name><name><surname>Madoff</surname><given-names>LC</given-names></name><name><surname>Memish</surname><given-names>ZA</given-names></name></person-group><article-title>Latest outbreak news from ProMED-mail: novel coronavirus – Middle East</article-title><source>Int J Infect Dis</source><year>2013</year><volume>17</volume><fpage>e143</fpage><lpage>e144</lpage><pub-id pub-id-type="doi">10.1016/j.ijid.2012.12.001</pub-id><pub-id pub-id-type="pmid">23270612</pub-id></element-citation></ref><ref id="CR8"><label>8.</label><element-citation publication-type="book"><person-group person-group-type="author"><collab>The WHO MERS-CoV Research Group</collab></person-group><article-title>State of knowledge and data gaps of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Humans</article-title><source>PLOS Currents Outbreaks</source><year>2013</year></element-citation></ref><ref id="CR9"><label>9.</label><element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Muller</surname><given-names>MA</given-names></name><name><surname>Raj</surname><given-names>VS</given-names></name><name><surname>Muth</surname><given-names>D</given-names></name><name><surname>Meyer</surname><given-names>B</given-names></name><name><surname>Kallies</surname><given-names>S</given-names></name><name><surname>Smits</surname><given-names>SL</given-names></name><name><surname>Wollny</surname><given-names>R</given-names></name><name><surname>Bestebroer</surname><given-names>TM</given-names></name><name><surname>Specht</surname><given-names>S</given-names></name><name><surname>Suliman</surname><given-names>T</given-names></name><etal></etal></person-group><article-title>Human coronavirus EMC does not require the SARS-coronavirus receptor and maintains broad replicative capability in mammalian cell lines</article-title><source>M Bio</source><year>2012</year></element-citation></ref><ref id="CR10"><label>10.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Raj</surname><given-names>VS</given-names></name><name><surname>Mou</surname><given-names>H</given-names></name><name><surname>Smits</surname><given-names>SL</given-names></name><name><surname>Dekkers</surname><given-names>DH</given-names></name><name><surname>Muller</surname><given-names>MA</given-names></name><name><surname>Dijkman</surname><given-names>R</given-names></name><name><surname>Muth</surname><given-names>D</given-names></name><name><surname>Demmers</surname><given-names>JA</given-names></name><name><surname>Zaki</surname><given-names>A</given-names></name><name><surname>Fouchier</surname><given-names>RA</given-names></name><etal></etal></person-group><article-title>Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC</article-title><source>Nature</source><year>2013</year><volume>495</volume><fpage>251</fpage><lpage>254</lpage><pub-id pub-id-type="doi">10.1038/nature12005</pub-id><pub-id pub-id-type="pmid">23486063</pub-id></element-citation></ref><ref id="CR11"><label>11.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hamming</surname><given-names>I</given-names></name><name><surname>Cooper</surname><given-names>ME</given-names></name><name><surname>Haagmans</surname><given-names>BL</given-names></name><name><surname>Hooper</surname><given-names>NM</given-names></name><name><surname>Korstanje</surname><given-names>R</given-names></name><name><surname>Osterhaus</surname><given-names>AD</given-names></name><name><surname>Timens</surname><given-names>W</given-names></name><name><surname>Turner</surname><given-names>AJ</given-names></name><name><surname>Navis</surname><given-names>G</given-names></name><name><surname>van Goor</surname><given-names>H</given-names></name></person-group><article-title>The emerging role of ACE2 in physiology and disease</article-title><source>J Pathol</source><year>2007</year><volume>212</volume><fpage>1</fpage><lpage>11</lpage><pub-id pub-id-type="doi">10.1002/path.2162</pub-id><pub-id pub-id-type="pmid">17464936</pub-id></element-citation></ref><ref id="CR12"><label>12.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lambeir</surname><given-names>AM</given-names></name><name><surname>Durinx</surname><given-names>C</given-names></name><name><surname>Scharpe</surname><given-names>S</given-names></name><name><surname>De Meester</surname><given-names>I</given-names></name></person-group><article-title>Dipeptidyl-peptidase IV from bench to bedside: an update on structural properties, functions, and clinical aspects of the enzyme DPP IV</article-title><source>Crit Rev Clin Lab Sci</source><year>2003</year><volume>40</volume><fpage>209</fpage><lpage>294</lpage><pub-id pub-id-type="doi">10.1080/713609354</pub-id><pub-id pub-id-type="pmid">12892317</pub-id></element-citation></ref><ref id="CR13"><label>13.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>de Groot</surname><given-names>RJ</given-names></name><name><surname>Baker</surname><given-names>SC</given-names></name><name><surname>Baric</surname><given-names>RS</given-names></name><name><surname>Brown</surname><given-names>CS</given-names></name><name><surname>Drosten</surname><given-names>C</given-names></name><name><surname>Enjuanes</surname><given-names>L</given-names></name><name><surname>Fouchier</surname><given-names>RA</given-names></name><name><surname>Galiano</surname><given-names>M</given-names></name><name><surname>Gorbalenya</surname><given-names>AE</given-names></name><name><surname>Memish</surname><given-names>ZA</given-names></name><etal></etal></person-group><article-title>Middle East respiratory syndrome coronavirus (MERS-CoV): announcement of the Coronavirus Study Group</article-title><source>J Virol</source><year>2013</year><volume>87</volume><fpage>7790</fpage><lpage>7792</lpage><pub-id pub-id-type="doi">10.1128/JVI.01244-13</pub-id><pub-id pub-id-type="pmid">23678167</pub-id></element-citation></ref><ref id="CR14"><label>14.</label><element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Buchholz</surname><given-names>U</given-names></name><name><surname>Muller</surname><given-names>MA</given-names></name><name><surname>Nitsche</surname><given-names>A</given-names></name><name><surname>Sanewski</surname><given-names>A</given-names></name><name><surname>Wevering</surname><given-names>N</given-names></name><name><surname>Bauer-Balci</surname><given-names>T</given-names></name><name><surname>Bonin</surname><given-names>F</given-names></name><name><surname>Drosten</surname><given-names>C</given-names></name><name><surname>Schweiger</surname><given-names>B</given-names></name><name><surname>Wolff</surname><given-names>T</given-names></name><etal></etal></person-group><article-title>Contact investigation of a case of human novel coronavirus infection treated in a German hospital, October-November 2012</article-title><source>Euro Surveill</source><year>2013</year></element-citation></ref><ref id="CR15"><label>15.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bermingham</surname><given-names>A</given-names></name><name><surname>Chand</surname><given-names>MA</given-names></name><name><surname>Brown</surname><given-names>CS</given-names></name><name><surname>Aarons</surname><given-names>E</given-names></name><name><surname>Tong</surname><given-names>C</given-names></name><name><surname>Langrish</surname><given-names>C</given-names></name><name><surname>Hoschler</surname><given-names>K</given-names></name><name><surname>Brown</surname><given-names>K</given-names></name><name><surname>Galiano</surname><given-names>M</given-names></name><name><surname>Myers</surname><given-names>R</given-names></name><etal></etal></person-group><article-title>Severe respiratory illness caused by a novel coronavirus, in a patient transferred to the United Kingdom from the Middle East, September 2012</article-title><source>Euro Surveill</source><year>2012</year><volume>17</volume><fpage>20290</fpage><pub-id pub-id-type="pmid">23078800</pub-id></element-citation></ref><ref id="CR16"><label>16.</label><element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Corman</surname><given-names>VM</given-names></name><name><surname>Eckerle</surname><given-names>I</given-names></name><name><surname>Bleicker</surname><given-names>T</given-names></name><name><surname>Zaki</surname><given-names>A</given-names></name><name><surname>Landt</surname><given-names>O</given-names></name><name><surname>Eschbach-Bludau</surname><given-names>M</given-names></name><name><surname>van Boheemen</surname><given-names>S</given-names></name><name><surname>Gopal</surname><given-names>R</given-names></name><name><surname>Ballhause</surname><given-names>M</given-names></name><name><surname>Bestebroer</surname><given-names>TM</given-names></name><etal></etal></person-group><article-title>Detection of a novel human coronavirus by real-time reverse-transcription polymerase chain reaction</article-title><source>Euro Surveill</source><year>2012</year></element-citation></ref><ref id="CR17"><label>17.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chu</surname><given-names>KH</given-names></name><name><surname>Tsang</surname><given-names>WK</given-names></name><name><surname>Tang</surname><given-names>CS</given-names></name><name><surname>Lam</surname><given-names>MF</given-names></name><name><surname>Lai</surname><given-names>FM</given-names></name><name><surname>To</surname><given-names>KF</given-names></name><name><surname>Fung</surname><given-names>KS</given-names></name><name><surname>Tang</surname><given-names>HL</given-names></name><name><surname>Yan</surname><given-names>WW</given-names></name><name><surname>Chan</surname><given-names>HW</given-names></name><etal></etal></person-group><article-title>Acute renal impairment in coronavirus-associated severe acute respiratory syndrome</article-title><source>Kidney Int</source><year>2005</year><volume>67</volume><fpage>698</fpage><lpage>705</lpage><pub-id pub-id-type="doi">10.1111/j.1523-1755.2005.67130.x</pub-id><pub-id pub-id-type="pmid">15673319</pub-id></element-citation></ref><ref id="CR18"><label>18.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Falzarano</surname><given-names>D</given-names></name><name><surname>de Wit</surname><given-names>E</given-names></name><name><surname>Rasmussen</surname><given-names>AL</given-names></name><name><surname>Feldmann</surname><given-names>F</given-names></name><name><surname>Okumura</surname><given-names>A</given-names></name><name><surname>Scott</surname><given-names>DP</given-names></name><name><surname>Brining</surname><given-names>D</given-names></name><name><surname>Bushmaker</surname><given-names>T</given-names></name><name><surname>Martellaro</surname><given-names>C</given-names></name><name><surname>Baseler</surname><given-names>L</given-names></name><etal></etal></person-group><article-title>Treatment with interferon-alpha2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques</article-title><source>Nat Med</source><year>2013</year><volume>19</volume><fpage>1313</fpage><lpage>1317</lpage><pub-id pub-id-type="doi">10.1038/nm.3362</pub-id><pub-id pub-id-type="pmid">24013700</pub-id></element-citation></ref><ref id="CR19"><label>19.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Munster</surname><given-names>VJ</given-names></name><name><surname>de Wit</surname><given-names>E</given-names></name><name><surname>Feldmann</surname><given-names>H</given-names></name></person-group><article-title>Pneumonia from human coronavirus in a macaque model</article-title><source>N Engl J Med</source><year>2013</year><volume>368</volume><fpage>1560</fpage><lpage>1562</lpage><pub-id pub-id-type="doi">10.1056/NEJMc1215691</pub-id><pub-id pub-id-type="pmid">23550601</pub-id></element-citation></ref><ref id="CR20"><label>20.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>de Wit</surname><given-names>E</given-names></name><name><surname>Rasmussen</surname><given-names>AL</given-names></name><name><surname>Falzarano</surname><given-names>D</given-names></name><name><surname>Bushmaker</surname><given-names>T</given-names></name><name><surname>Feldmann</surname><given-names>F</given-names></name><name><surname>Brining</surname><given-names>DL</given-names></name><name><surname>Fischer</surname><given-names>ER</given-names></name><name><surname>Martellaro</surname><given-names>C</given-names></name><name><surname>Okumura</surname><given-names>A</given-names></name><name><surname>Chang</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>Middle East respiratory syndrome coronavirus (MERS-CoV) causes transient lower respiratory tract infection in rhesus macaques</article-title><source>Proc Natl Acad Sci</source><year>2013</year><volume>110</volume><fpage>16598</fpage><lpage>16603</lpage><pub-id pub-id-type="doi">10.1073/pnas.1310744110</pub-id><pub-id pub-id-type="pmid">24062443</pub-id></element-citation></ref><ref id="CR21"><label>21.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tang</surname><given-names>JW</given-names></name><name><surname>To</surname><given-names>KF</given-names></name><name><surname>Lo</surname><given-names>AW</given-names></name><name><surname>Sung</surname><given-names>JJ</given-names></name><name><surname>Ng</surname><given-names>HK</given-names></name><name><surname>Chan</surname><given-names>PK</given-names></name></person-group><article-title>Quantitative temporal-spatial distribution of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) in post-mortem tissues</article-title><source>J Med Virol</source><year>2007</year><volume>79</volume><fpage>1245</fpage><lpage>1253</lpage><pub-id pub-id-type="doi">10.1002/jmv.20873</pub-id><pub-id pub-id-type="pmid">17607787</pub-id></element-citation></ref><ref id="CR22"><label>22.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pacciarini</surname><given-names>F</given-names></name><name><surname>Ghezzi</surname><given-names>S</given-names></name><name><surname>Canducci</surname><given-names>F</given-names></name><name><surname>Sims</surname><given-names>A</given-names></name><name><surname>Sampaolo</surname><given-names>M</given-names></name><name><surname>Ferioli</surname><given-names>E</given-names></name><name><surname>Clementi</surname><given-names>M</given-names></name><name><surname>Poli</surname><given-names>G</given-names></name><name><surname>Conaldi</surname><given-names>PG</given-names></name><name><surname>Baric</surname><given-names>R</given-names></name><name><surname>Vicenzi</surname><given-names>E</given-names></name></person-group><article-title>Persistent replication of severe acute respiratory syndrome coronavirus in human tubular kidney cells selects for adaptive mutations in the membrane protein</article-title><source>J Virol</source><year>2008</year><volume>82</volume><fpage>5137</fpage><lpage>5144</lpage><pub-id pub-id-type="doi">10.1128/JVI.00096-08</pub-id><pub-id pub-id-type="pmid">18367528</pub-id></element-citation></ref><ref id="CR23"><label>23.</label><element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Niemeyer</surname><given-names>D</given-names></name><name><surname>Zillinger</surname><given-names>T</given-names></name><name><surname>Muth</surname><given-names>D</given-names></name><name><surname>Zielecki</surname><given-names>F</given-names></name><name><surname>Horvath</surname><given-names>G</given-names></name><name><surname>Suliman</surname><given-names>T</given-names></name><name><surname>Barchet</surname><given-names>W</given-names></name><name><surname>Weber</surname><given-names>F</given-names></name><name><surname>Drosten</surname><given-names>C</given-names></name><name><surname>Muller</surname><given-names>MA</given-names></name></person-group><article-title>Middle East respiratory syndrome coronavirus accessory protein 4a is a type I interferon antagonist</article-title><source>J Virol</source><year>2013</year></element-citation></ref><ref id="CR24"><label>24.</label><element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Goh</surname><given-names>GK</given-names></name><name><surname>Dunker</surname><given-names>AK</given-names></name><name><surname>Uversky</surname><given-names>V</given-names></name></person-group><article-title>Prediction of intrinsic disorder in MERS-CoV/HCoV-EMC supports a high oral-fecal transmission</article-title><source>PLOS Currents Outbreaks</source><year>2013</year></element-citation></ref></ref-list></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/MersV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000173 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 000173 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= MersV1
|flux= Pmc
|étape= Corpus
|type= RBID
|clé= PMC:3878046
|texte= In-vitro renal epithelial cell infection reveals a viral kidney tropism as a potential mechanism for acute renal failure during Middle East Respiratory Syndrome (MERS) Coronavirus infection
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/RBID.i -Sk "pubmed:24364985" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd \
| NlmPubMed2Wicri -a MersV1
| This area was generated with Dilib version V0.6.33. |  |