Inhibition of Proprotein Convertases Abrogates Processing of the Middle Eastern Respiratory Syndrome Coronavirus Spike Protein in Infected Cells but Does Not Reduce Viral Infectivity
Identifieur interne : 000E22 ( Pmc/Curation ); précédent : 000E21; suivant : 000E23Inhibition of Proprotein Convertases Abrogates Processing of the Middle Eastern Respiratory Syndrome Coronavirus Spike Protein in Infected Cells but Does Not Reduce Viral Infectivity
Auteurs : Stefanie Gierer ; Marcel A. Müller ; Adeline Heurich ; Daniel Ritz ; Benjamin L. Springstein ; Christina B. Karsten [Allemagne] ; Alexander Schendzielorz ; Kerstin Gnir ; Christian Drosten ; Stefan PöhlmannSource :
- The Journal of Infectious Diseases [ 0022-1899 ] ; 2014.
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) infection is associated with a high case-fatality rate, and the potential pandemic spread of the virus is a public health concern. The spike protein of MERS-CoV (MERS-S) facilitates viral entry into host cells, which depends on activation of MERS-S by cellular proteases. Proteolytic activation of MERS-S during viral uptake into target cells has been demonstrated. However, it is unclear whether MERS-S is also cleaved during S protein synthesis in infected cells and whether cleavage is required for MERS-CoV infectivity. Here, we show that MERS-S is processed by proprotein convertases in MERS-S–transfected and MERS-CoV–infected cells and that several RXXR motifs located at the border between the surface and transmembrane subunit of MERS-S are required for efficient proteolysis. However, blockade of proprotein convertases did not impact MERS-S–dependent transduction of target cells expressing high amounts of the viral receptor, DPP4, and did not modulate MERS-CoV infectivity. These results show that MERS-S is a substrate for proprotein convertases and demonstrate that processing by these enzymes is dispensable for S protein activation. Efforts to inhibit MERS-CoV infection by targeting host cell proteases should therefore focus on enzymes that process MERS-S during viral uptake into target cells.
Url:
DOI: 10.1093/infdis/jiu407
PubMed: 25057042
PubMed Central: 7107327
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: Pour aller vers cette notice dans l'étape Curation :000E22
Links to Exploration step
PMC:7107327Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Inhibition of Proprotein Convertases Abrogates Processing of the Middle Eastern Respiratory Syndrome Coronavirus Spike Protein in Infected Cells but Does Not Reduce Viral Infectivity</title><author><name sortKey="Gierer, Stefanie" sort="Gierer, Stefanie" uniqKey="Gierer S" first="Stefanie" last="Gierer">Stefanie Gierer</name><affiliation><nlm:aff id="af1"><addr-line>Infection Biology Unit</addr-line>,<institution>German Primate Center</institution>,<addr-line>Göttingen</addr-line></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="af2"><addr-line>Institute of Virology</addr-line>,<institution>University of Bonn Medical Center</institution></nlm:aff></affiliation></author><author><name sortKey="Heurich, Adeline" sort="Heurich, Adeline" uniqKey="Heurich A" first="Adeline" last="Heurich">Adeline Heurich</name><affiliation><nlm:aff id="af1"><addr-line>Infection Biology Unit</addr-line>,<institution>German Primate Center</institution>,<addr-line>Göttingen</addr-line></nlm:aff></affiliation></author><author><name sortKey="Ritz, Daniel" sort="Ritz, Daniel" uniqKey="Ritz D" first="Daniel" last="Ritz">Daniel Ritz</name><affiliation><nlm:aff id="af2"><addr-line>Institute of Virology</addr-line>,<institution>University of Bonn Medical Center</institution></nlm:aff></affiliation></author><author><name sortKey="Springstein, Benjamin L" sort="Springstein, Benjamin L" uniqKey="Springstein B" first="Benjamin L." last="Springstein">Benjamin L. Springstein</name><affiliation><nlm:aff id="af1"><addr-line>Infection Biology Unit</addr-line>,<institution>German Primate Center</institution>,<addr-line>Göttingen</addr-line></nlm:aff></affiliation></author><author><name sortKey="Karsten, Christina B" sort="Karsten, Christina B" uniqKey="Karsten C" first="Christina B." last="Karsten">Christina B. Karsten</name><affiliation><nlm:aff id="af1"><addr-line>Infection Biology Unit</addr-line>,<institution>German Primate Center</institution>,<addr-line>Göttingen</addr-line></nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af3"><addr-line>Institute for Cellular Chemistry</addr-line>,<institution>Hannover Medical School</institution>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Schendzielorz, Alexander" sort="Schendzielorz, Alexander" uniqKey="Schendzielorz A" first="Alexander" last="Schendzielorz">Alexander Schendzielorz</name><affiliation><nlm:aff id="af1"><addr-line>Infection Biology Unit</addr-line>,<institution>German Primate Center</institution>,<addr-line>Göttingen</addr-line></nlm:aff></affiliation></author><author><name sortKey="Gnir, Kerstin" sort="Gnir, Kerstin" uniqKey="Gnir K" first="Kerstin" last="Gnir">Kerstin Gnir</name><affiliation><nlm:aff id="af1"><addr-line>Infection Biology Unit</addr-line>,<institution>German Primate Center</institution>,<addr-line>Göttingen</addr-line></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="af2"><addr-line>Institute of Virology</addr-line>,<institution>University of Bonn Medical Center</institution></nlm:aff></affiliation></author><author><name sortKey="Pohlmann, Stefan" sort="Pohlmann, Stefan" uniqKey="Pohlmann S" first="Stefan" last="Pöhlmann">Stefan Pöhlmann</name><affiliation><nlm:aff id="af1"><addr-line>Infection Biology Unit</addr-line>,<institution>German Primate Center</institution>,<addr-line>Göttingen</addr-line></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25057042</idno><idno type="pmc">7107327</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7107327</idno><idno type="RBID">PMC:7107327</idno><idno type="doi">10.1093/infdis/jiu407</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000E22</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000E22</idno><idno type="wicri:Area/Pmc/Curation">000E22</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000E22</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Inhibition of Proprotein Convertases Abrogates Processing of the Middle Eastern Respiratory Syndrome Coronavirus Spike Protein in Infected Cells but Does Not Reduce Viral Infectivity</title><author><name sortKey="Gierer, Stefanie" sort="Gierer, Stefanie" uniqKey="Gierer S" first="Stefanie" last="Gierer">Stefanie Gierer</name><affiliation><nlm:aff id="af1"><addr-line>Infection Biology Unit</addr-line>,<institution>German Primate Center</institution>,<addr-line>Göttingen</addr-line></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="af2"><addr-line>Institute of Virology</addr-line>,<institution>University of Bonn Medical Center</institution></nlm:aff></affiliation></author><author><name sortKey="Heurich, Adeline" sort="Heurich, Adeline" uniqKey="Heurich A" first="Adeline" last="Heurich">Adeline Heurich</name><affiliation><nlm:aff id="af1"><addr-line>Infection Biology Unit</addr-line>,<institution>German Primate Center</institution>,<addr-line>Göttingen</addr-line></nlm:aff></affiliation></author><author><name sortKey="Ritz, Daniel" sort="Ritz, Daniel" uniqKey="Ritz D" first="Daniel" last="Ritz">Daniel Ritz</name><affiliation><nlm:aff id="af2"><addr-line>Institute of Virology</addr-line>,<institution>University of Bonn Medical Center</institution></nlm:aff></affiliation></author><author><name sortKey="Springstein, Benjamin L" sort="Springstein, Benjamin L" uniqKey="Springstein B" first="Benjamin L." last="Springstein">Benjamin L. Springstein</name><affiliation><nlm:aff id="af1"><addr-line>Infection Biology Unit</addr-line>,<institution>German Primate Center</institution>,<addr-line>Göttingen</addr-line></nlm:aff></affiliation></author><author><name sortKey="Karsten, Christina B" sort="Karsten, Christina B" uniqKey="Karsten C" first="Christina B." last="Karsten">Christina B. Karsten</name><affiliation><nlm:aff id="af1"><addr-line>Infection Biology Unit</addr-line>,<institution>German Primate Center</institution>,<addr-line>Göttingen</addr-line></nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af3"><addr-line>Institute for Cellular Chemistry</addr-line>,<institution>Hannover Medical School</institution>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Schendzielorz, Alexander" sort="Schendzielorz, Alexander" uniqKey="Schendzielorz A" first="Alexander" last="Schendzielorz">Alexander Schendzielorz</name><affiliation><nlm:aff id="af1"><addr-line>Infection Biology Unit</addr-line>,<institution>German Primate Center</institution>,<addr-line>Göttingen</addr-line></nlm:aff></affiliation></author><author><name sortKey="Gnir, Kerstin" sort="Gnir, Kerstin" uniqKey="Gnir K" first="Kerstin" last="Gnir">Kerstin Gnir</name><affiliation><nlm:aff id="af1"><addr-line>Infection Biology Unit</addr-line>,<institution>German Primate Center</institution>,<addr-line>Göttingen</addr-line></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="af2"><addr-line>Institute of Virology</addr-line>,<institution>University of Bonn Medical Center</institution></nlm:aff></affiliation></author><author><name sortKey="Pohlmann, Stefan" sort="Pohlmann, Stefan" uniqKey="Pohlmann S" first="Stefan" last="Pöhlmann">Stefan Pöhlmann</name><affiliation><nlm:aff id="af1"><addr-line>Infection Biology Unit</addr-line>,<institution>German Primate Center</institution>,<addr-line>Göttingen</addr-line></nlm:aff></affiliation></author></analytic><series><title level="j">The Journal of Infectious Diseases</title><idno type="ISSN">0022-1899</idno><idno type="eISSN">1537-6613</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Abstract</title><p>Middle East respiratory syndrome coronavirus (MERS-CoV) infection is associated with a high case-fatality rate, and the potential pandemic spread of the virus is a public health concern. The spike protein of MERS-CoV (MERS-S) facilitates viral entry into host cells, which depends on activation of MERS-S by cellular proteases. Proteolytic activation of MERS-S during viral uptake into target cells has been demonstrated. However, it is unclear whether MERS-S is also cleaved during S protein synthesis in infected cells and whether cleavage is required for MERS-CoV infectivity. Here, we show that MERS-S is processed by proprotein convertases in MERS-S–transfected and MERS-CoV–infected cells and that several RXXR motifs located at the border between the surface and transmembrane subunit of MERS-S are required for efficient proteolysis. However, blockade of proprotein convertases did not impact MERS-S–dependent transduction of target cells expressing high amounts of the viral receptor, DPP4, and did not modulate MERS-CoV infectivity. These results show that MERS-S is a substrate for proprotein convertases and demonstrate that processing by these enzymes is dispensable for S protein activation. Efforts to inhibit MERS-CoV infection by targeting host cell proteases should therefore focus on enzymes that process MERS-S during viral uptake into target cells.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Graham, Rl" uniqKey="Graham R">RL Graham</name></author><author><name sortKey="Donaldson, Ef" uniqKey="Donaldson E">EF Donaldson</name></author><author><name sortKey="Baric, Rs" uniqKey="Baric R">RS Baric</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hilgenfeld, R" uniqKey="Hilgenfeld R">R Hilgenfeld</name></author><author><name sortKey="Peiris, M" uniqKey="Peiris M">M Peiris</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Drexler, Jf" uniqKey="Drexler J">JF Drexler</name></author><author><name sortKey="Corman, Vm" uniqKey="Corman V">VM Corman</name></author><author><name sortKey="Drosten, C" uniqKey="Drosten C">C Drosten</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ge, Xy" uniqKey="Ge X">XY Ge</name></author><author><name sortKey="Li, Jl" uniqKey="Li J">JL Li</name></author><author><name sortKey="Yang, Xl" uniqKey="Yang X">XL Yang</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="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></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></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mailles, A" uniqKey="Mailles A">A Mailles</name></author><author><name sortKey="Blanckaert, K" uniqKey="Blanckaert K">K Blanckaert</name></author><author><name sortKey="Chaud, P" uniqKey="Chaud P">P Chaud</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Belouzard, S" uniqKey="Belouzard S">S Belouzard</name></author><author><name sortKey="Millet, Jk" uniqKey="Millet J">JK Millet</name></author><author><name sortKey="Licitra, Bn" uniqKey="Licitra B">BN Licitra</name></author><author><name sortKey="Whittaker, Gr" uniqKey="Whittaker G">GR Whittaker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Heald Sargent, T" uniqKey="Heald Sargent T">T Heald-Sargent</name></author><author><name sortKey="Gallagher, T" uniqKey="Gallagher T">T Gallagher</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></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gierer, S" uniqKey="Gierer S">S Gierer</name></author><author><name sortKey="Bertram, S" uniqKey="Bertram S">S Bertram</name></author><author><name sortKey="Kaup, F" uniqKey="Kaup F">F Kaup</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Simmons, G" uniqKey="Simmons G">G Simmons</name></author><author><name sortKey="Zmora, P" uniqKey="Zmora P">P Zmora</name></author><author><name sortKey="Gierer, S" uniqKey="Gierer S">S Gierer</name></author><author><name sortKey="Heurich, A" uniqKey="Heurich A">A Heurich</name></author><author><name sortKey="Pohlmann, S" uniqKey="Pohlmann S">S Pöhlmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shirato, K" uniqKey="Shirato K">K Shirato</name></author><author><name sortKey="Kawase, M" uniqKey="Kawase M">M Kawase</name></author><author><name sortKey="Matsuyama, S" uniqKey="Matsuyama S">S Matsuyama</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Qian, Z" uniqKey="Qian Z">Z Qian</name></author><author><name sortKey="Dominguez, Sr" uniqKey="Dominguez S">SR Dominguez</name></author><author><name sortKey="Holmes, Kv" uniqKey="Holmes K">KV Holmes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yamada, Y" uniqKey="Yamada Y">Y Yamada</name></author><author><name sortKey="Liu, Dx" uniqKey="Liu D">DX Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hallenberger, S" uniqKey="Hallenberger S">S Hallenberger</name></author><author><name sortKey="Bosch, V" uniqKey="Bosch V">V Bosch</name></author><author><name sortKey="Angliker, H" uniqKey="Angliker H">H Angliker</name></author><author><name sortKey="Shaw, E" uniqKey="Shaw E">E Shaw</name></author><author><name sortKey="Klenk, Hd" uniqKey="Klenk H">HD Klenk</name></author><author><name sortKey="Garten, W" uniqKey="Garten W">W Garten</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stieneke Grober, A" uniqKey="Stieneke Grober A">A Stieneke-Grober</name></author><author><name sortKey="Vey, M" uniqKey="Vey M">M Vey</name></author><author><name sortKey="Angliker, H" uniqKey="Angliker H">H Angliker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thomas, G" uniqKey="Thomas G">G Thomas</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pasquato, A" uniqKey="Pasquato A">A Pasquato</name></author><author><name sortKey="Ramos Da Palma, J" uniqKey="Ramos Da Palma J">J Ramos da Palma</name></author><author><name sortKey="Galan, C" uniqKey="Galan C">C Galan</name></author><author><name sortKey="Seidah, Ng" uniqKey="Seidah N">NG Seidah</name></author><author><name sortKey="Kunz, S" uniqKey="Kunz S">S Kunz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Simmons, G" uniqKey="Simmons G">G Simmons</name></author><author><name sortKey="Reeves, Jd" uniqKey="Reeves J">JD Reeves</name></author><author><name sortKey="Grogan, Cc" uniqKey="Grogan C">CC Grogan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Glowacka, I" uniqKey="Glowacka I">I Glowacka</name></author><author><name sortKey="Bertram, S" uniqKey="Bertram S">S Bertram</name></author><author><name sortKey="Muller, Ma" uniqKey="Muller M">MA Muller</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hofmann, H" uniqKey="Hofmann H">H Hofmann</name></author><author><name sortKey="Simmons, G" uniqKey="Simmons G">G Simmons</name></author><author><name sortKey="Rennekamp, Aj" uniqKey="Rennekamp A">AJ Rennekamp</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Connor, Ri" uniqKey="Connor R">RI Connor</name></author><author><name sortKey="Chen, Bk" uniqKey="Chen B">BK Chen</name></author><author><name sortKey="Choe, S" uniqKey="Choe S">S Choe</name></author><author><name sortKey="Landau, Nr" uniqKey="Landau N">NR Landau</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gao, F" uniqKey="Gao F">F Gao</name></author><author><name sortKey="Li, Y" uniqKey="Li Y">Y Li</name></author><author><name sortKey="Decker, Jm" uniqKey="Decker J">JM Decker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kuhl, A" uniqKey="Kuhl A">A Kühl</name></author><author><name sortKey="Hoffmann, M" uniqKey="Hoffmann M">M Hoffmann</name></author><author><name sortKey="Muller, Ma" uniqKey="Muller M">MA Muller</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></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Corman, Vm" uniqKey="Corman V">VM Corman</name></author><author><name sortKey="Muller, Ma" uniqKey="Muller M">MA Muller</name></author><author><name sortKey="Costabel, U" uniqKey="Costabel U">U Costabel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Becker, Gl" uniqKey="Becker G">GL Becker</name></author><author><name sortKey="Lu, Y" uniqKey="Lu Y">Y Lu</name></author><author><name sortKey="Hardes, K" uniqKey="Hardes K">K Hardes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Volchkov, Ve" uniqKey="Volchkov V">VE Volchkov</name></author><author><name sortKey="Feldmann, H" uniqKey="Feldmann H">H Feldmann</name></author><author><name sortKey="Volchkova, Va" uniqKey="Volchkova V">VA Volchkova</name></author><author><name sortKey="Klenk, Hd" uniqKey="Klenk H">HD Klenk</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lenz, O" uniqKey="Lenz O">O Lenz</name></author><author><name sortKey="Ter Meulen, J" uniqKey="Ter Meulen J">J ter Meulen</name></author><author><name sortKey="Klenk, Hd" uniqKey="Klenk H">HD Klenk</name></author><author><name sortKey="Seidah, Ng" uniqKey="Seidah N">NG Seidah</name></author><author><name sortKey="Garten, W" uniqKey="Garten W">W Garten</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Seidah, Ng" uniqKey="Seidah N">NG Seidah</name></author><author><name sortKey="Prat, A" uniqKey="Prat A">A Prat</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wilson, Ch" uniqKey="Wilson C">CH Wilson</name></author><author><name sortKey="Abbott, Ca" uniqKey="Abbott C">CA Abbott</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Neumann, G" uniqKey="Neumann G">G Neumann</name></author><author><name sortKey="Feldmann, H" uniqKey="Feldmann H">H Feldmann</name></author><author><name sortKey="Watanabe, S" uniqKey="Watanabe S">S Watanabe</name></author><author><name sortKey="Lukashevich, I" uniqKey="Lukashevich I">I Lukashevich</name></author><author><name sortKey="Kawaoka, Y" uniqKey="Kawaoka Y">Y Kawaoka</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Neumann, G" uniqKey="Neumann G">G Neumann</name></author><author><name sortKey="Geisbert, Tw" uniqKey="Geisbert T">TW Geisbert</name></author><author><name sortKey="Ebihara, H" uniqKey="Ebihara H">H Ebihara</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bertram, S" uniqKey="Bertram S">S Bertram</name></author><author><name sortKey="Dijkman, R" uniqKey="Dijkman R">R Dijkman</name></author><author><name sortKey="Habjan, M" uniqKey="Habjan M">M Habjan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kawase, M" uniqKey="Kawase M">M Kawase</name></author><author><name sortKey="Shirato, K" uniqKey="Shirato K">K Shirato</name></author><author><name sortKey="Van Der Hoek, L" uniqKey="Van Der Hoek L">L van der Hoek</name></author><author><name sortKey="Taguchi, F" uniqKey="Taguchi F">F Taguchi</name></author><author><name sortKey="Matsuyama, S" uniqKey="Matsuyama S">S Matsuyama</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shirato, K" uniqKey="Shirato K">K Shirato</name></author><author><name sortKey="Matsuyama, S" uniqKey="Matsuyama S">S Matsuyama</name></author><author><name sortKey="Ujike, M" uniqKey="Ujike M">M Ujike</name></author><author><name sortKey="Taguchi, F" uniqKey="Taguchi F">F Taguchi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, Ts" uniqKey="Kim T">TS Kim</name></author><author><name sortKey="Heinlein, C" uniqKey="Heinlein C">C Heinlein</name></author><author><name sortKey="Hackman, Rc" uniqKey="Hackman R">RC Hackman</name></author><author><name sortKey="Nelson, Ps" uniqKey="Nelson P">PS Nelson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hofmann, H" uniqKey="Hofmann H">H Hofmann</name></author><author><name sortKey="Li, X" uniqKey="Li X">X Li</name></author><author><name sortKey="Zhang, X" uniqKey="Zhang X">X Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alagaili, An" uniqKey="Alagaili A">AN Alagaili</name></author><author><name sortKey="Briese, T" uniqKey="Briese T">T Briese</name></author><author><name sortKey="Mishra, N" uniqKey="Mishra N">N Mishra</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Song, F" uniqKey="Song F">F Song</name></author><author><name sortKey="Fux, R" uniqKey="Fux R">R Fux</name></author><author><name sortKey="Provacia, Lb" uniqKey="Provacia L">LB Provacia</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Haan, Ca" uniqKey="De Haan C">CA de Haan</name></author><author><name sortKey="Stadler, K" uniqKey="Stadler K">K Stadler</name></author><author><name sortKey="Godeke, Gj" uniqKey="Godeke G">GJ Godeke</name></author><author><name sortKey="Bosch, Bj" uniqKey="Bosch B">BJ Bosch</name></author><author><name sortKey="Rottier, Pj" uniqKey="Rottier P">PJ Rottier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Frana, Mf" uniqKey="Frana M">MF Frana</name></author><author><name sortKey="Behnke, Jn" uniqKey="Behnke J">JN Behnke</name></author><author><name sortKey="Sturman, Ls" uniqKey="Sturman L">LS Sturman</name></author><author><name sortKey="Holmes, Kv" uniqKey="Holmes K">KV Holmes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cavanagh, D" uniqKey="Cavanagh D">D Cavanagh</name></author><author><name sortKey="Davis, Pj" uniqKey="Davis P">PJ Davis</name></author><author><name sortKey="Pappin, Dj" uniqKey="Pappin D">DJ Pappin</name></author><author><name sortKey="Binns, Mm" uniqKey="Binns M">MM Binns</name></author><author><name sortKey="Boursnell, Me" uniqKey="Boursnell M">ME Boursnell</name></author><author><name sortKey="Brown, Td" uniqKey="Brown T">TD Brown</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bergeron, E" uniqKey="Bergeron E">E Bergeron</name></author><author><name sortKey="Vincent, Mj" uniqKey="Vincent M">MJ Vincent</name></author><author><name sortKey="Wickham, L" uniqKey="Wickham L">L Wickham</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Follis, Ke" uniqKey="Follis K">KE Follis</name></author><author><name sortKey="York, J" uniqKey="York J">J York</name></author><author><name sortKey="Nunberg, Jh" uniqKey="Nunberg J">JH Nunberg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Simmons, G" uniqKey="Simmons G">G Simmons</name></author><author><name sortKey="Bertram, S" uniqKey="Bertram S">S Bertram</name></author><author><name sortKey="Glowacka, I" uniqKey="Glowacka I">I Glowacka</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Infect Dis</journal-id><journal-id journal-id-type="iso-abbrev">J. Infect. Dis</journal-id><journal-id journal-id-type="publisher-id">jid</journal-id><journal-id journal-id-type="hwp">jinfdis</journal-id><journal-title-group><journal-title>The Journal of Infectious Diseases</journal-title></journal-title-group><issn pub-type="ppub">0022-1899</issn><issn pub-type="epub">1537-6613</issn><publisher><publisher-name>Oxford University Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">25057042</article-id><article-id pub-id-type="pmc">7107327</article-id><article-id pub-id-type="doi">10.1093/infdis/jiu407</article-id><article-id pub-id-type="publisher-id">jiu407</article-id><article-categories><subj-group subj-group-type="heading"><subject>Major Articles and Brief Reports</subject><subj-group subj-group-type="category-toc-heading"><subject>Viruses</subject></subj-group></subj-group></article-categories><title-group><article-title>Inhibition of Proprotein Convertases Abrogates Processing of the Middle Eastern Respiratory Syndrome Coronavirus Spike Protein in Infected Cells but Does Not Reduce Viral Infectivity</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Gierer</surname><given-names>Stefanie</given-names></name><xref ref-type="aff" rid="af1">1</xref><pmc-comment>spoehlmann@dpz.eu </pmc-comment>
<xref ref-type="corresp" rid="d4747e220"></xref></contrib><contrib contrib-type="author"><name><surname>Müller</surname><given-names>Marcel A.</given-names></name><xref ref-type="aff" rid="af2">2</xref></contrib><contrib contrib-type="author"><name><surname>Heurich</surname><given-names>Adeline</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Ritz</surname><given-names>Daniel</given-names></name><xref ref-type="aff" rid="af2">2</xref></contrib><contrib contrib-type="author"><name><surname>Springstein</surname><given-names>Benjamin L.</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Karsten</surname><given-names>Christina B.</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="aff" rid="af3">3</xref></contrib><contrib contrib-type="author"><name><surname>Schendzielorz</surname><given-names>Alexander</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Gnirß</surname><given-names>Kerstin</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Drosten</surname><given-names>Christian</given-names></name><xref ref-type="aff" rid="af2">2</xref></contrib><contrib contrib-type="author"><name><surname>Pöhlmann</surname><given-names>Stefan</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib></contrib-group><aff id="af1"><label>1</label><addr-line>Infection Biology Unit</addr-line>,<institution>German Primate Center</institution>,<addr-line>Göttingen</addr-line></aff><aff id="af2"><label>2</label><addr-line>Institute of Virology</addr-line>,<institution>University of Bonn Medical Center</institution></aff><aff id="af3"><label>3</label><addr-line>Institute for Cellular Chemistry</addr-line>,<institution>Hannover Medical School</institution>,<country>Germany</country></aff><author-notes><fn id="TN1" fn-type="con"><p>Presented in part: 7th European Meeting on Viral Zoonoses, St. Raphaël, France, 24–27 May 2014.</p></fn><corresp id="d4747e220">Correspondence: Stefan Pöhlmann, PhD, Infection Biology Unit, German Primate Center, Kellnerweg 4, 37077 Göttingen, Germany (<email>spoehlmann@dpz.eu</email>).</corresp></author-notes><pub-date pub-type="ppub"><day>15</day><month>3</month><year>2015</year></pub-date><pub-date pub-type="epub" iso-8601-date="2014-07-23"><day>23</day><month>7</month><year>2014</year></pub-date><volume>211</volume><issue>6</issue><fpage>889</fpage><lpage>897</lpage><history><date date-type="received"><day>23</day><month>4</month><year>2014</year></date><date date-type="accepted"><day>10</day><month>7</month><year>2014</year></date></history><permissions><copyright-statement>© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: <email>journals.permissions@oup.com</email>.</copyright-statement><copyright-year>2014</copyright-year><license><license-p>This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.</license-p></license></permissions><self-uri xlink:href="jiu407.pdf"></self-uri><abstract><title>Abstract</title><p>Middle East respiratory syndrome coronavirus (MERS-CoV) infection is associated with a high case-fatality rate, and the potential pandemic spread of the virus is a public health concern. The spike protein of MERS-CoV (MERS-S) facilitates viral entry into host cells, which depends on activation of MERS-S by cellular proteases. Proteolytic activation of MERS-S during viral uptake into target cells has been demonstrated. However, it is unclear whether MERS-S is also cleaved during S protein synthesis in infected cells and whether cleavage is required for MERS-CoV infectivity. Here, we show that MERS-S is processed by proprotein convertases in MERS-S–transfected and MERS-CoV–infected cells and that several RXXR motifs located at the border between the surface and transmembrane subunit of MERS-S are required for efficient proteolysis. However, blockade of proprotein convertases did not impact MERS-S–dependent transduction of target cells expressing high amounts of the viral receptor, DPP4, and did not modulate MERS-CoV infectivity. These results show that MERS-S is a substrate for proprotein convertases and demonstrate that processing by these enzymes is dispensable for S protein activation. Efforts to inhibit MERS-CoV infection by targeting host cell proteases should therefore focus on enzymes that process MERS-S during viral uptake into target cells.</p></abstract><kwd-group><kwd>MERS-coronavirus</kwd><kwd>protease</kwd><kwd>TMPRSS2</kwd><kwd>trypsin</kwd><kwd>proprotein convertase</kwd><kwd>spike</kwd><kwd>activation</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/MersV1/Data/Pmc/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000E22 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd -nk 000E22 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= MersV1
|flux= Pmc
|étape= Curation
|type= RBID
|clé= PMC:7107327
|texte= Inhibition of Proprotein Convertases Abrogates Processing of the Middle Eastern Respiratory Syndrome Coronavirus Spike Protein in Infected Cells but Does Not Reduce Viral Infectivity
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Curation/RBID.i -Sk "pubmed:25057042" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd \
| NlmPubMed2Wicri -a MersV1
| This area was generated with Dilib version V0.6.33. |  |