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3. Rapid reconstruction of SARS-CoV-2 using a synthetic genomics platform

Author

Thi Nhu Thao, Tran, Labroussaa, Fabien, Ebert, Nadine, V’kovski, Philip, Stalder, Hanspeter, Portmann, Jasmine, Kelly, Jenna, Steiner, Silvio, Holwerda, Melle, Kratzel, Annika, Gultom, Mitra, Schmied, Kimberly, Laloli, Laura, Hüsser, Linda, Wider, Manon, Pfaender, Stephanie, Hirt, Dagny, Cippà, Valentina, Crespo-Pomar, Silvia, Schröder, Simon, Muth, Doreen, Niemeyer, Daniela, Corman, Victor M., Müller, Marcel A., Drosten, Christian, Dijkman, Ronald, Jores, Joerg, and Thiel, Volker

Published
2020
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4. Functional comparison of MERS-coronavirus lineages reveals increased replicative fitness of the recombinant lineage 5

Author

Schroeder, Simon, Mache, Christin, Kleine-Weber, Hannah, Corman, Victor M., Muth, Doreen, Richter, Anja, Fatykhova, Diana, Memish, Ziad A., Stanifer, Megan L., Boulant, Steeve, Gultom, Mitra, Dijkman, Ronald, Eggeling, Stephan, Hocke, Andreas, Hippenstiel, Stefan, Thiel, Volker, Pöhlmann, Stefan, Wolff, Thorsten, Müller, Marcel A., and Drosten, Christian

Published
2021
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5. MERS coronaviruses from camels in Africa exhibit region-dependent genetic diversity

Author

Chu, Daniel K. W., Hui, Kenrie P. Y., Perera, Ranawaka A. P. M., Miguel, Eve, Niemeyer, Daniela, Zhao, Jincun, Channappanavar, Rudragouda, Dudas, Gytis, Oladipo, Jamiu O., Traoré, Amadou, Fassi-Fihri, Ouafaa, Ali, Abraham, Demissié, Getnet F., Muth, Doreen, Chan, Michael C. W., Nicholls, John M., Meyerholz, David K., Kuranga, Sulyman A., Mamo, Gezahegne, Zhou, Ziqi, So, Ray T. Y., Hemida, Maged G., Webby, Richard J., Roger, Francois, Rambaut, Andrew, Poon, Leo L. M., Perlman, Stanley, Drosten, Christian, Chevalier, Veronique, and Peiris, Malik

Published
2018

7. SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection

Author

Gassen, Nils C., Niemeyer, Daniela, Muth, Doreen, Corman, Victor M., Martinelli, Silvia, Gassen, Alwine, Hafner, Kathrin, Papies, Jan, Mösbauer, Kirstin, Zellner, Andreas, Zannas, Anthony S., Herrmann, Alexander, Holsboer, Florian, Brack-Werner, Ruth, Boshart, Michael, Müller-Myhsok, Bertram, Drosten, Christian, Müller, Marcel A., and Rein, Theo

Published
2019
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11. Attenuation of replication by a 29 nucleotide deletion in SARS-coronavirus acquired during the early stages of human-to-human transmission

Author

Muth, Doreen, Corman, Victor Max, Roth, Hanna, Binger, Tabea, Dijkman, Ronald, Gottula, Lina Theresa, Gloza-Rausch, Florian, Balboni, Andrea, Battilani, Mara, Rihtarič, Danijela, Toplak, Ivan, Ameneiros, Ramón Seage, Pfeifer, Alexander, Thiel, Volker, Drexler, Jan Felix, Müller, Marcel Alexander, and Drosten, Christian

Published
2018
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12. Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study

Author

Reusken, Chantal BEM, Haagmans, Bart L, Müller, Marcel A, Gutierrez, Carlos, Godeke, Gert-Jan, Meyer, Benjamin, Muth, Doreen, Raj, V Stalin, Vries, Laura Smits-De, Corman, Victor M, Drexler, Jan-Felix, Smits, Saskia L, El Tahir, Yasmin E, De Sousa, Rita, van Beek, Janko, Nowotny, Norbert, van Maanen, Kees, Hidalgo-Hermoso, Ezequiel, Bosch, Berend-Jan, Rottier, Peter, Osterhaus, Albert, Gortázar-Schmidt, Christian, Drosten, Christian, and Koopmans, Marion PG

Published
2013
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13. Clinical features and virological analysis of a case of Middle East respiratory syndrome coronavirus infection

Author

Drosten, Christian, Seilmaier, Michael, Corman, Victor M, Hartmann, Wulf, Scheible, Gregor, Sack, Stefan, Guggemos, Wolfgang, Kallies, Rene, Muth, Doreen, Junglen, Sandra, Müller, Marcel A, Haas, Walter, Guberina, Hana, Röhnisch, Tim, Schmid-Wendtner, Monika, Aldabbagh, Souhaib, Dittmer, Ulf, Gold, Hermann, Graf, Petra, Bonin, Frank, Rambaut, Andrew, and Wendtner, Clemens-Martin

Published
2013
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15. Acute Middle East respiratory syndrome coronavirus infection in livestock dromedaries, Dubai, 2014

Author

Wernery, Ulrich, Corman, Victor M., Wong, Emily Y.M., Tsang, Alan K.L., Muth, Doreen, Lau, Susanna K.P., Khazanehdari, Kamal, Zirkel, Florian, Ali, Mansoor, Nagy, Peter, Juhasz, Jutka, Wernery, Renate, Joseph, Sunitha, Syriac, Ginu, Elizabeth, Shyna K., Patteril, Nissy Annie Georgy, Woo, Patrick C.Y., and Drosten, Christian

Subjects
Coronaviruses -- Identification and classification -- Health aspects, Livestock -- Diseases -- Medical examination, Company distribution practices, Health
Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) causes outbreaks and isolated cases of severe respiratory disease in humans. The virus is transmissible from human to human, but the focus of infection [...]

Published
2015
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16. Temporal and spatial analysis of the 2014–2015 Ebola virus outbreak in West Africa

Author

Carroll, Miles W., Matthews, David A., Hiscox, Julian A., Elmore, Michael J., Pollakis, Georgios, Rambaut, Andrew, Hewson, Roger, García-Dorival, Isabel, Bore, Joseph Akoi, Koundouno, Raymond, Abdellati, Saïd, Afrough, Babak, Aiyepada, John, Akhilomen, Patience, Asogun, Danny, Atkinson, Barry, Badusche, Marlis, Bah, Amadou, Bate, Simon, Baumann, Jan, Becker, Dirk, Becker-Ziaja, Beate, Bocquin, Anne, Borremans, Benny, Bosworth, Andrew, Boettcher, Jan Peter, Cannas, Angela, Carletti, Fabrizio, Castilletti, Concetta, Clark, Simon, Colavita, Francesca, Diederich, Sandra, Donatus, Adomeh, Duraffour, Sophie, Ehichioya, Deborah, Ellerbrok, Heinz, Fernandez-Garcia, Maria Dolores, Fizet, Alexandra, Fleischmann, Erna, Gryseels, Sophie, Hermelink, Antje, Hinzmann, Julia, Hopf-Guevara, Ute, Ighodalo, Yemisi, Jameson, Lisa, Kelterbaum, Anne, Kis, Zoltan, Kloth, Stefan, Kohl, Claudia, Korva, Miša, Kraus, Annette, Kuisma, Eeva, Kurth, Andreas, Liedigk, Britta, Logue, Christopher H., Lüdtke, Anja, Maes, Piet, McCowen, James, Mély, Stéphane, Mertens, Marc, Meschi, Silvia, Meyer, Benjamin, Michel, Janine, Molkenthin, Peter, Muñoz-Fontela, César, Muth, Doreen, Newman, Edmund N. C., Ngabo, Didier, Oestereich, Lisa, Okosun, Jennifer, Olokor, Thomas, Omiunu, Racheal, Omomoh, Emmanuel, Pallasch, Elisa, Pályi, Bernadett, Portmann, Jasmine, Pottage, Thomas, Pratt, Catherine, Priesnitz, Simone, Quartu, Serena, Rappe, Julie, Repits, Johanna, Richter, Martin, Rudolf, Martin, Sachse, Andreas, Schmidt, Kristina Maria, Schudt, Gordian, Strecker, Thomas, Thom, Ruth, Thomas, Stephen, Tobin, Ekaete, Tolley, Howard, Trautner, Jochen, Vermoesen, Tine, Vitoriano, Inês, Wagner, Matthias, Wolff, Svenja, Yue, Constanze, Capobianchi, Maria Rosaria, Kretschmer, Birte, Hall, Yper, Kenny, John G., Rickett, Natasha Y., Dudas, Gytis, Coltart, Cordelia E. M., Kerber, Romy, Steer, Damien, Wright, Callum, Senyah, Francis, Keita, Sakoba, Drury, Patrick, Diallo, Boubacar, de Clerck, Hilde, Van Herp, Michel, Sprecher, Armand, Traore, Alexis, Diakite, Mandiou, Konde, Mandy Kader, Koivogui, Lamine, Magassouba, N’Faly, Avšič-Županc, Tatjana, Nitsche, Andreas, Strasser, Marc, Ippolito, Giuseppe, Becker, Stephan, Stoecker, Kilian, Gabriel, Martin, Raoul, Hervé, Di Caro, Antonino, Wölfel, Roman, Formenty, Pierre, and Günther, Stephan

Published
2015
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17. Antibodies against MERS Coronavirus in dromedaries, United Arab Emirates, 2003 and 2013

Author

Meyer, Benjamin, Muller, Marcel A., Corman, Victor M., Reusken, Chantal B.E.M., Ritz, Daniel, Godeke, Gert-Jan, Lattwein, Erik, Kallies, Stephan, Siemens, Artem, van Beek, Janko, Drexler, Jan F., Muth, Doreen, Bosch, Berend-Jan, Wernery, Ulrich, Koopmans, Marion P.G., Wernery, Renate, and Drosten, Christian

Subjects
Viral antibodies -- Health aspects -- Analysis, Antibodies -- Health aspects -- Analysis, Health
Abstract

Middle East respiratory syndrome coronavirus (MERSCoV) is an emerging pathogen associated with severe respiratory symptoms and renal failure in infected patients (1,2). Globally, 156 laboratory-confirmed cases of infection with MERS-CoV, [...]

Published
2014
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18. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC

Author

Raj, V. Stalin, Mou, Huihui, Smits, Saskia L., Dekkers, Dick H.W., Muller, Marcel A., Dijkman, Ronald, Muth, Doreen, Demmers, Jeroen A.A., Zaki, Ali, Fouchier, Ron A.M., Thiel, Volker, Drosten, Christian, Rottier, Peter J.M., Osterhaus, Albert D.M.E., Bosch, Berend Jan, and Haagmans, Bart L.

Subjects
Coronavirus infections -- Diagnosis -- Complications and side effects -- Causes of, Medical research, Medicine, Experimental, Ubiquitin-proteasome system -- Research, Proteases -- Physiological aspects, Coronaviruses -- Physiological aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Most human coronaviruses cause mild upper respiratory tract disease but may be associated with more severe pulmonary disease in immunocompromised individuals (1). However, SARS coronavirus caused severe lower respiratory disease with nearly 10% mortality and evidence of systemic spread (2). Recently, another coronavirus (human coronavirus-Erasmus Medical Center (hCoV-EMC)) was identified in patients with severe and sometimes lethal lower respiratory tract infection (3'4). Viral genome analysis revealed close relatedness to coronaviruses found in bats (5). Here we identify dipeptidyl peptidase 4 (DPP4; also known as CD26) as a functional receptor for hCoV-EMC. DPP4 specifically co-purified with the receptor-binding S1 domain of the hCoV-EMC spike protein from lysates of susceptible Huh-7 cells. Antibodies directed against DPP4 inhibited hCoV-EMC infection of primary human bronchial epithelial cells and Huh-7 cells. Expression of human and bat (Pipistrellus pipistrellus) DPP4 in non-susceptible COS-7 cells enabled infection by hCoV-EMC. The use of the evolutionarily conserved DPP4 protein from different species as a functional receptor provides clues about the host range potential of hCoV-EMC. In addition, it will contribute critically to our understanding of the pathogenesis and epidemiology of this emerging human coronavirus, and may facilitate the development of intervention strategies., Coronaviruses infect a wide range of mammals and birds. Their tropism is primarily determined by the ability of the spike (S) entry protein to bind to a cell surface receptor. [...]

Published
2013

19. Human parvovirus 4 in nasal and fecal specimens from children, Ghana

Author

Drexler, Jan Felix, Reber, Ulrike, Muth, Doreen, Herzog, Petra, Annan, Augustina, Ebach, Fabian, Sarpong, Nimarko, Acquah, Samuel, Adlkofer, Julia, Adu-Sarkodie, Yaw, Panning, Marcus, Tannich, Egbert, May, Jurgen, Drosten, Christian, and Eis-Hubinger, Anna Maria

Subjects
Parvovirus infections -- Risk factors -- Research -- Diagnosis, Children -- Health aspects, Disease transmission -- Research, Health
Abstract

Nonparenteral transmission might contribute to human parvovirus 4 (PARV4) infections in sub-Saharan Africa. PARV4 DNA was detected in 8 (0.83%) of 961 nasal samples and 5 (0.53%) of 943 fecal [...]

Published
2012
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21. Functional comparison of MERS-coronavirus lineages reveals increased zoonotic potential of the recombinant lineage 5

Author

Schroeder, Simon, primary, Mache, Christin, additional, Kleine-Weber, Hannah, additional, Muth, Doreen, additional, Corman, Victor, additional, Fatykhova, Diana, additional, Memish, Ziad Al, additional, Stanifer, Megan, additional, Boulant, Steeve, additional, Dijkman, Ronald, additional, Richter, Anja, additional, Eggeling, Stefan, additional, Hocke, Andreas, additional, Hippenstiel, Stefan, additional, Thiel, Volker, additional, Pöhlmann, Stefan, additional, Wolff, Thorsten, additional, Müller, Marcel, additional, and Drosten, Christian, additional

Published
2020
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22. Rapid reconstruction of SARS-CoV-2 using a synthetic genomics platform

Author

Nhu Thao, Tran Thi, primary, Labroussaa, Fabien, additional, Ebert, Nadine, additional, V’kovski, Philip, additional, Stalder, Hanspeter, additional, Portmann, Jasmine, additional, Kelly, Jenna, additional, Steiner, Silvio, additional, Holwerda, Melle, additional, Kratzel, Annika, additional, Gultom, Mitra, additional, Laloli, Laura, additional, Hüsser, Linda, additional, Wider, Manon, additional, Pfaender, Stephanie, additional, Hirt, Dagny, additional, Cippà, Valentina, additional, Crespo-Pomar, Silvia, additional, Schröder, Simon, additional, Muth, Doreen, additional, Niemeyer, Daniela, additional, Müller, Marcel A., additional, Drosten, Christian, additional, Dijkman, Ronald, additional, Jores, Joerg, additional, and Thiel, Volker, additional

Published
2020
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24. One-step selection of Vaccinia virus-binding DNA aptamers by MonoLEX

Author

Stöcklein Walter, Scheller Frieder, Muth Doreen, Junge Wolfgang, Sielaff Hendrik, Pänke Oliver, Dunkhorst Anna, Kurth Andreas, Nitsche Andreas, Dahmen Claudia, Pauli Georg, and Kage Andreas

Subjects
Biotechnology, TP248.13-248.65
Abstract

Abstract Background As a new class of therapeutic and diagnostic reagents, more than fifteen years ago RNA and DNA aptamers were identified as binding molecules to numerous small compounds, proteins and rarely even to complete pathogen particles. Most aptamers were isolated from complex libraries of synthetic nucleic acids by a process termed SELEX based on several selection and amplification steps. Here we report the application of a new one-step selection method (MonoLEX) to acquire high-affinity DNA aptamers binding Vaccinia virus used as a model organism for complex target structures. Results The selection against complete Vaccinia virus particles resulted in a 64-base DNA aptamer specifically binding to orthopoxviruses as validated by dot blot analysis, Surface Plasmon Resonance, Fluorescence Correlation Spectroscopy and real-time PCR, following an aptamer blotting assay. The same oligonucleotide showed the ability to inhibit in vitro infection of Vaccinia virus and other orthopoxviruses in a concentration-dependent manner. Conclusion The MonoLEX method is a straightforward procedure as demonstrated here for the identification of a high-affinity DNA aptamer binding Vaccinia virus. MonoLEX comprises a single affinity chromatography step, followed by subsequent physical segmentation of the affinity resin and a single final PCR amplification step of bound aptamers. Therefore, this procedure improves the selection of high affinity aptamers by reducing the competition between aptamers of different affinities during the PCR step, indicating an advantage for the single-round MonoLEX method.

Published
2007
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25. Antibodies against MERS Coronavirus in Dromedary Camels, United Arab Emirates, 2003 and 2013

Author

Meyer, Benjamin, Müller, Marcel A., Corman, Victor M., Reusken, Chantal B E M, Ritz, Daniel, Godeke, Gert Jan, Lattwein, Erik, Kallies, Stephan, Siemens, Artem, van Beek, Janko, Drexler, Jan F., Muth, Doreen, Bosch, Berend Jan, Wernery, Ulrich, Koopmans, Marion P G, Wernery, Renate, Drosten, Christian, LS Virologie, I&I SIB1, Strategic Infection Biology, LS Virologie, I&I SIB1, Strategic Infection Biology, and Virology

Subjects
Microbiology (medical), endocrine system, Camelus, Epidemiology, Middle East respiratory syndrome coronavirus, viruses, Expedited, coronavirus, lcsh:Medicine, United Arab Emirates, medicine.disease_cause, Antibodies, Viral, Virus, Serology, lcsh:Infectious and parasitic diseases, Antibodies against MERS Coronavirus in Dromedary Camels, United Arab Emirates, 2003 and 2013, MERS-CoV, MERS, Neutralization Tests, medicine, camels, antibodies, Animals, lcsh:RC109-216, serologic analysis, Respiratory Tract Infections, Coronavirus, Respiratory tract infections, business.industry, Research, Middle East respiratory syndrome, lcsh:R, Antibody titer, Outbreak, dromedary camels, Syndrome, medicine.disease, Virology, Antibodies, Neutralizing, 3. Good health, Infectious Diseases, business, Coronavirus Infections
Abstract

Camels were infected with this virus >10 years before the first human cases., Middle East respiratory syndrome coronavirus (MERS-CoV) has caused an ongoing outbreak of severe acute respiratory tract infection in humans in the Arabian Peninsula since 2012. Dromedary camels have been implicated as possible viral reservoirs. We used serologic assays to analyze 651 dromedary camel serum samples from the United Arab Emirates; 151 of 651 samples were obtained in 2003, well before onset of the current epidemic, and 500 serum samples were obtained in 2013. Recombinant spike protein–specific immunofluorescence and virus neutralization tests enabled clear discrimination between MERS-CoV and bovine CoV infections. Most (632/651, 97.1%) camels had antibodies against MERS-CoV. This result included all 151 serum samples obtained in 2003. Most (389/651, 59.8%) serum samples had MERS-CoV–neutralizing antibody titers >1,280. Dromedary camels from the United Arab Emirates were infected at high rates with MERS-CoV or a closely related, probably conspecific, virus long before the first human MERS cases.

Published
2014

26. MERS coronaviruses from camels in Africa exhibit region-dependent genetic diversity

Author

Chu, Daniel K.W., Hui, Kenrie P.Y., Perera, Ranawaka A.P.M., Miguel, Eve, Niemeyer, Daniela, Zhao, Jincun, Channappanavar, Rudragouda, Dudas, Gytis, Oladipo, Jamiu O., Traoré, Amadou, Fassi-Fihri, Ouafaa, Ali, Abraham, Demissie, Getnet Fekadu, Muth, Doreen, Chan, Michael C.W., Nicholls, John M., Meyerholz, David K., Kuranga, Sulyman A., Mamo, Gezahegne, Zhou, Ziqi, So, Ray T.Y., Hemida, Maged G., Webby, Richard J., Roger, François, Rambaut, Andrew, Poon, Leo L.M., Perlman, Stanley, Drosten, Christian, Chevalier, Véronique, Peiris, Malik, Chu, Daniel K.W., Hui, Kenrie P.Y., Perera, Ranawaka A.P.M., Miguel, Eve, Niemeyer, Daniela, Zhao, Jincun, Channappanavar, Rudragouda, Dudas, Gytis, Oladipo, Jamiu O., Traoré, Amadou, Fassi-Fihri, Ouafaa, Ali, Abraham, Demissie, Getnet Fekadu, Muth, Doreen, Chan, Michael C.W., Nicholls, John M., Meyerholz, David K., Kuranga, Sulyman A., Mamo, Gezahegne, Zhou, Ziqi, So, Ray T.Y., Hemida, Maged G., Webby, Richard J., Roger, François, Rambaut, Andrew, Poon, Leo L.M., Perlman, Stanley, Drosten, Christian, Chevalier, Véronique, and Peiris, Malik

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) causes a zoonotic respiratory disease of global public health concern, and dromedary camels are the only proven source of zoonotic infection. Although MERS-CoV infection is ubiquitous in dromedaries across Africa as well as in the Arabian Peninsula, zoonotic disease appears confined to the Arabian Peninsula. MERS-CoVs from Africa have hitherto been poorly studied. We genetically and phenotypically characterized MERS-CoV from dromedaries sampled in Morocco, Burkina Faso, Nigeria, and Ethiopia. Viruses from Africa (clade C) are phylogenetically distinct from contemporary viruses from the Arabian Peninsula (clades A and B) but remain antigenically similar in microneutralization tests. Viruses from West (Nigeria, Burkina Faso) and North (Morocco) Africa form a subclade, C1, that shares clade-defining genetic signatures including deletions in the accessory gene ORF4b. Compared with human and camel MERS-CoV from Saudi Arabia, virus isolates from Burkina Faso (BF785) and Nigeria (Nig1657) had lower virus replication competence in Calu-3 cells and in ex vivo cultures of human bronchus and lung. BF785 replicated to lower titer in lungs of human DPP4-transduced mice. A reverse genetics-derived recombinant MERS-CoV (EMC) lacking ORF4b elicited higher type I and III IFN responses than the isogenic EMC virus in Calu-3 cells. However, ORF4b deletions may not be the major determinant of the reduced replication competence of BF785 and Nig1657. Genetic and phenotypic differences in West African viruses may be relevant to zoonotic potential. There is an urgent need for studies of MERS-CoV at the animal–human interface. Middle East respiratory syndrome (MERS) remains a disease of global public health concern (1). Many human infections are zoonotic in origin, but some result from clusters of human-to-human transmission, especially within hospitals and health care facilities (2). Zoonotic disease has been reported from the Arabian

Published
2018

28. Viral Shedding and Antibody Response in 37 Patients With Middle East Respiratory Syndrome Coronavirus Infection

Author

Corman, Victor M., primary, Albarrak, Ali M., additional, Omrani, Ali Senosi, additional, Albarrak, Mohammed M., additional, Farah, Mohamed Elamin, additional, Almasri, Malak, additional, Muth, Doreen, additional, Sieberg, Andrea, additional, Meyer, Benjamin, additional, Assiri, Abdullah M., additional, Binger, Tabea, additional, Steinhagen, Katja, additional, Lattwein, Erik, additional, Al-Tawfiq, Jaffar, additional, Müller, Marcel A., additional, Drosten, Christian, additional, and Memish, Ziad A., additional

Published
2015
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29. Infectious Middle East Respiratory Syndrome Coronavirus Excretion and Serotype Variability Based on Live Virus Isolates from Patients in Saudi Arabia

Author

Muth, Doreen, primary, Corman, Victor M., additional, Meyer, Benjamin, additional, Assiri, Abdullah, additional, Al-Masri, Malak, additional, Farah, Mohamed, additional, Steinhagen, Katja, additional, Lattwein, Erik, additional, Al-Tawfiq, Jaffar A., additional, Albarrak, Ali, additional, Müller, Marcel A., additional, Drosten, Christian, additional, and Memish, Ziad A., additional

Published
2015
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30. Antibodies against MERS coronavirus in dromedaries, United Arab Emirates, 2003 and 2013

Author

LS Virologie, I&I SIB1, Strategic Infection Biology, Meyer, Benjamin, Müller, Marcel A., Corman, Victor M., Reusken, Chantal B E M, Ritz, Daniel, Godeke, Gert Jan, Lattwein, Erik, Kallies, Stephan, Siemens, Artem, van Beek, Janko, Drexler, Jan F., Muth, Doreen, Bosch, Berend Jan, Wernery, Ulrich, Koopmans, Marion P G, Wernery, Renate, Drosten, Christian, LS Virologie, I&I SIB1, Strategic Infection Biology, Meyer, Benjamin, Müller, Marcel A., Corman, Victor M., Reusken, Chantal B E M, Ritz, Daniel, Godeke, Gert Jan, Lattwein, Erik, Kallies, Stephan, Siemens, Artem, van Beek, Janko, Drexler, Jan F., Muth, Doreen, Bosch, Berend Jan, Wernery, Ulrich, Koopmans, Marion P G, Wernery, Renate, and Drosten, Christian

Published
2014

31. An Observational, Laboratory-Based Study of Outbreaks of Middle East Respiratory Syndrome Coronavirus in Jeddah and Riyadh, Kingdom of Saudi Arabia, 2014

Author

Drosten, Christian, primary, Muth, Doreen, primary, Corman, Victor M., primary, Hussain, Raheela, primary, Al Masri, Malaki, primary, HajOmar, Waleed, primary, Landt, Olfert, primary, Assiri, Abdullah, primary, Eckerle, Isabella, primary, Al Shangiti, Ali, primary, Al-Tawfiq, Jaffar A., primary, Albarrak, Ali, primary, Zumla, Alimuddin, primary, Rambaut, Andrew, primary, and Memish, Ziad A., primary

Published
2014
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32. Targeting Membrane-Bound Viral RNA Synthesis Reveals Potent Inhibition of Diverse Coronaviruses Including the Middle East Respiratory Syndrome Virus

Author

Lundin, Anna, primary, Dijkman, Ronald, additional, Bergström, Tomas, additional, Kann, Nina, additional, Adamiak, Beata, additional, Hannoun, Charles, additional, Kindler, Eveline, additional, Jónsdóttir, Hulda R., additional, Muth, Doreen, additional, Kint, Joeri, additional, Forlenza, Maria, additional, Müller, Marcel A., additional, Drosten, Christian, additional, Thiel, Volker, additional, and Trybala, Edward, additional

Published
2014
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33. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC

Author

Raj, V Stalin, Mou, Huihui, Smits, Saskia L, Dekkers, Dick H W, Müller, Marcel A, Dijkman, Ronald, Muth, Doreen, Demmers, Jeroen A A, Zaki, Ali, Fouchier, Ron A M, Thiel, Volker, Drosten, Christian, Rottier, Peter J M, Osterhaus, Albert D M E, Bosch, Berend Jan, Haagmans, Bart L, Raj, V Stalin, Mou, Huihui, Smits, Saskia L, Dekkers, Dick H W, Müller, Marcel A, Dijkman, Ronald, Muth, Doreen, Demmers, Jeroen A A, Zaki, Ali, Fouchier, Ron A M, Thiel, Volker, Drosten, Christian, Rottier, Peter J M, Osterhaus, Albert D M E, Bosch, Berend Jan, and Haagmans, Bart L

Abstract

Most human coronaviruses cause mild upper respiratory tract disease but may be associated with more severe pulmonary disease in immunocompromised individuals. However, SARS coronavirus caused severe lower respiratory disease with nearly 10% mortality and evidence of systemic spread. Recently, another coronavirus (human coronavirus-Erasmus Medical Center (hCoV-EMC)) was identified in patients with severe and sometimes lethal lower respiratory tract infection. Viral genome analysis revealed close relatedness to coronaviruses found in bats. Here we identify dipeptidyl peptidase 4 (DPP4; also known as CD26) as a functional receptor for hCoV-EMC. DPP4 specifically co-purified with the receptor-binding S1 domain of the hCoV-EMC spike protein from lysates of susceptible Huh-7 cells. Antibodies directed against DPP4 inhibited hCoV-EMC infection of primary human bronchial epithelial cells and Huh-7 cells. Expression of human and bat (Pipistrellus pipistrellus) DPP4 in non-susceptible COS-7 cells enabled infection by hCoV-EMC. The use of the evolutionarily conserved DPP4 protein from different species as a functional receptor provides clues about the host range potential of hCoV-EMC. In addition, it will contribute critically to our understanding of the pathogenesis and epidemiology of this emerging human coronavirus, and may facilitate the development of intervention strategies.

Published
2013

34. Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study

Author

Reusken, Chantal B E M, Haagmans, Bart L, Müller, Marcel A, Gutierrez, Carlos, Godeke, Gert-Jan, Meyer, Benjamin, Muth, Doreen, Raj, V Stalin, Smits-De Vries, Laura, Corman, Victor M, Drexler, Jan-Felix, Smits, Saskia L, El Tahir, Yasmin E, De Sousa, Rita, van Beek, Janko, Nowotny, Norbert, van Maanen, Kees, Hidalgo-Hermoso, Ezequiel, Bosch, Berend-Jan, Rottier, Peter, Osterhaus, Albert, Gortázar-Schmidt, Christian, Drosten, Christian, Koopmans, Marion P G, Reusken, Chantal B E M, Haagmans, Bart L, Müller, Marcel A, Gutierrez, Carlos, Godeke, Gert-Jan, Meyer, Benjamin, Muth, Doreen, Raj, V Stalin, Smits-De Vries, Laura, Corman, Victor M, Drexler, Jan-Felix, Smits, Saskia L, El Tahir, Yasmin E, De Sousa, Rita, van Beek, Janko, Nowotny, Norbert, van Maanen, Kees, Hidalgo-Hermoso, Ezequiel, Bosch, Berend-Jan, Rottier, Peter, Osterhaus, Albert, Gortázar-Schmidt, Christian, Drosten, Christian, and Koopmans, Marion P G

Abstract

BACKGROUND: A new betacoronavirus-Middle East respiratory syndrome coronavirus (MERS-CoV)-has been identified in patients with severe acute respiratory infection. Although related viruses infect bats, molecular clock analyses have been unable to identify direct ancestors of MERS-CoV. Anecdotal exposure histories suggest that patients had been in contact with dromedary camels or goats. We investigated possible animal reservoirs of MERS-CoV by assessing specific serum antibodies in livestock.METHODS: We took sera from animals in the Middle East (Oman) and from elsewhere (Spain, Netherlands, Chile). Cattle (n=80), sheep (n=40), goats (n=40), dromedary camels (n=155), and various other camelid species (n=34) were tested for specific serum IgG by protein microarray using the receptor-binding S1 subunits of spike proteins of MERS-CoV, severe acute respiratory syndrome coronavirus, and human coronavirus OC43. Results were confirmed by virus neutralisation tests for MERS-CoV and bovine coronavirus.FINDINGS: 50 of 50 (100%) sera from Omani camels and 15 of 105 (14%) from Spanish camels had protein-specific antibodies against MERS-CoV spike. Sera from European sheep, goats, cattle, and other camelids had no such antibodies. MERS-CoV neutralising antibody titres varied between 1/320 and 1/2560 for the Omani camel sera and between 1/20 and 1/320 for the Spanish camel sera. There was no evidence for cross-neutralisation by bovine coronavirus antibodies.INTERPRETATION: MERS-CoV or a related virus has infected camel populations. Both titres and seroprevalences in sera from different locations in Oman suggest widespread infection.FUNDING: European Union, European Centre For Disease Prevention and Control, Deutsche Forschungsgemeinschaft.

Published
2013

35. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC

Author

LS Virologie, Bedrijfsvoering, Raj, V Stalin, Mou, Huihui, Smits, Saskia L, Dekkers, Dick H W, Müller, Marcel A, Dijkman, Ronald, Muth, Doreen, Demmers, Jeroen A A, Zaki, Ali, Fouchier, Ron A M, Thiel, Volker, Drosten, Christian, Rottier, Peter J M, Osterhaus, Albert D M E, Bosch, Berend Jan, Haagmans, Bart L, LS Virologie, Bedrijfsvoering, Raj, V Stalin, Mou, Huihui, Smits, Saskia L, Dekkers, Dick H W, Müller, Marcel A, Dijkman, Ronald, Muth, Doreen, Demmers, Jeroen A A, Zaki, Ali, Fouchier, Ron A M, Thiel, Volker, Drosten, Christian, Rottier, Peter J M, Osterhaus, Albert D M E, Bosch, Berend Jan, and Haagmans, Bart L

Published
2013

36. Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study

Author

LS Virologie, Reusken, Chantal B E M, Haagmans, Bart L, Müller, Marcel A, Gutierrez, Carlos, Godeke, Gert-Jan, Meyer, Benjamin, Muth, Doreen, Raj, V Stalin, Smits-De Vries, Laura, Corman, Victor M, Drexler, Jan-Felix, Smits, Saskia L, El Tahir, Yasmin E, De Sousa, Rita, van Beek, Janko, Nowotny, Norbert, van Maanen, Kees, Hidalgo-Hermoso, Ezequiel, Bosch, Berend-Jan, Rottier, Peter, Osterhaus, Albert, Gortázar-Schmidt, Christian, Drosten, Christian, Koopmans, Marion P G, LS Virologie, Reusken, Chantal B E M, Haagmans, Bart L, Müller, Marcel A, Gutierrez, Carlos, Godeke, Gert-Jan, Meyer, Benjamin, Muth, Doreen, Raj, V Stalin, Smits-De Vries, Laura, Corman, Victor M, Drexler, Jan-Felix, Smits, Saskia L, El Tahir, Yasmin E, De Sousa, Rita, van Beek, Janko, Nowotny, Norbert, van Maanen, Kees, Hidalgo-Hermoso, Ezequiel, Bosch, Berend-Jan, Rottier, Peter, Osterhaus, Albert, Gortázar-Schmidt, Christian, Drosten, Christian, and Koopmans, Marion P G

Published
2013

38. Efficient Replication of the Novel Human Betacoronavirus EMC on Primary Human Epithelium Highlights Its Zoonotic Potential

Author

Kindler, Eveline, primary, Jónsdóttir, Hulda R., additional, Muth, Doreen, additional, Hamming, Ole J., additional, Hartmann, Rune, additional, Rodriguez, Regulo, additional, Geffers, Robert, additional, Fouchier, Ron A. M., additional, Drosten, Christian, additional, Müller, Marcel A., additional, Dijkman, Ronald, additional, and Thiel, Volker, additional

Published
2013
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39. Viral Shedding and Antibody Response in 37 PatientsWith Middle East Respiratory Syndrome Coronavirus Infection.

Author

Corman, Victor M., Albarrak, Ali M., Omrani, Ali Senosi, Albarrak, Mohammed M., Farah, Mohamed Elamin, Almasri, Malak, Muth, Doreen, Sieberg, Andrea, Meyer, Benjamin, Assiri, Abdullah M., Binger, Tabea, Steinhagen, Katja, Lattwein, Erik, Al-Tawfiq, Jaffar, Müller, Marcel A., Drosten, Christian, and Memish, Ziad A.

Subjects
VIRAL shedding, ANTIBODY formation, MIDDLE East respiratory syndrome, MERS coronavirus, IMMUNOGLOBULIN M, DIAGNOSIS
Abstract

Background. The Middle East respiratory syndrome (MERS) coronavirus causes isolated cases and outbreaks of severe respiratory disease. Essential features of the natural history of disease are poorly understood. Methods. We studied 37 adult patients infected with MERS coronavirus for viral load in the lower and upper respiratory tracts (LRT and URT, respectively), blood, stool, and urine. Antibodies and serum neutralizing activities were determined over the course of disease. Results. One hundred ninety-nine LRT samples collected during the 3 weeks following diagnosis yielded virus RNA in 93% of tests. Average (maximum) viral loads were 5 × 106 (6 × 1010) copies/mL. Viral loads ( positive detection frequencies) in 84 URT samples were 1.9 × 104 copies/mL (47.6%). Thirty-three percent of all 108 serum samples tested yielded viral RNA. Only 14.6% of stool and 2.4% of urine samples yielded viral RNA. All seroconversions occurred during the first 2 weeks after diagnosis, which corresponds to the second and third week after symptom onset. Immunoglobulin M detection provided no advantage in sensitivity over immunoglobulin G (IgG) detection. All surviving patients, but only slightly more than half of all fatal cases, produced IgG and neutralizing antibodies. The levels of IgG and neutralizing antibodies were weakly and inversely correlated with LRT viral loads. Presence of antibodies did not lead to the elimination of virus from LRT. Conclusions. The timing and intensity of respiratory viral shedding in patients with MERS closely matches that of those with severe acute respiratory syndrome. Blood viral RNA does not seem to be infectious. Extrapulmonary loci of virus replication seem possible. Neutralizing antibodies do not suffice to clear the infection. [ABSTRACT FROM AUTHOR]

Published
2016
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40. Human Coronavirus EMC Does Not Require the SARS-Coronavirus Receptor and Maintains Broad Replicative Capability in Mammalian Cell Lines

Author

Müller, Marcel A., primary, Raj, V. Stalin, additional, Muth, Doreen, additional, Meyer, Benjamin, additional, Kallies, Stephan, additional, Smits, Saskia L., additional, Wollny, Robert, additional, Bestebroer, Theo M., additional, Specht, Sabine, additional, Suliman, Tasnim, additional, Zimmermann, Katrin, additional, Binger, Tabea, additional, Eckerle, Isabella, additional, Tschapka, Marco, additional, Zaki, Ali M., additional, Osterhaus, Albert D. M. E., additional, Fouchier, Ron A. M., additional, Haagmans, Bart L., additional, and Drosten, Christian, additional

Published
2012
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41. Genomic Characterization of Severe Acute Respiratory Syndrome-Related Coronavirus in European Bats and Classification of Coronaviruses Based on Partial RNA-Dependent RNA Polymerase Gene Sequences

Author

Drexler, Jan Felix, primary, Gloza-Rausch, Florian, additional, Glende, Jörg, additional, Corman, Victor Max, additional, Muth, Doreen, additional, Goettsche, Matthias, additional, Seebens, Antje, additional, Niedrig, Matthias, additional, Pfefferle, Susanne, additional, Yordanov, Stoian, additional, Zhelyazkov, Lyubomir, additional, Hermanns, Uwe, additional, Vallo, Peter, additional, Lukashev, Alexander, additional, Müller, Marcel Alexander, additional, Deng, Hongkui, additional, Herrler, Georg, additional, and Drosten, Christian, additional

Published
2010
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42. One-step selection of Vaccinia virus-binding DNA aptamers by MonoLEX

Author

Nitsche, Andreas, primary, Kurth, Andreas, additional, Dunkhorst, Anna, additional, Pänke, Oliver, additional, Sielaff, Hendrik, additional, Junge, Wolfgang, additional, Muth, Doreen, additional, Scheller, Frieder, additional, Stöcklein, Walter, additional, Dahmen, Claudia, additional, Pauli, Georg, additional, and Kage, Andreas, additional

Published
2007
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43. Attenuation of replication by a 29 nucleotide deletion in SARS-coronavirus acquired during the early stages of human-to-human transmission

Author

Muth, Doreen, Corman, Victor Max, Roth, Hanna, Binger, Tabea, Dijkman, Ronald, Gottula, Lina Theresa, Gloza-Rausch, Florian, Balboni, Andrea, Battilani, Mara, Rihtarič, Danijela, Toplak, Ivan, Ameneiros, Ramon Seage, Pfeifer, Alexander, Thiel, Volker, Drexler, Jan Felix, Mueller, Marcel Alexander, and Drosten, Christian

Subjects
SARS-coronavirus, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit, 3. Good health
Abstract

A 29 nucleotide deletion in open reading frame 8 (ORF8) is the most obvious genetic change in severe acute respiratory syndrome coronavirus (SARS-CoV) during its emergence in humans. In spite of intense study, it remains unclear whether the deletion actually reflects adaptation to humans. Here we engineered full, partially deleted (-29 nt), and fully deleted ORF8 into a SARS-CoV infectious cDNA clone, strain Frankfurt-1. Replication of the resulting viruses was compared in primate cell cultures as well as Rhinolophus bat cells made permissive for SARS-CoV replication by lentiviral transduction of the human angiotensin-converting enzyme 2 receptor. Cells from cotton rat, goat, and sheep provided control scenarios that represent host systems in which SARS-CoV is neither endemic nor epidemic. Independent of the cell system, the truncation of ORF8 (29 nt deletion) decreased replication up to 23-fold. The effect was independent of the type I interferon response. The 29 nt deletion in SARS-CoV is a deleterious mutation acquired along the initial human-to-human transmission chain. The resulting loss of fitness may be due to a founder effect, which has rarely been documented in processes of viral emergence. These results have important implications for the retrospective assessment of the threat posed by SARS.

44. Efficient replication of the novel human betacoronavirus EMC on primary human epithelium highlights its zoonotic potential

Author

Kindler, Eveline, Jonsdottir, Hulda R., Muth, Doreen, Hamming, Ole J, Hartmann, Rune, Rodriguez, Regulo, Geffers, Robert, Fouchier, Ron A M, Drosten, Christian, Müller, Marcel A, Dijkman, Ronald, and Thiel, Volker

Subjects
630 Agriculture, virus diseases, 3. Good health
Abstract

The recent emergence of a novel human coronavirus (HCoV-EMC) in the Middle East raised considerable concerns, as it is associated with severe acute pneumonia, renal failure, and fatal outcome and thus resembles the clinical presentation of severe acute respiratory syndrome (SARS) observed in 2002 and 2003. Like SARS-CoV, HCoV-EMC is of zoonotic origin and closely related to bat coronaviruses. The human airway epithelium (HAE) represents the entry point and primary target tissue for respiratory viruses and is highly relevant for assessing the zoonotic potential of emerging respiratory viruses, such as HCoV-EMC. Here, we show that pseudostratified HAE cultures derived from different donors are highly permissive to HCoV-EMC infection, and by using reverse transcription (RT)-PCR and RNAseq data, we experimentally determined the identity of seven HCoV-EMC subgenomic mRNAs. Although the HAE cells were readily responsive to type I and type III interferon (IFN), we observed neither a pronounced inflammatory cytokine nor any detectable IFN responses following HCoV-EMC, SARS-CoV, or HCoV-229E infection, suggesting that innate immune evasion mechanisms and putative IFN antagonists of HCoV-EMC are operational in the new host. Importantly, however, we demonstrate that both type I and type III IFN can efficiently reduce HCoV-EMC replication in HAE cultures, providing a possible treatment option in cases of suspected HCoV-EMC infection. IMPORTANCE A novel human coronavirus, HCoV-EMC, has recently been described to be associated with severe respiratory tract infection and fatalities, similar to severe acute respiratory syndrome (SARS) observed during the 2002-2003 epidemic. Closely related coronaviruses replicate in bats, suggesting that, like SARS-CoV, HCoV-EMC is of zoonotic origin. Since the animal reservoir and circumstances of zoonotic transmission are yet elusive, it is critically important to assess potential species barriers of HCoV-EMC infection. An important first barrier against invading respiratory pathogens is the epithelium, representing the entry point and primary target tissue of respiratory viruses. We show that human bronchial epithelia are highly susceptible to HCoV-EMC infection. Furthermore, HCoV-EMC, like other coronaviruses, evades innate immune recognition, reflected by the lack of interferon and minimal inflammatory cytokine expression following infection. Importantly, type I and type III interferon treatment can efficiently reduce HCoV-EMC replication in the human airway epithelium, providing a possible avenue for treatment of emerging virus infections.

45. Mammalian deltavirus without hepadnavirus coinfection in the neotropical rodent Proechimys semispinosus

Author

Fabian Pirzer, Jan Felix Drexler, Christian Drosten, Nora Goldmann, Lina Theresa Gottula, Terry Jones, Doreen Muth, Sofia Paraskevopoulou, Marcel A. Müller, Rachel A. Page, Georg Joachim Eibner, Andrea Rasche, Alexander Christoph Heni, Julian Schmid, Simon Schroeder, Simone Sommer, Dieter Glebe, Victor M. Corman, Paraskevopoulou, Sofia [0000-0003-2608-2596], Pirzer, Fabian [0000-0001-8525-8593], Schmid, Julian [0000-0003-1775-6958], Corman, Victor Max [0000-0002-3605-0136], Gottula, Lina Theresa [0000-0001-5518-3957], Rasche, Andrea [0000-0001-6693-1180], Muth, Doreen [0000-0001-9992-5393], Jones, Terry C [0000-0003-1120-9531], Sommer, Simone [0000-0002-5148-8136], and Apollo - University of Cambridge Repository

Subjects
viruses, Rodentia, Genome, Viral, medicine.disease_cause, Hepadnaviridae, Microbiology, Genome, Virus, neotropical rodent, Rodent Diseases, Cell Line, Tumor, medicine, Animals, Humans, hepadnavirus, Proechimys semispinosus, Phylogeny, Hepatitis B virus, Multidisciplinary, biology, Coinfection, virus diseases, RNA virus, Genomics, biochemical phenomena, metabolism, and nutrition, Biological Sciences, Hepadnaviridae Infections, biology.organism_classification, medicine.disease, Virology, digestive system diseases, Hepatitis D, Satellite virus, Helper virus, Hepadnavirus, Hepatitis Delta Virus, deltavirus
Abstract

Significance Hepatitis delta virus (HDV) aggravates hepatitis B virus (HBV) infection of liver cells. Although the viruses are evolutionarily unrelated, HDV depends on HBV because it requires the HBV envelope protein for its transmission. HDV is only described in humans, which has triggered diverse hypotheses regarding its evolution and origins. Here we show that spiny rats (Proechimys semispinosus) carry a counterpart to HDV that surprisingly does not cause hepatitis and is not linked to HBV. The rodent deltavirus finding alone, but also taken together with the recent deltavirus findings in snakes and other vertebrates and invertebrates, suggests that a deltavirus precursor may have infected mammals before it acquired dependence on HBV as seen in humans., Hepatitis delta virus (HDV) is a human hepatitis-causing RNA virus, unrelated to any other taxonomic group of RNA viruses. Its occurrence as a satellite virus of hepatitis B virus (HBV) is a singular case in animal virology for which no consensus evolutionary explanation exists. Here we present a mammalian deltavirus that does not occur in humans, identified in the neotropical rodent species Proechimys semispinosus. The rodent deltavirus is highly distinct, showing a common ancestor with a recently described deltavirus in snakes. Reverse genetics based on a tandem minus-strand complementary DNA genome copy under the control of a cytomegalovirus (CMV) promoter confirms autonomous genome replication in transfected cells, with initiation of replication from the upstream genome copy. In contrast to HDV, a large delta antigen is not expressed and the farnesylation motif critical for HBV interaction is absent from a genome region that might correspond to a hypothetical rodent large delta antigen. Correspondingly, there is no evidence for coinfection with an HBV-related hepadnavirus based on virus detection and serology in any deltavirus-positive animal. No other coinfecting viruses were detected by RNA sequencing studies of 120 wild-caught animals that could serve as a potential helper virus. The presence of virus in blood and pronounced detection in reproductively active males suggest horizontal transmission linked to competitive behavior. Our study establishes a nonhuman, mammalian deltavirus that occurs as a horizontally transmitted infection, is potentially cleared by immune response, is not focused in the liver, and possibly does not require helper virus coinfection.

Published
2020
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