37 results on '"Hulswit, Ruben J. G."'
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2. Multifunctional human monoclonal antibody combination mediates protection against Rift Valley fever virus at low doses
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Chapman, Nathaniel S., Hulswit, Ruben J. G., Westover, Jonna L. B., Stass, Robert, Paesen, Guido C., Binshtein, Elad, Reidy, Joseph X., Engdahl, Taylor B., Handal, Laura S., Flores, Alejandra, Gowen, Brian B., Bowden, Thomas A., and Crowe, Jr., James E.
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- 2023
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3. Human coronaviruses OC43 and HKU1 bind to 9- O -acetylated sialic acids via a conserved receptor-binding site in spike protein domain A
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Hulswit, Ruben J. G., Lang, Yifei, Bakkers, Mark J. G., Li, Wentao, Li, Zeshi, Schouten, Arie, Ophorst, Bram, van Kuppeveld, Frank J. M., Boons, Geert-Jan, Bosch, Berend-Jan, Huizinga, Eric G., and de Groot, Raoul J.
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- 2019
4. Broad receptor engagement of an emerging global coronavirus may potentiate its diverse cross-species transmissibility
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Li, Wentao, Hulswit, Ruben J. G., Kenney, Scott P., Widjaja, Ivy, Jung, Kwonil, Alhamo, Moyasar A., van Dieren, Brenda, van Kuppeveld, Frank J. M., Saif, Linda J., and Bosch, Berend-Jan
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- 2018
5. Identification of sialic acid-binding function for the Middle East respiratory syndrome coronavirus spike glycoprotein
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Li, Wentao, Hulswit, Ruben J. G., Widjaja, Ivy, Raj, V. Stalin, McBride, Ryan, Peng, Wenjie, Widagdo, W., Tortorici, M. Alejandra, van Dieren, Brenda, Lang, Yifei, van Lent, Jan W. M., Paulson, James C., de Haan, Cornelis A. M., de Groot, Raoul J., van Kuppeveld, Frank J. M., Haagmans, Bart L., and Bosch, Berend-Jan
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- 2017
6. Identification of Evolutionary Trajectories Shared across Human Betacoronaviruses
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Escalera-Zamudio, Marina, primary, Kosakovsky Pond, Sergei L, additional, Martínez de la Viña, Natalia, additional, Gutiérrez, Bernardo, additional, Inward, Rhys P D, additional, Thézé, Julien, additional, van Dorp, Lucy, additional, Castelán-Sánchez, Hugo G, additional, Bowden, Thomas A, additional, Pybus, Oliver G, additional, and Hulswit, Ruben J G, additional
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- 2023
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7. Coronavirus receptor switch explained from the stereochemistry of protein–carbohydrate interactions and a single mutation
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Bakkers, Mark J. G., Zeng, Qinghong, Feitsma, Louris J., Hulswit, Ruben J. G., Li, Zeshi, Westerbeke, Aniek, van Kuppeveld, Frank J. M., Boons, Geert-Jan, Langereis, Martijn A., Huizinga, Eric G., and de Groot, Raoul J.
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- 2016
8. Sialoglycan binding triggers spike opening in a human coronavirus
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Pronker, Matti F, Creutznacher, Robert, Drulyte, Ieva, Hulswit, Ruben J G, Li, Zeshi, van Kuppeveld, Frank J M, Snijder, Joost, Lang, Yifei, Bosch, Berend-Jan, Boons, Geert-Jan, Frank, Martin, de Groot, Raoul J, Hurdiss, Daniel L, Pronker, Matti F, Creutznacher, Robert, Drulyte, Ieva, Hulswit, Ruben J G, Li, Zeshi, van Kuppeveld, Frank J M, Snijder, Joost, Lang, Yifei, Bosch, Berend-Jan, Boons, Geert-Jan, Frank, Martin, de Groot, Raoul J, and Hurdiss, Daniel L
- Abstract
Coronavirus spike proteins mediate receptor binding and membrane fusion, making them prime targets for neutralizing antibodies. In the cases of severe acute respiratory syndrome coronavirus, severe acute respiratory syndrome coronavirus 2 and Middle East respiratory syndrome coronavirus, spike proteins transition freely between open and closed conformations to balance host cell attachment and immune evasion 1-5. Spike opening exposes domain S1 B, allowing it to bind to proteinaceous receptors 6,7, and is also thought to enable protein refolding during membrane fusion 4,5. However, with a single exception, the pre-fusion spike proteins of all other coronaviruses studied so far have been observed exclusively in the closed state. This raises the possibility of regulation, with spike proteins more commonly transitioning to open states in response to specific cues, rather than spontaneously. Here, using cryogenic electron microscopy and molecular dynamics simulations, we show that the spike protein of the common cold human coronavirus HKU1 undergoes local and long-range conformational changes after binding a sialoglycan-based primary receptor to domain S1 A. This binding triggers the transition of S1 B domains to the open state through allosteric interdomain crosstalk. Our findings provide detailed insight into coronavirus attachment, with possibilities of dual receptor usage and priming of entry as a means of immune escape.
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- 2023
9. Identification of Evolutionary Trajectories Shared across Human Betacoronaviruses
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Escalera-Zamudio, Marina, Kosakovsky Pond, Sergei L, Martínez de la Viña, Natalia, Gutiérrez, Bernardo, Inward, Rhys P D, Thézé, Julien, van Dorp, Lucy, Castelán-Sánchez, Hugo G, Bowden, Thomas A, Pybus, Oliver G, Hulswit, Ruben J G, Escalera-Zamudio, Marina, Kosakovsky Pond, Sergei L, Martínez de la Viña, Natalia, Gutiérrez, Bernardo, Inward, Rhys P D, Thézé, Julien, van Dorp, Lucy, Castelán-Sánchez, Hugo G, Bowden, Thomas A, Pybus, Oliver G, and Hulswit, Ruben J G
- Abstract
Comparing the evolution of distantly related viruses can provide insights into common adaptive processes related to shared ecological niches. Phylogenetic approaches, coupled with other molecular evolution tools, can help identify mutations informative on adaptation, although the structural contextualization of these to functional sites of proteins may help gain insight into their biological properties. Two zoonotic betacoronaviruses capable of sustained human-to-human transmission have caused pandemics in recent times (SARS-CoV-1 and SARS-CoV-2), although a third virus (MERS-CoV) is responsible for sporadic outbreaks linked to animal infections. Moreover, two other betacoronaviruses have circulated endemically in humans for decades (HKU1 and OC43). To search for evidence of adaptive convergence between established and emerging betacoronaviruses capable of sustained human-to-human transmission (HKU1, OC43, SARS-CoV-1, and SARS-CoV-2), we developed a methodological pipeline to classify shared nonsynonymous mutations as putatively denoting homoplasy (repeated mutations that do not share direct common ancestry) or stepwise evolution (sequential mutations leading towards a novel genotype). In parallel, we look for evidence of positive selection and draw upon protein structure data to identify potential biological implications. We find 30 candidate mutations, from which 4 (codon sites 18121 [nsp14/residue 28], 21623 [spike/21], 21635 [spike/25], and 23948 [spike/796]; SARS-CoV-2 genome numbering) further display evolution under positive selection and proximity to functional protein regions. Our findings shed light on potential mechanisms underlying betacoronavirus adaptation to the human host and pinpoint common mutational pathways that may occur during establishment of human endemicity.
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- 2023
10. Sialoglycan binding triggers spike opening in a human coronavirus
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Sub Biomol.Mass Spectrometry & Proteom., Virologie, Afd Chemical Biology and Drug Discovery, Sub Chemical Biology and Drug Discovery, Infectious Diseases and Immunology - Virology, Pronker, Matti F, Creutznacher, Robert, Drulyte, Ieva, Hulswit, Ruben J G, Li, Zeshi, van Kuppeveld, Frank J M, Snijder, Joost, Lang, Yifei, Bosch, Berend-Jan, Boons, Geert-Jan, Frank, Martin, de Groot, Raoul J, Hurdiss, Daniel L, Sub Biomol.Mass Spectrometry & Proteom., Virologie, Afd Chemical Biology and Drug Discovery, Sub Chemical Biology and Drug Discovery, Infectious Diseases and Immunology - Virology, Pronker, Matti F, Creutznacher, Robert, Drulyte, Ieva, Hulswit, Ruben J G, Li, Zeshi, van Kuppeveld, Frank J M, Snijder, Joost, Lang, Yifei, Bosch, Berend-Jan, Boons, Geert-Jan, Frank, Martin, de Groot, Raoul J, and Hurdiss, Daniel L
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- 2023
11. Identification of Evolutionary Trajectories Shared across Human Betacoronaviruses
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Virologie, Infectious Diseases and Immunology - Virology, Escalera-Zamudio, Marina, Kosakovsky Pond, Sergei L, Martínez de la Viña, Natalia, Gutiérrez, Bernardo, Inward, Rhys P D, Thézé, Julien, van Dorp, Lucy, Castelán-Sánchez, Hugo G, Bowden, Thomas A, Pybus, Oliver G, Hulswit, Ruben J G, Virologie, Infectious Diseases and Immunology - Virology, Escalera-Zamudio, Marina, Kosakovsky Pond, Sergei L, Martínez de la Viña, Natalia, Gutiérrez, Bernardo, Inward, Rhys P D, Thézé, Julien, van Dorp, Lucy, Castelán-Sánchez, Hugo G, Bowden, Thomas A, Pybus, Oliver G, and Hulswit, Ruben J G
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- 2023
12. Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil
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Faria, Nuno R., primary, Mellan, Thomas A., additional, Whittaker, Charles, additional, Claro, Ingra M., additional, Candido, Darlan da S., additional, Mishra, Swapnil, additional, Crispim, Myuki A. E., additional, Sales, Flavia C. S., additional, Hawryluk, Iwona, additional, McCrone, John T., additional, Hulswit, Ruben J. G., additional, Franco, Lucas A. M., additional, Ramundo, Mariana S., additional, de Jesus, Jaqueline G., additional, Andrade, Pamela S., additional, Coletti, Thais M., additional, Ferreira, Giulia M., additional, Silva, Camila A. M., additional, Manuli, Erika R., additional, Pereira, Rafael H. M., additional, Peixoto, Pedro S., additional, Kraemer, Moritz U. G., additional, Gaburo, Nelson, additional, Camilo, Cecilia da C., additional, Hoeltgebaum, Henrique, additional, Souza, William M., additional, Rocha, Esmenia C., additional, de Souza, Leandro M., additional, de Pinho, Mariana C., additional, Araujo, Leonardo J. T., additional, Malta, Frederico S. V., additional, de Lima, Aline B., additional, Silva, Joice do P., additional, Zauli, Danielle A. G., additional, Ferreira, Alessandro C. de S., additional, Schnekenberg, Ricardo P., additional, Laydon, Daniel J., additional, Walker, Patrick G. T., additional, Schlüter, Hannah M., additional, dos Santos, Ana L. P., additional, Vidal, Maria S., additional, Del Caro, Valentina S., additional, Filho, Rosinaldo M. F., additional, dos Santos, Helem M., additional, Aguiar, Renato S., additional, Proença-Modena, José L., additional, Nelson, Bruce, additional, Hay, James A., additional, Monod, Mélodie, additional, Miscouridou, Xenia, additional, Coupland, Helen, additional, Sonabend, Raphael, additional, Vollmer, Michaela, additional, Gandy, Axel, additional, Prete, Carlos A., additional, Nascimento, Vitor H., additional, Suchard, Marc A., additional, Bowden, Thomas A., additional, Pond, Sergei L. K., additional, Wu, Chieh-Hsi, additional, Ratmann, Oliver, additional, Ferguson, Neil M., additional, Dye, Christopher, additional, Loman, Nick J., additional, Lemey, Philippe, additional, Rambaut, Andrew, additional, Fraiji, Nelson A., additional, Carvalho, Maria do P. S. S., additional, Pybus, Oliver G., additional, Flaxman, Seth, additional, Bhatt, Samir, additional, and Sabino, Ester C., additional
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- 2021
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13. Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil
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Faria, Nuno R., Mellan, Thomas A., Whittaker, Charles, Claro, Ingra M., Candido, Darlan da S., Mishra, Swapnil, Crispim, Myuki A. E., Sales, Flavia C., Hawryluk, Iwona, McCrone, John T., Hulswit, Ruben J. G., Franco, Lucas A. M., Ramundo, Mariana S., de Jesus, Jaqueline G., Andrade, Pamela S., Coletti, Thais M., Ferreira, Giulia M., Silva, Camila A. M., Manuli, Erika R., Pereira, Rafael H. M., Peixoto, Pedro S., Kraemer, Moritz U., Gaburo, Nelson, Camilo, Cecilia da C., Hoeltgebaum, Henrique, Souza, William M., Rocha, Esmenia C., de Souza, Leandro M., de Pinho, Mariana C., Araujo, Leonardo J. T., Malta, Frederico S., de Lima, Aline B., Silva, Joice do P., Zauli, Danielle A. G., Ferreira, Alessandro C. de S., Schnekenberg, Ricardo P., Laydon, Daniel J., Walker, Patrick G. T., Schlueter, Hannah M., dos Santos, Ana L. P., Vidal, Maria S., Del Caro, Valentina S., Filho, Rosinaldo M. F., dos Santos, Helem M., Aguiar, Renato S., Proenca-Modena, Jose L. P., Nelson, Bruce, Hay, James A., Monod, Melodie, Miscouridou, Xenia, Coupland, Helen, Sonabend, Raphael, Vollmer, Michaela, Gandy, Axel, Prete, Carlos A., Nascimento, Vitor H., Suchard, Marc A., Bowden, Thomas A., Pond, Sergei L. K., Wu, Chieh-Hsi, Ratmann, Oliver, Ferguson, Neil M., Dye, Christopher, Loman, Nick J., Lemey, Philippe, Rambaut, Andrew, Fraiji, Nelson A., Carvalho, Maria do P. S. S., Pybus, Oliver G., Flaxman, Seth, Bhatt, Samir, Sabino, Ester C., Faria, Nuno R., Mellan, Thomas A., Whittaker, Charles, Claro, Ingra M., Candido, Darlan da S., Mishra, Swapnil, Crispim, Myuki A. E., Sales, Flavia C., Hawryluk, Iwona, McCrone, John T., Hulswit, Ruben J. G., Franco, Lucas A. M., Ramundo, Mariana S., de Jesus, Jaqueline G., Andrade, Pamela S., Coletti, Thais M., Ferreira, Giulia M., Silva, Camila A. M., Manuli, Erika R., Pereira, Rafael H. M., Peixoto, Pedro S., Kraemer, Moritz U., Gaburo, Nelson, Camilo, Cecilia da C., Hoeltgebaum, Henrique, Souza, William M., Rocha, Esmenia C., de Souza, Leandro M., de Pinho, Mariana C., Araujo, Leonardo J. T., Malta, Frederico S., de Lima, Aline B., Silva, Joice do P., Zauli, Danielle A. G., Ferreira, Alessandro C. de S., Schnekenberg, Ricardo P., Laydon, Daniel J., Walker, Patrick G. T., Schlueter, Hannah M., dos Santos, Ana L. P., Vidal, Maria S., Del Caro, Valentina S., Filho, Rosinaldo M. F., dos Santos, Helem M., Aguiar, Renato S., Proenca-Modena, Jose L. P., Nelson, Bruce, Hay, James A., Monod, Melodie, Miscouridou, Xenia, Coupland, Helen, Sonabend, Raphael, Vollmer, Michaela, Gandy, Axel, Prete, Carlos A., Nascimento, Vitor H., Suchard, Marc A., Bowden, Thomas A., Pond, Sergei L. K., Wu, Chieh-Hsi, Ratmann, Oliver, Ferguson, Neil M., Dye, Christopher, Loman, Nick J., Lemey, Philippe, Rambaut, Andrew, Fraiji, Nelson A., Carvalho, Maria do P. S. S., Pybus, Oliver G., Flaxman, Seth, Bhatt, Samir, and Sabino, Ester C.
- Abstract
Cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Manaus, Brazil, resurged in late 2020 despite previously high levels of infection. Genome sequencing of viruses sampled in Manaus between November 2020 and January 2021 revealed the emergence and circulation of a novel SARS-CoV-2 variant of concern. Lineage P.1 acquired 17 mutations, including a trio in the spike protein (K417T, E484K, and N501Y) associated with increased binding to the human ACE2 (angiotensin-converting enzyme 2) receptor. Molecular clock analysis shows that P.1 emergence occurred around mid-November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.7- to 2.4-fold more transmissible and that previous (non-P.1) infection provides 54 to 79% of the protection against infection with P.1 that it provides against non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness.
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- 2021
14. Antibody evasion by the Brazilian P.1 strain of SARS-CoV-2
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Dejnirattisai, Wanwisa, primary, Zhou, Daming, additional, Supasa, Piyada, additional, Liu, Chang, additional, Mentzer, Alexander J., additional, Ginn, Helen M., additional, Zhao, Yuguang, additional, Duyvesteyn, Helen M.E., additional, Tuekprakhon, Aekkachai, additional, Nutalai, Rungtiwa, additional, Wang, Beibei, additional, Paesen, Guido C., additional, López-Camacho, César, additional, Slon-Campos, Jose, additional, Walter, Thomas S., additional, Skelly, Donal, additional, Clemens, Sue Ann Costa, additional, Naveca, Felipe Gomes, additional, Nascimento, Valdinete, additional, Nascimento, Fernanda, additional, da Costa, Cristiano Fernandes, additional, Resende, Paola C., additional, Pauvolid-Correa, Alex, additional, Siqueira, Marilda M., additional, Dold, Christina, additional, Levin, Robert, additional, Dong, Tao, additional, Pollard, Andrew J., additional, Knight, Julian C., additional, Crook, Derrick, additional, Lambe, Teresa, additional, Clutterbuck, Elizabeth, additional, Bibi, Sagida, additional, Flaxman, Amy, additional, Bittaye, Mustapha, additional, Belij-Rammerstorfer, Sandra, additional, Gilbert, Sarah, additional, Carroll, Miles W., additional, Klenerman, Paul, additional, Barnes, Eleanor, additional, Dunachie, Susanna J., additional, Paterson, Neil G., additional, Williams, Mark A., additional, Hall, David R., additional, Hulswit, Ruben J. G., additional, Bowden, Thomas A., additional, Fry, Elizabeth E., additional, Mongkolsapaya, Juthathip, additional, Ren, Jingshan, additional, Stuart, David I., additional, and Screaton, Gavin R., additional
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- 2021
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15. Genomics and epidemiology of a novel SARS-CoV-2 lineage in Manaus, Brazil
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Faria, Nuno R., primary, Mellan, Thomas A., additional, Whittaker, Charles, additional, Claro, Ingra M., additional, Candido, Darlan da S., additional, Mishra, Swapnil, additional, Crispim, Myuki A. E., additional, Sales, Flavia C., additional, Hawryluk, Iwona, additional, McCrone, John T., additional, Hulswit, Ruben J. G., additional, Franco, Lucas A. M., additional, Ramundo, Mariana S., additional, de Jesus, Jaqueline G., additional, Andrade, Pamela S., additional, Coletti, Thais M., additional, Ferreira, Giulia M., additional, Silva, Camila A. M., additional, Manuli, Erika R., additional, Pereira, Rafael H. M., additional, Peixoto, Pedro S., additional, Kraemer, Moritz U., additional, Gaburo, Nelson, additional, Camilo, Cecilia da C., additional, Hoeltgebaum, Henrique, additional, Souza, William M., additional, Rocha, Esmenia C., additional, de Souza, Leandro M., additional, de Pinho, Mariana C., additional, Araujo, Leonardo J. T, additional, Malta, Frederico S. V., additional, de Lima, Aline B., additional, Silva, Joice do P., additional, Zauli, Danielle A. G., additional, Ferreira, Alessandro C. de S., additional, Schnekenberg, Ricardo P, additional, Laydon, Daniel J., additional, Walker, Patrick G. T., additional, Schlüter, Hannah M., additional, dos Santos, Ana L. P., additional, Vidal, Maria S., additional, Del Caro, Valentina S., additional, Filho, Rosinaldo M. F., additional, dos Santos, Helem M., additional, Aguiar, Renato S., additional, Modena, José L. P., additional, Nelson, Bruce, additional, Hay, James A., additional, Monod, Melodie, additional, Miscouridou, Xenia, additional, Coupland, Helen, additional, Sonabend, Raphael, additional, Vollmer, Michaela, additional, Gandy, Axel, additional, Suchard, Marc A., additional, Bowden, Thomas A., additional, Pond, Sergei L. K., additional, Wu, Chieh-Hsi, additional, Ratmann, Oliver, additional, Ferguson, Neil M., additional, Dye, Christopher, additional, Loman, Nick J., additional, Lemey, Philippe, additional, Rambaut, Andrew, additional, Fraiji, Nelson A., additional, Carvalho, Maria do P. S. S., additional, Pybus, Oliver G., additional, Flaxman, Seth, additional, Bhatt, Samir, additional, and Sabino, Ester C., additional
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- 2021
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16. Recent Advances in Bunyavirus Glycoprotein Research: Precursor Processing, Receptor Binding and Structure
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Hulswit, Ruben J. G., primary, Paesen, Guido C., additional, Bowden, Thomas A., additional, and Shi, Xiaohong, additional
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- 2021
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17. Identification of Common Deletions in the Spike Protein of Severe Acute Respiratory Syndrome Coronavirus 2
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Liu, Zhe, primary, Zheng, Huanying, additional, Lin, Huifang, additional, Li, Mingyue, additional, Yuan, Runyu, additional, Peng, Jinju, additional, Xiong, Qianling, additional, Sun, Jiufeng, additional, Li, Baisheng, additional, Wu, Jie, additional, Yi, Lina, additional, Peng, Xiaofang, additional, Zhang, Huan, additional, Zhang, Wei, additional, Hulswit, Ruben J. G., additional, Loman, Nick, additional, Rambaut, Andrew, additional, Ke, Changwen, additional, Bowden, Thomas A., additional, Pybus, Oliver G., additional, and Lu, Jing, additional
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- 2020
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18. Molecular rationale for antibody-mediated targeting of the hantavirus fusion glycoprotein
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Rissanen, Ilona, Stass, Robert, Krumm, Stefanie A., Seow, Jeffrey, Hulswit, Ruben J. G., Paesen, Guido C., Hepojoki, Jussi, Vapalahti, Olli, Lundkvist, Åke, Reynard, Olivier, Volchkov, Viktor, Doores, Katie J., Huiskonen, Juha T., Bowden, Thomas A., Rissanen, Ilona, Stass, Robert, Krumm, Stefanie A., Seow, Jeffrey, Hulswit, Ruben J. G., Paesen, Guido C., Hepojoki, Jussi, Vapalahti, Olli, Lundkvist, Åke, Reynard, Olivier, Volchkov, Viktor, Doores, Katie J., Huiskonen, Juha T., and Bowden, Thomas A.
- Abstract
The intricate lattice of Gn and Gc glycoprotein spike complexes on the hantavirus envelope facilitates host-cell entry and is the primary target of the neutralizing antibody-mediated immune response. Through study of a neutralizing monoclonal antibody termed mAb P-4G2, which neutralizes the zoonotic pathogen Puumala virus (PUUV), we provide a molecular-level basis for antibody-mediated targeting of the hantaviral glycoprotein lattice. Crystallographic analysis demonstrates that P-4G2 binds to a multi-domain site on PUUV Gc and may preclude fusogenic rearrangements of the glycoprotein that are required for host-cell entry. Furthermore, cryoelectron microscopy of PUUV-like particles in the presence of P-4G2 reveals a lattice-independent configuration of the Gc, demonstrating that P-4G2 perturbs the (Gn-Gc)(4) lattice. This work provides a structure-based blueprint for rationalizing antibody-mediated targeting of hantaviruses.
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- 2020
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19. Complexity and Diversity of the Mammalian Sialome Revealed by Nidovirus Virolectins
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Langereis, Martijn A, Bakkers, Mark J G, Deng, Lingquan, Padler-Karavani, Vered, Vervoort, Stephin J, Hulswit, Ruben J G, van Vliet, Arno L W, Gerwig, Gerrit J, de Poot, Stefanie A H, Boot, Willemijn, van Ederen, Anne Marie, Heesters, Balthasar A, van der Loos, Chris M, van Kuppeveld, Frank J M, Yu, Hai, Huizinga, Eric G, Chen, Xi, Varki, Ajit, Kamerling, Johannis P, de Groot, Raoul J, Bio organic Chemistry, Crystal and Structural Chemistry, dI&I I&I-1, LS Virologie, Sub Membrane Biochemistry & Biophysics, Afd Chemical Biology and Drug Discovery, Sub Crystal and Structural Chemistry, Bio organic Chemistry, Crystal and Structural Chemistry, dI&I I&I-1, LS Virologie, Sub Membrane Biochemistry & Biophysics, Afd Chemical Biology and Drug Discovery, and Sub Crystal and Structural Chemistry
- Subjects
Medical Physiology ,Nidovirales ,Biochemistry ,Genome ,Viral ,Non-U.S. Gov't ,lcsh:QH301-705.5 ,Mammals ,Regulation of gene expression ,0303 health sciences ,biology ,Research Support, Non-U.S. Gov't ,030302 biochemistry & molecular biology ,Acetylation ,Lipids ,3. Good health ,Cell biology ,Hemagglutinins ,Sialome ,Glycan ,1.1 Normal biological development and functioning ,Hemagglutinins, Viral ,Research Support ,Article ,General Biochemistry, Genetics and Molecular Biology ,N.I.H ,03 medical and health sciences ,Species Specificity ,Research Support, N.I.H., Extramural ,Underpinning research ,Journal Article ,Animals ,Humans ,Differential expression ,030304 developmental biology ,Biochemistry, Genetics and Molecular Biology(all) ,Cell growth ,Proteins ,Extramural ,N-Acetylneuraminic Acid ,lcsh:Biology (General) ,Gene Expression Regulation ,Sialic Acids ,biology.protein ,Acetylesterase ,Generic health relevance ,Biochemistry and Cell Biology ,Viral Fusion Proteins ,Function (biology) ,Genetics and Molecular Biology(all) - Abstract
SUMMARY Sialic acids (Sias), 9-carbon-backbone sugars, are among the most complex and versatile molecules of life. As terminal residues of glycans on proteins and lipids, Sias are key elements of glycotopes of both cellular and microbial lectins and thus act as important molecular tags in cell recognition and signaling events. Their functions in such interactions can be regulated by post-synthetic modifications, the most common of which is differential Sia-O-acetylation (O-Ac-Sias). The biology of O-Ac-Sias remains mostly unexplored, largely because of limitations associated with their specific in situ detection. Here, we show that dual-function hemagglutinin-esterase envelope proteins of nidoviruses distinguish between a variety of closely related O-Ac-Sias. By using soluble forms of hemagglutinin-esterases as lectins and sialate-O-acetylesterases, we demonstrate differential expression of distinct O-Ac-sialoglycan populations in an organ-, tissue- and cell-specific fashion. Our findings indicate that programmed Sia-O-acetylation/de-O-acetylation may be critical to key aspects of cell development, homeostasis, and/or function., Graphical Abstract
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- 2015
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20. Human coronaviruses OC43 and HKU1 bind to 9-O-acetylated sialic acids via a conserved receptor-binding site in spike protein domain A
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LS Virologie, dI&I I&I-1, Sub Crystal and Structural Chemistry, Sub Chemical Biology and Drug Discovery, Afd Chemical Biology and Drug Discovery, Chemical Biology and Drug Discovery, Hulswit, Ruben J G, Lang, Yifei, Bakkers, Mark J G, Li, Wentao, Li, Zeshi, Schouten, Arie, Ophorst, Bram, van Kuppeveld, Frank J M, Boons, Geert-Jan, Bosch, Berend-Jan, Huizinga, Eric G, de Groot, Raoul J, LS Virologie, dI&I I&I-1, Sub Crystal and Structural Chemistry, Sub Chemical Biology and Drug Discovery, Afd Chemical Biology and Drug Discovery, Chemical Biology and Drug Discovery, Hulswit, Ruben J G, Lang, Yifei, Bakkers, Mark J G, Li, Wentao, Li, Zeshi, Schouten, Arie, Ophorst, Bram, van Kuppeveld, Frank J M, Boons, Geert-Jan, Bosch, Berend-Jan, Huizinga, Eric G, and de Groot, Raoul J
- Published
- 2019
21. Human coronaviruses OC43 and HKU1 bind to 9-O-acetylated sialic acids via a conserved receptor-binding site in spike protein domain A
- Author
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Chemical Biology and Drug Discovery, LS Virologie, dI&I I&I-1, Afd Chemical Biology and Drug Discovery, Sub Crystal and Structural Chemistry, Sub Chemical Biology and Drug Discovery, Hulswit, Ruben J G, Lang, Yifei, Bakkers, Mark J G, Li, Wentao, Li, Zeshi, Schouten, Arie, Ophorst, Bram, van Kuppeveld, Frank J M, Boons, Geert-Jan, Bosch, Berend-Jan, Huizinga, Eric G, de Groot, Raoul J, Chemical Biology and Drug Discovery, LS Virologie, dI&I I&I-1, Afd Chemical Biology and Drug Discovery, Sub Crystal and Structural Chemistry, Sub Chemical Biology and Drug Discovery, Hulswit, Ruben J G, Lang, Yifei, Bakkers, Mark J G, Li, Wentao, Li, Zeshi, Schouten, Arie, Ophorst, Bram, van Kuppeveld, Frank J M, Boons, Geert-Jan, Bosch, Berend-Jan, Huizinga, Eric G, and de Groot, Raoul J
- Published
- 2019
22. Broad receptor engagement of an emerging global coronavirus may potentiate its diverse cross-species transmissibility
- Author
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dI&I I&I-1, LS Virologie, Li, Wentao, Hulswit, Ruben J G, Kenney, Scott P, Widjaja, Ivy, Jung, Kwonil, Alhamo, Moyasar A, van Dieren, Brenda, van Kuppeveld, Frank J M, Saif, Linda J, Bosch, Berend-Jan, dI&I I&I-1, LS Virologie, Li, Wentao, Hulswit, Ruben J G, Kenney, Scott P, Widjaja, Ivy, Jung, Kwonil, Alhamo, Moyasar A, van Dieren, Brenda, van Kuppeveld, Frank J M, Saif, Linda J, and Bosch, Berend-Jan
- Published
- 2018
23. Identification of sialic acid-binding function for the Middle East respiratory syndrome coronavirus spike glycoprotein
- Author
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dI&I I&I-1, LS Virologie, Li, Wentao, Hulswit, Ruben J G, Widjaja, Ivy, Raj, V Stalin, McBride, Ryan, Peng, Wenjie, Widagdo, W, Tortorici, M Alejandra, van Dieren, Brenda, Lang, Yifei, van Lent, Jan W M, Paulson, James C, de Haan, Cornelis A M, de Groot, Raoul J, van Kuppeveld, Frank J M, Haagmans, Bart L, Bosch, Berend-Jan, dI&I I&I-1, LS Virologie, Li, Wentao, Hulswit, Ruben J G, Widjaja, Ivy, Raj, V Stalin, McBride, Ryan, Peng, Wenjie, Widagdo, W, Tortorici, M Alejandra, van Dieren, Brenda, Lang, Yifei, van Lent, Jan W M, Paulson, James C, de Haan, Cornelis A M, de Groot, Raoul J, van Kuppeveld, Frank J M, Haagmans, Bart L, and Bosch, Berend-Jan
- Published
- 2017
24. Betacoronavirus Adaptation to Humans Involved Progressive Loss of Hemagglutinin-Esterase Lectin Activity
- Author
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dI&I I&I-1, LS Virologie, Bakkers, Mark J G, Lang, Yifei, Feitsma, Louris J, Hulswit, Ruben J G, de Poot, Stefanie A H, van Vliet, Arno L W, Margine, Irina, de Groot-Mijnes, Jolanda D F, van Kuppeveld, Frank J M, Langereis, Martijn A, Huizinga, Eric G, de Groot, Raoul J, dI&I I&I-1, LS Virologie, Bakkers, Mark J G, Lang, Yifei, Feitsma, Louris J, Hulswit, Ruben J G, de Poot, Stefanie A H, van Vliet, Arno L W, Margine, Irina, de Groot-Mijnes, Jolanda D F, van Kuppeveld, Frank J M, Langereis, Martijn A, Huizinga, Eric G, and de Groot, Raoul J
- Published
- 2017
25. Betacoronavirus Adaptation to Humans Involved Progressive Loss of Hemagglutinin-Esterase Lectin Activity
- Author
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Bakkers, Mark J G, Lang, Yifei, Feitsma, Louris J, Hulswit, Ruben J G, de Poot, Stefanie A H, van Vliet, Arno L W, Margine, Irina, de Groot-Mijnes, Jolanda D F, van Kuppeveld, Frank J M, Langereis, Martijn A, Huizinga, Eric G, de Groot, Raoul J, dI&I I&I-1, LS Virologie, dI&I I&I-1, and LS Virologie
- Subjects
0301 basic medicine ,Viral protein ,viruses ,Adaptation, Biological ,Hemagglutinins, Viral ,Virus Attachment ,Host tropism ,medicine.disease_cause ,Microbiology ,Article ,Coronavirus OC43, Human ,03 medical and health sciences ,chemistry.chemical_compound ,Lectins ,Virology ,medicine ,Influenza A virus ,Animals ,Humans ,Receptor ,biology ,Hemagglutinin esterase ,Lectin ,biology.organism_classification ,Sialic acid ,030104 developmental biology ,chemistry ,Mutation ,biology.protein ,Receptors, Virus ,Parasitology ,Viral Fusion Proteins ,Betacoronavirus ,Protein Binding - Abstract
Summary Human beta1-coronavirus (β1CoV) OC43 emerged relatively recently through a single zoonotic introduction. Like related animal β1CoVs, OC43 uses 9-O-acetylated sialic acid as receptor determinant. β1CoV receptor binding is typically controlled by attachment/fusion spike protein S and receptor-binding/receptor-destroying hemagglutinin-esterase protein HE. We show that following OC43’s introduction into humans, HE-mediated receptor binding was selected against and ultimately lost through progressive accumulation of mutations in the HE lectin domain. Consequently, virion-associated receptor-destroying activity toward multivalent glycoconjugates was reduced and altered such that some clustered receptor populations are no longer cleaved. Loss of HE lectin function was also observed for another respiratory human coronavirus, HKU1. This thus appears to be an adaptation to the sialoglycome of the human respiratory tract and for replication in human airways. The findings suggest that the dynamics of virion-glycan interactions contribute to host tropism. Our observations are relevant also to other human respiratory viruses of zoonotic origin, particularly influenza A virus., Graphical Abstract, Highlights • Adaption of coronaviruses OC43 and HKU1 to humans involved loss of HE lectin function • OC43 HE receptor binding site was lost via progressive accumulation of mutations • Loss of HE receptor binding alters sialate-9-O-acetylesterase receptor destroying activity • Balance of receptor binding and receptor destruction contributes to host tropism, Coronavirus OC43 entered the human population relatively recently. Bakkers et al. report that as an adaptation to replication in human airways, the OC43 hemagglutinin-esterase lost its receptor-binding function. Consequently, virion-associated receptor-destroying activity toward clustered sialoglycan-based receptor determinants was reduced. Suggestive of convergent evolution, human respiratory coronavirus HKU1 underwent similar changes.
- Published
- 2017
26. Coronavirus receptor switch explained from the stereochemistry of protein-carbohydrate interactions and a single mutation
- Author
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Bakkers, Mark J G, Zeng, Qinghong, Feitsma, Louris J, Hulswit, Ruben J G, Li, Zeshi, Westerbeke, Aniek, van Kuppeveld, Frank J M, Boons, Geert-Jan, Langereis, Martijn A, Huizinga, Eric G, de Groot, Raoul J, Bakkers, Mark J G, Zeng, Qinghong, Feitsma, Louris J, Hulswit, Ruben J G, Li, Zeshi, Westerbeke, Aniek, van Kuppeveld, Frank J M, Boons, Geert-Jan, Langereis, Martijn A, Huizinga, Eric G, and de Groot, Raoul J
- Abstract
Hemagglutinin-esterases (HEs) are bimodular envelope proteins of orthomyxoviruses, toroviruses, and coronaviruses with a carbohydrate-binding "lectin" domain appended to a receptor-destroying sialate-O-acetylesterase ("esterase"). In concert, these domains facilitate dynamic virion attachment to cell-surface sialoglycans. Most HEs (type I) target 9-O-acetylated sialic acids (9-O-Ac-Sias), but one group of coronaviruses switched to using 4-O-Ac-Sias instead (type II). This specificity shift required quasisynchronous adaptations in the Sia-binding sites of both lectin and esterase domains. Previously, a partially disordered crystal structure of a type II HE revealed how the shift in lectin ligand specificity was achieved. How the switch in esterase substrate specificity was realized remained unresolved, however. Here, we present a complete structure of a type II HE with a receptor analog in the catalytic site and identify the mutations underlying the 9-O- to 4-O-Ac-Sia substrate switch. We show that (i) common principles pertaining to the stereochemistry of protein-carbohydrate interactions were at the core of the transition in lectin ligand and esterase substrate specificity; (ii) in consequence, the switch in O-Ac-Sia specificity could be readily accomplished via convergent intramolecular coevolution with only modest architectural changes in lectin and esterase domains; and (iii) a single, inconspicuous Ala-to-Ser substitution in the catalytic site was key to the emergence of the type II HEs. Our findings provide fundamental insights into how proteins "see" sugars and how this affects protein and virus evolution.
- Published
- 2016
27. Coronavirus receptor switch explained from the stereochemistry of protein-carbohydrate interactions and a single mutation
- Author
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dI&I I&I-1, LS Virologie, Sub Crystal and Structural Chemistry, Sub Chemical pharmacology, Sub Algemeen Scheikunde, Medicinal Chemistry and Chemical Biology, Bakkers, Mark J G, Zeng, Qinghong, Feitsma, Louris J, Hulswit, Ruben J G, Li, Zeshi, Westerbeke, Aniek, van Kuppeveld, Frank J M, Boons, Geert-Jan, Langereis, Martijn A, Huizinga, Eric G, de Groot, Raoul J, dI&I I&I-1, LS Virologie, Sub Crystal and Structural Chemistry, Sub Chemical pharmacology, Sub Algemeen Scheikunde, Medicinal Chemistry and Chemical Biology, Bakkers, Mark J G, Zeng, Qinghong, Feitsma, Louris J, Hulswit, Ruben J G, Li, Zeshi, Westerbeke, Aniek, van Kuppeveld, Frank J M, Boons, Geert-Jan, Langereis, Martijn A, Huizinga, Eric G, and de Groot, Raoul J
- Published
- 2016
28. Broad receptor engagement of an emerging global coronavirus may potentiate its diverse cross-species transmissibility.
- Author
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Wentao Li, Hulswit, Ruben J. G., Ivy Widjaja, van Dieren, Brenda, van Kuppeveld, Frank J. M., Bosch, Berend-Jan, Kenney, Scott P., Kwonil Jung, Alhamo, Moyasar A., and Saif, Linda J.
- Subjects
PORCINE epidemic diarrhea virus ,CORONAVIRUS diseases ,TRANSMISSIBLE gastroenteritis in swine ,ANTIGEN receptors ,GLYCOPROTEINS - Abstract
Porcine deltacoronavirus (PDCoV), identified in 2012, is a common enteropathogen of swine with worldwide distribution. The source and evolutionary history of this virus is, however, unknown. PDCoV belongs to the Deltacoronavirus genus that comprises predominantly avian CoV. Phylogenetic analysis suggests that PDCoV originated relatively recently from a host-switching event between birds and mammals. Insight into receptor engagement by PDCoV may shed light into such an exceptional phenomenon. Here we report that PDCoV employs host aminopeptidase N (APN) as an entry receptor and interacts with APN via domain B of its spike (S) protein. Infection of porcine cells with PDCoV was drastically reduced by APN knockout and rescued after reconstitution of APN expression. In addition, we observed that PDCoV efficiently infects cells of unusual broad species range, including human and chicken. Accordingly, PDCoV S was found to target the phylogenetically conserved catalytic domain of APN. Moreover, transient expression of porcine, feline, human, and chicken APN renders cells susceptible to PDCoV infection. Binding of PDCoV to an interspecies conserved site on APN may facilitate direct transmission of PDCoV to nonreservoir species, including humans, potentially reflecting the mechanism that enabled a virus, ancestral to PDCoV, to breach the species barrier between birds and mammals. The APN cell surface protein is also used by several members of the Alphacoronavirus genus. Hence, our data constitute the second identification of CoVs from different genera that use the same receptor, implying that CoV receptor selection is subjected to specific restrictions that are still poorly understood. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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29. Complexity and Diversity of the Mammalian Sialome Revealed by Nidovirus Virolectins
- Author
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Langereis, Martijn A., Bakkers, Mark J G, Deng, Lingquan, Padler-Karavani, Vered, Vervoort, Stephin J., Hulswit, Ruben J G, van Vliet, Arno L W, Gerwig, Gerrit J., de Poot, Stefanie A H, Boot, Willemijn, van Ederen, Anne Marie, Heesters, Balthasar A., van der Loos, Chris M., van Kuppeveld, Frank J M, Yu, Hai, Huizinga, Eric G., Chen, Xi, Varki, Ajit, Kamerling, Johannis P., de Groot, Raoul J., Langereis, Martijn A., Bakkers, Mark J G, Deng, Lingquan, Padler-Karavani, Vered, Vervoort, Stephin J., Hulswit, Ruben J G, van Vliet, Arno L W, Gerwig, Gerrit J., de Poot, Stefanie A H, Boot, Willemijn, van Ederen, Anne Marie, Heesters, Balthasar A., van der Loos, Chris M., van Kuppeveld, Frank J M, Yu, Hai, Huizinga, Eric G., Chen, Xi, Varki, Ajit, Kamerling, Johannis P., and de Groot, Raoul J.
- Published
- 2015
30. Complexity and Diversity of the Mammalian Sialome Revealed by Nidovirus Virolectins
- Author
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Bio organic Chemistry, Crystal and Structural Chemistry, dI&I I&I-1, LS Virologie, Sub Membrane Biochemistry & Biophysics, Afd Chemical Biology and Drug Discovery, Sub Crystal and Structural Chemistry, Langereis, Martijn A, Bakkers, Mark J G, Deng, Lingquan, Padler-Karavani, Vered, Vervoort, Stephin J, Hulswit, Ruben J G, van Vliet, Arno L W, Gerwig, Gerrit J, de Poot, Stefanie A H, Boot, Willemijn, van Ederen, Anne Marie, Heesters, Balthasar A, van der Loos, Chris M, van Kuppeveld, Frank J M, Yu, Hai, Huizinga, Eric G, Chen, Xi, Varki, Ajit, Kamerling, Johannis P, de Groot, Raoul J, Bio organic Chemistry, Crystal and Structural Chemistry, dI&I I&I-1, LS Virologie, Sub Membrane Biochemistry & Biophysics, Afd Chemical Biology and Drug Discovery, Sub Crystal and Structural Chemistry, Langereis, Martijn A, Bakkers, Mark J G, Deng, Lingquan, Padler-Karavani, Vered, Vervoort, Stephin J, Hulswit, Ruben J G, van Vliet, Arno L W, Gerwig, Gerrit J, de Poot, Stefanie A H, Boot, Willemijn, van Ederen, Anne Marie, Heesters, Balthasar A, van der Loos, Chris M, van Kuppeveld, Frank J M, Yu, Hai, Huizinga, Eric G, Chen, Xi, Varki, Ajit, Kamerling, Johannis P, and de Groot, Raoul J
- Published
- 2015
31. Complexity and Diversity of the Mammalian Sialome Revealed by Nidovirus Virolectins
- Author
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CMM Groep Coffer, Orthopaedie Onderzoek, MMB, Langereis, Martijn A., Bakkers, Mark J G, Deng, Lingquan, Padler-Karavani, Vered, Vervoort, Stephin J., Hulswit, Ruben J G, van Vliet, Arno L W, Gerwig, Gerrit J., de Poot, Stefanie A H, Boot, Willemijn, van Ederen, Anne Marie, Heesters, Balthasar A., van der Loos, Chris M., van Kuppeveld, Frank J M, Yu, Hai, Huizinga, Eric G., Chen, Xi, Varki, Ajit, Kamerling, Johannis P., de Groot, Raoul J., CMM Groep Coffer, Orthopaedie Onderzoek, MMB, Langereis, Martijn A., Bakkers, Mark J G, Deng, Lingquan, Padler-Karavani, Vered, Vervoort, Stephin J., Hulswit, Ruben J G, van Vliet, Arno L W, Gerwig, Gerrit J., de Poot, Stefanie A H, Boot, Willemijn, van Ederen, Anne Marie, Heesters, Balthasar A., van der Loos, Chris M., van Kuppeveld, Frank J M, Yu, Hai, Huizinga, Eric G., Chen, Xi, Varki, Ajit, Kamerling, Johannis P., and de Groot, Raoul J.
- Published
- 2015
32. Identification of sialic acid-binding function for the Middle East respiratory syndrome coronavirus spike glycoprotein.
- Author
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Wentao Li, Hulswit, Ruben J. G., Widjaja, Ivy, Raj, V. Stalin, Mcbride, Ryan, Wenjie Peng, Widagdo, W., Tortorici, M. Alejandra, Van Dieren, Brenda, Yifei Lang, Van Lent, Jan W. M., Paulson, James C., De Haan, Cornelis A. M., De Groot, Raoul J., Van Kuppeveld, Frank J. M., Haagmans, Bart L., and Bosch, Berend-Jan
- Subjects
SIALIC acids ,MIDDLE East respiratory syndrome ,GLYCOPROTEIN analysis ,CD26 antigen ,NEURAMINIDASE ,DIAGNOSIS ,THERAPEUTICS - Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) targets the epithelial cells of the respiratory tract both in humans and in its natural host, the dromedary camel. Virion attachment to host cells is mediated by 20-nm-long homotrimers of spike envelope protein S. The N-terminal subunit of each S protomer, called S1, folds into four distinct domains designated S1
A through S1D . Binding of MERS-CoV to the cell surface entry receptor dipeptidyl peptidase 4 (DPP4) occurs via S1B . We now demonstrate that in addition to DPP4, MERS-CoV binds to sialic acid (Sia). Initially demonstrated by hemagglutination assay with human erythrocytes and intact virus, MERS-CoV Sia-binding activity was assigned to S subdomain S1A . When multivalently displayed on nanoparticles, S1 or S1A bound to human erythrocytes and to human mucin in a strictly Sia-dependent fashion. Glycan array analysis revealed a preference for α2,3-linked Sias over α2,6-linked Sias, which correlates with the differential distribution of α2,3-linked Sias and the predominant sites of MERS-CoV replication in the upper and lower respiratory tracts of camels and humans, respectively. Binding is hampered by Sia modifications such as 5-N-glycolylation and (7,)9-O-acetylation. Depletion of cell surface Sia by neuraminidase treatment inhibited MERS-CoV entry of Calu-3 human airway cells, thus providing direct evidence that virus-Sia interactions may aid in virion attachment. The combined observations lead us to propose that high-specificity, low-affinity attachment of MERS-CoV to sialoglycans during the preattachment or early attachment phase may form another determinant governing the host range and tissue tropism of this zoonotic pathogen. [ABSTRACT FROM AUTHOR]- Published
- 2017
- Full Text
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33. Identification of Common Deletions in the Spike Protein of Severe Acute Respiratory Syndrome Coronavirus 2.
- Author
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Zhe Liu, Huanying Zheng, Huifang Lin, Mingyue Li, Runyu Yuan, Jinju Peng, Qianling Xiong, Jiufeng Sun, Baisheng Li, Jie Wu, Lina Yi, Xiaofang Peng, Huan Zhang, Wei Zhang, Hulswit, Ruben J. G., Loman, Nick, Rambaut, Andrew, Changwen Ke, Bowden, Thomas A., and Pybus, Oliver G.
- Subjects
- *
COVID-19 , *SARS-CoV-2 , *VIRAL genomes - Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus first identified in December 2019. Notable features that make SARS-CoV-2 distinct from most other previously identified betacoronaviruses include a receptor binding domain and a unique insertion of 12 nucleotides or 4 amino acids (PRRA) at the S1/S2 boundary. In this study, we identified two deletion variants of SARS-CoV-2 that either directly affect the polybasic cleavage site itself (NSPRRAR) or a flanking sequence (QTQTN). These deletions were verified by multiple sequencing methods. In vitro results showed that the deletion of NSPRRAR likely does not affect virus replication in Vero and Vero-E6 cells; however, the deletion of QTQTN may restrict late-phase viral replication. The deletion of QTQTN was detected in 3 of 68 clinical samples and 12 of 24 in vitro-isolated viruses, while the deletion of NSPRRAR was identified in 3 in vitro-isolated viruses. Our data indicate that (i) there may be distinct selection pressures on SARS-CoV-2 replication or infection in vitro and in vivo; (ii) an efficient mechanism for deleting this region from the viral genome may exist, given that the deletion variant is commonly detected after two rounds of cell passage; and (iii) the PRRA insertion, which is unique to SARS-CoV-2, is not fixed during virus replication in vitro. These findings provide information to aid further investigation of SARS-CoV-2 infection mechanisms and a better understanding of the NSPRRAR deletion variant observed here. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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34. Identification of evolutionary trajectories shared across human betacoronaviruses.
- Author
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Escalera-Zamudio M, Kosakovsky Pond SL, de la Viña NM, Gutiérrez B, Inward RPD, Thézé J, van Dorp L, Castelán-Sánchez HG, Bowden TA, Pybus OG, and Hulswit RJG
- Abstract
Comparing the evolution of distantly related viruses can provide insights into common adaptive processes related to shared ecological niches. Phylogenetic approaches, coupled with other molecular evolution tools, can help identify mutations informative on adaptation, whilst the structural contextualization of these to functional sites of proteins may help gain insight into their biological properties. Two zoonotic betacoronaviruses capable of sustained human-to-human transmission have caused pandemics in recent times (SARS-CoV-1 and SARS-CoV-2), whilst a third virus (MERS-CoV) is responsible for sporadic outbreaks linked to animal infections. Moreover, two other betacoronaviruses have circulated endemically in humans for decades (HKU1 and OC43). To search for evidence of adaptive convergence between established and emerging betacoronaviruses capable of sustained human-to-human transmission (HKU1, OC43, SARS-CoV-1 and SARS-CoV-2), we developed a methodological pipeline to classify shared non-synonymous mutations as putatively denoting homoplasy (repeated mutations that do not share direct common ancestry) or stepwise evolution (sequential mutations leading towards a novel genotype). In parallel, we look for evidence of positive selection, and draw upon protein structure data to identify potential biological implications. We find 30 mutations, with four of these [codon sites 18121 (nsp14/residue 28), 21623 (spike/21), 21635 (spike/25) and 23948 (spike/796); SARS-CoV-2 genome numbering] displaying evolution under positive selection and proximity to functional protein regions. Our findings shed light on potential mechanisms underlying betacoronavirus adaptation to the human host and pinpoint common mutational pathways that may occur during establishment of human endemicity.
- Published
- 2023
- Full Text
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35. Antibody evasion by the P.1 strain of SARS-CoV-2.
- Author
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Dejnirattisai W, Zhou D, Supasa P, Liu C, Mentzer AJ, Ginn HM, Zhao Y, Duyvesteyn HME, Tuekprakhon A, Nutalai R, Wang B, López-Camacho C, Slon-Campos J, Walter TS, Skelly D, Costa Clemens SA, Naveca FG, Nascimento V, Nascimento F, Fernandes da Costa C, Resende PC, Pauvolid-Correa A, Siqueira MM, Dold C, Levin R, Dong T, Pollard AJ, Knight JC, Crook D, Lambe T, Clutterbuck E, Bibi S, Flaxman A, Bittaye M, Belij-Rammerstorfer S, Gilbert SC, Carroll MW, Klenerman P, Barnes E, Dunachie SJ, Paterson NG, Williams MA, Hall DR, Hulswit RJG, Bowden TA, Fry EE, Mongkolsapaya J, Ren J, Stuart DI, and Screaton GR
- Subjects
- Binding Sites, COVID-19 therapy, COVID-19 virology, Cell Line, Humans, Immune Evasion, Immunization, Passive, Mutation, Protein Binding, Protein Domains, SARS-CoV-2 genetics, Sequence Deletion, Spike Glycoprotein, Coronavirus chemistry, Spike Glycoprotein, Coronavirus genetics, Vaccination, Vaccines immunology, COVID-19 Serotherapy, Antibodies, Monoclonal immunology, Antibodies, Neutralizing immunology, Antibodies, Viral immunology, COVID-19 immunology, SARS-CoV-2 immunology, Spike Glycoprotein, Coronavirus immunology
- Abstract
Terminating the SARS-CoV-2 pandemic relies upon pan-global vaccination. Current vaccines elicit neutralizing antibody responses to the virus spike derived from early isolates. However, new strains have emerged with multiple mutations, including P.1 from Brazil, B.1.351 from South Africa, and B.1.1.7 from the UK (12, 10, and 9 changes in the spike, respectively). All have mutations in the ACE2 binding site, with P.1 and B.1.351 having a virtually identical triplet (E484K, K417N/T, and N501Y), which we show confer similar increased affinity for ACE2. We show that, surprisingly, P.1 is significantly less resistant to naturally acquired or vaccine-induced antibody responses than B.1.351, suggesting that changes outside the receptor-binding domain (RBD) impact neutralization. Monoclonal antibody (mAb) 222 neutralizes all three variants despite interacting with two of the ACE2-binding site mutations. We explain this through structural analysis and use the 222 light chain to largely restore neutralization potency to a major class of public antibodies., Competing Interests: Declaration of interests G.R.S. sits on the GSK Vaccines Scientific Advisory Board. Oxford University holds intellectual property related to the Oxford-AstraZeneca vaccine. A.J.P. is chair of the UK Department Health and Social Care’s (DHSC) Joint Committee on Vaccination & Immunisation (JCVI) but does not participate in the JCVI COVID-19 committee and is a member of the World Health Organization’s (WHO’s) SAGE. The views expressed in this article do not necessarily represent the views of DHSC, JCVI, or WHO. S.C.G. is co-founder of Vaccitech (collaborators in the early development of this vaccine candidate) and is named as an inventor on a patent covering use of ChAdOx1-vectored vaccines and a patent application covering this SARS-CoV-2 vaccine (PCT/GB2012/000467). T.L. is named as an inventor on a patent application covering this SARS-CoV-2 vaccine and was a consultant to Vaccitech for an unrelated project during the conduct of the study. The University of Oxford has entered into a partnership with AstraZeneca on coronavirus vaccine development.The University of Oxford has protected intellectual property disclosed in this publication., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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- View/download PDF
36. Genomics and epidemiology of a novel SARS-CoV-2 lineage in Manaus, Brazil.
- Author
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Faria NR, Mellan TA, Whittaker C, Claro IM, Candido DDS, Mishra S, Crispim MAE, Sales FC, Hawryluk I, McCrone JT, Hulswit RJG, Franco LAM, Ramundo MS, de Jesus JG, Andrade PS, Coletti TM, Ferreira GM, Silva CAM, Manuli ER, Pereira RHM, Peixoto PS, Kraemer MU, Gaburo N Jr, Camilo CDC, Hoeltgebaum H, Souza WM, Rocha EC, de Souza LM, de Pinho MC, Araujo LJT, Malta FSV, de Lima AB, Silva JDP, Zauli DAG, de S Ferreira AC, Schnekenberg RP, Laydon DJ, Walker PGT, Schlüter HM, Dos Santos ALP, Vidal MS, Del Caro VS, Filho RMF, Dos Santos HM, Aguiar RS, Modena JLP, Nelson B, Hay JA, Monod M, Miscouridou X, Coupland H, Sonabend R, Vollmer M, Gandy A, Suchard MA, Bowden TA, Pond SLK, Wu CH, Ratmann O, Ferguson NM, Dye C, Loman NJ, Lemey P, Rambaut A, Fraiji NA, Carvalho MDPSS, Pybus OG, Flaxman S, Bhatt S, and Sabino EC
- Abstract
Cases of SARS-CoV-2 infection in Manaus, Brazil, resurged in late 2020, despite high levels of previous infection there. Through genome sequencing of viruses sampled in Manaus between November 2020 and January 2021, we identified the emergence and circulation of a novel SARS-CoV-2 variant of concern, lineage P.1, that acquired 17 mutations, including a trio in the spike protein (K417T, E484K and N501Y) associated with increased binding to the human ACE2 receptor. Molecular clock analysis shows that P.1 emergence occurred around early November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.4-2.2 times more transmissible and 25-61% more likely to evade protective immunity elicited by previous infection with non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness., Competing Interests: Competing interests: Authors declare that they have no competing interests.
- Published
- 2021
- Full Text
- View/download PDF
37. Naturally Acquired Rift Valley Fever Virus Neutralizing Antibodies Predominantly Target the Gn Glycoprotein.
- Author
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Wright D, Allen ER, Clark MHA, Gitonga JN, Karanja HK, Hulswit RJG, Taylor I, Biswas S, Marshall J, Mwololo D, Muriuki J, Bett B, Bowden TA, and Warimwe GM
- Abstract
Rift Valley fever (RVF) is a viral hemorrhagic disease first discovered in Kenya in 1930. Numerous animal studies have demonstrated that protective immunity is acquired following RVF virus (RVFV) infection and that this correlates with acquisition of virus-neutralizing antibodies (nAbs) that target the viral envelope glycoproteins. However, naturally acquired immunity to RVF in humans is poorly described. Here, we characterized the immune response to the viral envelope glycoproteins, Gn and Gc, in RVFV-exposed Kenyan adults. Long-lived IgG (dominated by IgG1 subclass) and T cell responses were detected against both Gn and Gc. However, antigen-specific antibody depletion experiments showed that Gn-specific antibodies dominate the RVFV nAb response. IgG avidity against Gn, but not Gc, correlated with nAb titers. These data are consistent with the greater level of immune accessibility of Gn on the viral envelope surface and confirm the importance of Gn as an integral component for RVF vaccine development., Competing Interests: The authors declare no competing interests., (© 2020 The Author(s).)
- Published
- 2020
- Full Text
- View/download PDF
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