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4 results on '"Alonzi, Dominic S."'

1. The role and uses of antibodies in COVID-19 infections: a living review

Author

Scourfield, D Oliver, Reed, Sophie G, Quastel, Max, Alderson, Jennifer, Bart, Valentina M T, Teijeira Crespo, Alicia, Jones, Ruth, Pring, Ellie, Richter, Felix Clemens, Ahern, David J, Almuttaqi, Hannah, Alonzi, Dominic S, Alrubayyi, Aljawharah, Alsaleh, Ghada, Batchelor, Vicky, Bayliss, Rebecca, Berthold, Dorothée L, Bezbradica, Jelena S, Bharuchq, Tehmina, Borrmann, Helene, Borsa, Mariana, Borst, Rowie, Brun, Juliane, Burnell, Stephanie E A, Capitani, Lorenzo, Cavounidis, Athena, Chapman, Lucy, Chauveau, Anne, Cifuentes, Liliana, Codd, Amy Susan, Compeer, Ewoud Bernardus, Coveney, Clarissa, Cross, Amy, Danielli, Sara, Davies, Luke C, Dendrou, Calliope A, Dimonte, Sandra, Peter Durairaj, Ruban Rex, Dustin, Lynn B, Dyer, Arthur, Fielding, Ceri, Fischer, Fabian, Gallimore, Awen, Galloway, Sarah, Gammage, Anís, Gea-Mallorquí, Ester, Godkin, Andrew, Hanna, Stephanie Jean, Heuberger, Cornelia, Hulin-Curtis, Sarah, Issa, Fadi, Jones, Emma, Ladell, Kristin, Lauder, Sarah N, Liddiard, Kate, Ligoxygakis, Petros, Lu, Fangfang, MacLachlan, Bruce, Maleki-Toyserkani, Shayda, Mann, Elizabeth H, Marzeda, Anna M, James Matthews, Reginald, Mazet, Julie M, Milicic, Anita, Mitchell, Emma, Moon, Owen, Nguyen, Van Dien, OHanlon, Miriam, Eléonore Pavillet, Clara, Peppa, Dimitra, Pires, Ana, Pring, Eleanor, Reed, Sophie, Rehwinkel, Jan, Richmond, Niamh, Robinson, Alice J B, Rodrigues, Patrícia R S, Sabberwal, Pragati, Sami, Arvind, Peres, Raphael Sanches, Sattentau, Quentin, Schonfeldova, Barbora, Scourfield, David Oliver, Selvakumar, Tharini A, Shepherd, Freya R, Shorten, Cariad, Simon, Anna Katharina, Smith, Adrian L, Crespo, Alicia Teijeira, Tellier, Michael, Thornton, Emily, Uhl, Lion F K, van Grinsven, Erinke, Wann, Angus K T, Williams, Richard, Wilson, Joseph D, Zhou, Dingxi, Zhu, Zihan, and Consortium, Oxford-Cardiff COVID-19 Literature

Subjects
0301 basic medicine, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Review Article, Disease, 03 medical and health sciences, 0302 clinical medicine, Immunity, Pandemic, antibodies, Medicine, Infection control, biology, SARS-CoV-2, business.industry, COVID-19, General Medicine, vaccines, nanobodies, 030104 developmental biology, convalescent plasma, Immunology, biology.protein, AcademicSubjects/SCI00960, Antibody, business, long-term immunity, 030217 neurology & neurosurgery
Abstract

Coronavirus disease 2019 has generated a rapidly evolving field of research, with the global scientific community striving for solutions to the current pandemic. Characterizing humoral responses towards SARS-CoV-2, as well as closely related strains, will help determine whether antibodies are central to infection control, and aid the design of therapeutics and vaccine candidates. This review outlines the major aspects of SARS-CoV-2-specific antibody research to date, with a focus on the various prophylactic and therapeutic uses of antibodies to alleviate disease in addition to the potential of cross-reactive therapies and the implications of long-term immunity.

Published
2021

2. Mucosal immune responses in COVID19 - a living review

Author

Pearson, Claire F, Jeffery, Rebecca, Ahern, David J, Almuttaqi, Hannah, Alonzi, Dominic S, Alrubayyi, Aljawharah, Alsaleh, Ghada, Bart, Valentina M T, Batchelor, Vicky, Bayliss, Rebecca, Berthold, Dorothée L, Bezbradica, Jelena S, Bharuchq, Tehmina, Borrmann, Helene, Borsa, Mariana, Borst, Rowie, Brun, Juliane, Burnell, Stephanie, Capitani, Lorenzo, Cavounidis, Athena, Chapman, Lucy, Chauveau, Anne, Cifuentes, Liliana, Codd, Amy Susan, Compeer, Ewoud Bernardus, Coveney, Clarissa, Cross, Amy, Danielli, Sara, Davies, Luke C, Dendrou, Calliope A, Dimonte, Sandra, Peter Durairaj, Ruban Rex, Dustin, Lynn B, Dyer, Arthur, Fielding, Ceri, Fischer, Fabian, Gallimore, Awen, Galloway, Sarah, Gammage, Anís, Gea-Mallorquí, Ester, Godkin, Andrew, Hanna, Stephanie Jean, Heuberger, Cornelia, Hulin-Curtis, Sarah, Issa, Fadi, Jones, Emma, Jones, Ruth, Ladell, Kristin, Lauder, Sarah N, Liddiard, Kate, Ligoxygakis, Petros, Lu, Fangfang, MacLachlan, Bruce, Maleki-Toyserkani, Shayda, Mann, Elizabeth H, Marzeda, Anna M, Matthews, Reginald James, Mazet, Julie M, Milicic, Anita, Mitchell, Emma, Moon, Owen, Nguyen, Van Dien, OHanlon, Miriam, Pavillet, Clara Eléonore, Peppa, Dimitra, Pires, Ana, Pring, Eleanor, Quastel, Max, Reed, Sophie, Rehwinkel, Jan, Richmond, Niamh, Richter, Felix Clemens, Robinson, Alice J B, Rodrigues, Patrícia R S, Sabberwal, Pragati, Sami, Arvind, Peres, Raphael Sanches, Sattentau, Quentin, Schonfeldova, Barbora, Scourfield, David Oliver, Selvakumar, Tharini A, Shepherd, Freya R, Shorten, Cariad, Simon, Anna Katharina, Smith, Adrian L, Crespo, Alicia Teijeira, Tellier, Michael, Thornton, Emily, Uhl, Lion F K, van Grinsven, Erinke, Wann, Angus K T, Williams, Richard, Wilson, Joseph D, Zhou, Dingxi, Zhu, Zihan, and Thornton, Emily E

Subjects
0301 basic medicine, Gastrointestinal tract, Mucosal Immune Responses, Lung, Coronavirus disease 2019 (COVID-19), business.industry, Short Communication, COVID-19, microbiome, General Medicine, Disease, Virus, lung, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Immune system, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Immunology, medicine, mucosal immunity, gut, Microbiome, business
Abstract

COVID-19 was initially characterized as a disease primarily of the lungs, but it is becoming increasingly clear that the SARS-CoV2 virus is able to infect many organs and cause a broad pathological response. The primary infection site is likely to be a mucosal surface, mainly the lungs or the intestine, where epithelial cells can be infected with virus. Although it is clear that virus within the lungs can cause severe pathology, driven by an exaggerated immune response, infection within the intestine generally seems to cause minor or no symptoms. In this review, we compare the disease processes between the lungs and gastrointestinal tract, and what might drive these different responses. As the microbiome is a key part of mucosal barrier sites, we also consider the effect that microbial species may play on infection and the subsequent immune responses. Because of difficulties obtaining tissue samples, there are currently few studies focused on the local mucosal response rather than the systemic response, but understanding the local immune response will become increasingly important for understanding the mechanisms of disease in order to develop better treatments.

Published
2020

3. T cell phenotypes in COVID-19 - a living review

Author

Hanna, Stephanie J, Codd, Amy S, Gea-Mallorqui, Ester, Scourfield, D Oliver, Richter, Felix C, Ladell, Kristin, Borsa, Mariana, Compeer, Ewoud B, Moon, Owen R, Galloway, Sarah A E, Dimonte, Sandra, Capitani, Lorenzo, Shepherd, Freya R, Wilson, Joseph D, Uhl, Lion F K, Ahern, David J, Almuttaqi, Hannah, Alonzi, Dominic S, Alrubayyi, Aljawharah, Alsaleh, Ghada, Bart, Valentina M T, Batchelor, Vicky, Bayliss, Rebecca, Berthold, Dorothée L, Bezbradica, Jelena S, Bharuchq, Tehmina, Borrmann, Helene, Borst, Rowie, Brun, Juliane, Burnell, Stephanie, Cavounidis, Athena, Chapman, Lucy, Chauveau, Anne, Cifuentes, Liliana, Codd, Amy Susan, Compeer, Ewoud Bernardus, Coveney, Clarissa, Cross, Amy, Danielli, Sara, Davies, Luke C, Dendrou, Calliope A, Peter Durairaj, Ruban Rex, Dustin, Lynn B, Dyer, Arthur, Fielding, Ceri, Fischer, Fabian, Gallimore, Awen, Galloway, Sarah, Gammage, Anís, Gea-Mallorquí, Ester, Godkin, Andrew, Heuberger, Cornelia, Hulin-Curtis, Sarah, Issa, Fadi, Jones, Emma, Jones, Ruth, Lauder, Sarah N, Liddiard, Kate, Ligoxygakis, Petros, Lu, Fangfang, MacLachlan, Bruce, Maleki-Toyserkani, Shayda, Mann, Elizabeth H, Marzeda, Anna M, Matthews, Reginald James, Mazet, Julie M, Milicic, Anita, Mitchell, Emma, Moon, Owen, Nguyen, Van Dien, OHanlon, Miriam, Eléonore Pavillet, Clara, Peppa, Dimitra, Pires, Ana, Pring, Eleanor, Quastel, Max, Reed, Sophie, Rehwinkel, Jan, Richmond, Niamh, Richter, Felix Clemens, Robinson, Alice J B, Rodrigues, Patrícia R S, Sabberwal, Pragati, Sami, Arvind, Peres, Raphael Sanches, Sattentau, Quentin, Schonfeldova, Barbora, Scourfield, David Oliver, Selvakumar, Tharini A, Shorten, Cariad, Simon, Anna Katharina, Smith, Adrian L, Crespo, Alicia Teijeira, Tellier, Michael, Thornton, Emily, van Grinsven, Erinke, Wann, Angus K T, Williams, Richard, Zhou, Dingxi, Zhu, Zihan, Gallimore, Awen M, and Consortium, Oxford-Cardiff COVID-19 Literature

Subjects
0301 basic medicine, T cell, Short Communication, T cells, Biology, phenotypes, COVID-19, antigen-specific, peripheral blood, lung, Virus, 03 medical and health sciences, 0302 clinical medicine, Immune system, medicine, Lung, Mechanism (biology), General Medicine, Acquired immune system, Phenotype, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Immunology, AcademicSubjects/SCI00960, Function (biology)
Abstract

COVID-19 is characterized by profound lymphopenia in the peripheral blood, and the remaining T cells display altered phenotypes, characterized by a spectrum of activation and exhaustion. However, antigen-specific T cell responses are emerging as a crucial mechanism for both clearance of the virus and as the most likely route to long-lasting immune memory that would protect against re-infection. Therefore, T cell responses are also of considerable interest in vaccine development. Furthermore, persistent alterations in T cell subset composition and function post-infection have important implications for patients’ long-term immune function. In this review, we examine T cell phenotypes, including those of innate T cells, in both peripheral blood and lungs, and consider how key markers of activation and exhaustion correlate with, and may be able to predict, disease severity. We focus on SARS-CoV-2-specific T cells to elucidate markers that may indicate formation of antigen-specific T cell memory. We also examine peripheral T cell phenotypes in recovery and the likelihood of long-lasting immune disruption. Finally, we discuss T cell phenotypes in the lung as important drivers of both virus clearance and tissue damage. As our knowledge of the adaptive immune response to COVID-19 rapidly evolves, it has become clear that while some areas of the T cell response have been investigated in some detail, others, such as the T cell response in children remain largely unexplored. Therefore, this review will also highlight areas where T cell phenotypes require urgent characterisation.

Published
2020

4. Clamping, bending, and twisting inter-domain motions in the misfold-recognising portion of UDP-glucose:glycoprotein glucosyl-transferase

Author

Modenutti, Carlos P., Blanco Capurro, Juan I., Ibba, Roberta, Vasiljević, Snežana, Hensen, Mario, Alonzi, Dominic S., Chandran, Anu V., Hill, Johan C., Rushton, Jonathan, Kumar, Abhinav, Rubichi, Simone, Lia, Andrea, Tax, Gábor, Marti, Lucia, Santino, Angelo, Martí, Marcelo A., Zitzmann, Nicole, and Roversi, Pietro

Abstract

SummaryUDP-glucose:glycoprotein glucosyltransferase (UGGT) is the only known glycoprotein folding quality control checkpoint in the eukaryotic glycoprotein secretory pathway. When the enzyme detects a misfolded glycoprotein in the Endoplasmic Reticulum (ER), it dispatches it for ER retention by re-glucosylating it on one of its N-linked glycans. Recent crystal structures of a fungal UGGT have suggested the enzyme is conformationally mobile. Here, a negative stain electron microscopy reconstruction of UGGT in complex with a monoclonal antibody confirms that the misfold-sensing N-terminal portion of UGGT and its C-terminal catalytic domain are tightly associated. Molecular Dynamics (MD) simulations capture UGGT in so far unobserved conformational states, giving new insights into the molecule’s flexibility. Principal component analysis of the MD trajectories affords a description of UGGT’s overall inter-domain motions, highlighting three types of inter-domain movements: bending, twisting and clamping. These inter-domain motions modify the accessible surface area of the enzyme’s central saddle, likely enabling the protein to recognize and re-glucosylate substrates of different sizes and shapes, and/or re-glucosylate N-linked glycans situated at variable distances from the site of misfold. We propose to name “Parodi limit” the maximum distance between a site of misfolding on a UGGT glycoprotein substrate and an N-linked glycan that monomeric UGGT can re-glucosylate on the same glycoprotein. MD simulations estimate the Parodi limit to be around 60-70 Å. Re-glucosylation assays using UGGT deletion mutants suggest that the TRXL2 domain is necessary for activity against urea-misfolded bovine thyroglobulin. Taken together, our findings support a “one-size-fits-all adjustable spanner” substrate recognition model, with a crucial role for the TRXL2 domain in the recruitment of misfolded substrates to the enzyme’s active site.

Published
2019

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