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2. SARS-CoV-2 evolution during treatment of chronic infection

Author

Baker, Stephen, Dougan, Gordon, Hess, Christoph, Kingston, Nathalie, Lehner, Paul J, Lyons, Paul A, Matheson, Nicholas J, Owehand, Willem H, Saunders, Caroline, Summers, Charlotte, Thaventhiran, James ED, Toshner, Mark, Weekes, Michael P, Bucke, Ashlea, Calder, Jo, Canna, Laura, Domingo, Jason, Elmer, Anne, Fuller, Stewart, Harris, Julie, Hewitt, Sarah, Kennet, Jane, Jose, Sherly, Kourampa, Jenny, Meadows, Anne, O’Brien, Criona, Price, Jane, Publico, Cherry, Rastall, Rebecca, Ribeiro, Carla, Rowlands, Jane, Ruffolo, Valentina, Tordesillas, Hugo, Bullman, Ben, Dunmore, Benjamin J, Fawke, Stuart, Gräf, Stefan, Hodgson, Josh, Huang, Christopher, Hunter, Kelvin, Jones, Emma, Legchenko, Ekaterina, Matara, Cecilia, Martin, Jennifer, Mescia, Federica, O’Donnell, Ciara, Pointon, Linda, Pond, Nicole, Shih, Joy, Sutcliffe, Rachel, Tilly, Tobias, Treacy, Carmen, Tong, Zhen, Wood, Jennifer, Wylot, Marta, Bergamaschi, Laura, Betancourt, Ariana, Bower, Georgie, Cossetti, Chiara, De Sa, Aloka, Epping, Madeline, Gleadall, Nick, Grenfell, Richard, Hinch, Andrew, Huhn, Oisin, Jackson, Sarah, Jarvis, Isobel, Lewis, Daniel, Marsden, Joe, Nice, Francesca, Okecha, Georgina, Omarjee, Ommar, Perera, Marianne, Richoz, Nathan, Romashova, Veronika, Yarkoni, Natalia Savinykh, Sharma, Rahul, Stefanucci, Luca, Stephens, Jonathan, Strezlecki, Mateusz, Turner, Lori, De Bie, Eckart MDD, Bunclark, Katherine, Josipovic, Masa, Mackay, Michael, Rossi, Sabrina, Selvan, Mayurun, Spencer, Sarah, Yong, Cissy, Ansaripour, Ali, Michael, Alice, Mwaura, Lucy, Patterson, Caroline, Polwarth, Gary, Polgarova, Petra, di Stefano, Giovanni, Fahey, Codie, Michel, Rachel, and Bong, Sze-How

Subjects
Immunization, Pneumonia & Influenza, Lung, Prevention, Genetics, Vaccine Related, Biotechnology, Pneumonia, Emerging Infectious Diseases, Biodefense, Infectious Diseases, 2.1 Biological and endogenous factors, Aetiology, Infection, Good Health and Well Being, Adenosine Monophosphate, Aged, Alanine, Antibodies, Neutralizing, Antibodies, Viral, COVID-19, Chronic Disease, Evolution, Molecular, Genome, Viral, High-Throughput Nucleotide Sequencing, Humans, Immune Evasion, Immune Tolerance, Immunization, Passive, Immunosuppression Therapy, Male, Mutagenesis, Mutant Proteins, Mutation, Phylogeny, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Time Factors, Viral Load, Virus Shedding, COVID-19 Drug Treatment, COVID-19 Serotherapy, CITIID-NIHR BioResource COVID-19 Collaboration, COVID-19 Genomics UK (COG-UK) Consortium, General Science & Technology
Abstract

The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for virus infection through the engagement of the human ACE2 protein1 and is a major antibody target. Here we show that chronic infection with SARS-CoV-2 leads to viral evolution and reduced sensitivity to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma, by generating whole-genome ultra-deep sequences for 23 time points that span 101 days and using in vitro techniques to characterize the mutations revealed by sequencing. There was little change in the overall structure of the viral population after two courses of remdesivir during the first 57 days. However, after convalescent plasma therapy, we observed large, dynamic shifts in the viral population, with the emergence of a dominant viral strain that contained a substitution (D796H) in the S2 subunit and a deletion (ΔH69/ΔV70) in the S1 N-terminal domain of the spike protein. As passively transferred serum antibodies diminished, viruses with the escape genotype were reduced in frequency, before returning during a final, unsuccessful course of convalescent plasma treatment. In vitro, the spike double mutant bearing both ΔH69/ΔV70 and D796H conferred modestly decreased sensitivity to convalescent plasma, while maintaining infectivity levels that were similar to the wild-type virus.The spike substitution mutant D796H appeared to be the main contributor to the decreased susceptibility to neutralizing antibodies, but this mutation resulted in an infectivity defect. The spike deletion mutant ΔH69/ΔV70 had a twofold higher level of infectivity than wild-type SARS-CoV-2, possibly compensating for the reduced infectivity of the D796H mutation. These data reveal strong selection on SARS-CoV-2 during convalescent plasma therapy, which is associated with the emergence of viral variants that show evidence of reduced susceptibility to neutralizing antibodies in immunosuppressed individuals.

Published
2021

4. Proteomic analysis of circulating immune cells identifies cellular phenotypes associated with COVID-19 severity

Author

Potts, Martin, Fletcher-Etherington, Alice, Nightingale, Katie, Mescia, Federica, Bergamaschi, Laura, Calero-Nieto, Fernando J., Antrobus, Robin, Williamson, James, Parsons, Harriet, Huttlin, Edward L., Kingston, Nathalie, Göttgens, Berthold, Bradley, John R., Lehner, Paul J., Matheson, Nicholas J., Smith, Kenneth G.C., Wills, Mark R., Lyons, Paul A., and Weekes, Michael P.

Published
2023
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7. A prospective study of risk factors associated with seroprevalence of SARS-CoV-2 antibodies in healthcare workers at a large UK teaching hospital

Author

Cooper, Daniel J, Lear, Sara, Watson, Laura, Shaw, Ashley, Ferris, Mark, Doffinger, Rainer, Bousfield, Rachel, Sharrocks, Katherine, Weekes, Michael P., Warne, Ben, Sparkes, Dominic, Jones, Nick K, Rivett, Lucy, Routledge, Matthew, Chaudhry, Afzal, Dempsey, Katherine, Matson, Montgomery, Lakha, Adil, Gathercole, George, O'Connor, Olivia, Wilson, Emily, Shahzad, Orthi, Toms, Kieran, Thompson, Rachel, Halsall, Ian, Halsall, David, Houghton, Sally, Papadia, Sofia, Kingston, Nathalie, Stirrups, Kathleen E, Graves, Barbara, Townsend, Paul, Walker, Neil, Stark, Hannah, De Angelis, Daniela, Seaman, Shaun, Dougan, Gordon, Bradley, John R, Török, M. Estée, Goodfellow, Ian, and Baker, Stephen

Published
2022
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8. SARS-CoV-2 spike N-terminal domain modulates TMPRSS2-dependent viral entry and fusogenicity

Author

Baker, Stephen, Dougan, Gordon, Hess, Christoph, Kingston, Nathalie, Lehner, Paul J., Lyons, Paul A., Matheson, Nicholas J., Owehand, Willem H., Saunders, Caroline, Summers, Charlotte, Thaventhiran, James E.D., Toshner, Mark, Weekes, Michael P., Maxwell, Patrick, Shaw, Ashley, Bucke, Ashlea, Calder, Jo, Canna, Laura, Domingo, Jason, Elmer, Anne, Fuller, Stewart, Harris, Julie, Hewitt, Sarah, Kennet, Jane, Jose, Sherly, Kourampa, Jenny, Meadows, Anne, O’Brien, Criona, Price, Jane, Publico, Cherry, Rastall, Rebecca, Ribeiro, Carla, Rowlands, Jane, Ruffolo, Valentina, Tordesillas, Hugo, Bullman, Ben, Dunmore, Benjamin J., Fawke, Stuart, Gräf, Stefan, Hodgson, Josh, Huang, Christopher, Hunter, Kelvin, Jones, Emma, Legchenko, Ekaterina, Matara, Cecilia, Martin, Jennifer, Mescia, Federica, O’Donnell, Ciara, Pointon, Linda, Shih, Joy, Sutcliffe, Rachel, Tilly, Tobias, Treacy, Carmen, Tong, Zhen, Wood, Jennifer, Wylot, Marta, Betancourt, Ariana, Bower, Georgie, Cossetti, Chiara, De Sa, Aloka, Epping, Madeline, Gleadall, Nick, Grenfell, Richard, Hinch, Andrew, Jackson, Sarah, Jarvis, Isobel, Krishna, Ben, Nice, Francesca, Omarjee, Ommar, Perera, Marianne, Potts, Martin, Richoz, Nathan, Romashova, Veronika, Stefanucci, Luca, Strezlecki, Mateusz, Turner, Lori, De Bie, Eckart M.D.D., Bunclark, Katherine, Josipovic, Masa, Mackay, Michael, Allison, John, Butcher, Helen, Caputo, Daniela, Clapham-Riley, Debbie, Dewhurst, Eleanor, Furlong, Anita, Graves, Barbara, Gray, Jennifer, Ivers, Tasmin, Le Gresley, Emma, Linger, Rachel, Meloy, Sarah, Muldoon, Francesca, Ovington, Nigel, Papadia, Sofia, Phelan, Isabel, Stark, Hannah, Stirrups, Kathleen E., Townsend, Paul, Walker, Neil, Webster, Jennifer, Scholtes, Ingrid, Hein, Sabine, King, Rebecca, Meng, Bo, Datir, Rawlings, Choi, Jinwook, Bradley, John R., Smith, Kenneth G.C., Lee, Joo Hyeon, and Gupta, Ravindra K.

Published
2022
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9. Epstein-Barr virus BALF0/1 subverts the Caveolin and ERAD pathways to target B cell receptor complexes for degradation.

Author

Pei Tung Yiu, Stephanie, Yifei Liao, Jinjie Yan, Weekes, Michael P., and Gewurz, Benjamin E.

Subjects
B cell receptors, B cells, IMMUNOGLOBULIN heavy chains, B cell lymphoma, CAVEOLAE
Abstract

Epstein-Barr virus (EBV) establishes persistent infection, causes infectious mononucleosis, is a major trigger for multiple sclerosis and contributes to multiple cancers. Yet, knowledge remains incomplete about how the virus remodels host B cells to support lytic replication. We previously identified that EBV lytic replication results in selective depletion of plasma membrane (PM) B cell receptor (BCR) complexes, composed of immunoglobulin and the CD79A and CD79B signaling chains. Here, we used proteomic and biochemical approaches to identify that the EBV early lytic protein BALF0/1 is responsible for EBV lytic cycle BCR degradation. Mechanistically, an immunoglobulin heavy chain (HC) cytoplasmic tail KVK motif was required for ubiquitin-mediated BCR degradation, while CD79A and CD79B were dispensable. BALF0/1 subverted caveolin-mediated endocytosis to internalize PM BCR complexes and to deliver them to the endoplasmic reticulum. BALF0/1 stimulated immunoglobulin HC cytoplasmic tail ubiquitination, which together with the ATPase valosin-containing protein/p97 drove ER-associated degradation of BCR complexes by cytoplasmic proteasomes. BALF0/1 knockout reduced the viral load of secreted EBV particles from B cells that expressed a monoclonal antibody against EBV glycoprotein 350 but not a control anti-influenza hemagglutinin antibody and increased viral particle immunoglobulin incorporation. Consistent with downmodulation of PM BCR, BALF0/1 overexpression reduced viability of a diffuse large B cell lymphoma cell line whose survival is dependent upon BCR signaling. Collectively, our results suggest that EBV BALF0/1 downmodulates immunoglobulin upon lytic reactivation to block BCR signaling and support virion release, but await the development of suitable models to test its roles in EBV reactivation in vivo. [ABSTRACT FROM AUTHOR]

Published
2025
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10. Coagulation factor V is a T-cell inhibitor expressed by leukocytes in COVID-19

Author

Wang, Jun, Kotagiri, Prasanti, Lyons, Paul A., Al-Lamki, Rafia S., Mescia, Federica, Bergamaschi, Laura, Turner, Lorinda, Morgan, Michael D., Calero-Nieto, Fernando J., Bach, Karsten, Mende, Nicole, Wilson, Nicola K., Watts, Emily R., Maxwell, Patrick H., Chinnery, Patrick F., Kingston, Nathalie, Papadia, Sofia, Stirrups, Kathleen E., Walker, Neil, Gupta, Ravindra K., Menon, David K., Allinson, Kieren, Aitken, Sarah J., Toshner, Mark, Weekes, Michael P., Nathan, James A., Walmsley, Sarah R., Ouwehand, Willem H., Kasanicki, Mary, Göttgens, Berthold, Marioni, John C., Smith, Kenneth G.C., Pober, Jordan S., and Bradley, John R.

Published
2022
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12. Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

Author

Aggarwal, Dinesh, Warne, Ben, Jahun, Aminu S., Hamilton, William L., Fieldman, Thomas, du Plessis, Louis, Hill, Verity, Blane, Beth, Watkins, Emmeline, Wright, Elizabeth, Hall, Grant, Ludden, Catherine, Myers, Richard, Hosmillo, Myra, Chaudhry, Yasmin, Pinckert, Malte L., Georgana, Iliana, Izuagbe, Rhys, Leek, Danielle, Nsonwu, Olisaeloka, Hughes, Gareth J., Packer, Simon, Page, Andrew J., Metaxaki, Marina, Fuller, Stewart, Weale, Gillian, Holgate, Jon, Brown, Christopher A., Howes, Rob, McFarlane, Duncan, Dougan, Gordon, Pybus, Oliver G., Angelis, Daniela De, Maxwell, Patrick H., Peacock, Sharon J., Weekes, Michael P., Illingworth, Chris, Harrison, Ewan M., Matheson, Nicholas J., and Goodfellow, Ian G.

Published
2022
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15. Hypoxia inducible factors regulate hepatitis B virus replication by activating the basal core promoter

Author

Wing, Peter A.C., Liu, Peter Jianrui, Harris, James M., Magri, Andrea, Michler, Thomas, Zhuang, Xiaodong, Borrmann, Helene, Minisini, Rosalba, Frampton, Nicholas R., Wettengel, Jochen M., Mailly, Laurent, D’Arienzo, Valentina, Riedl, Tobias, Nobre, Luis, Weekes, Michael P., Pirisi, Mario, Heikenwalder, Mathias, Baumert, Thomas F., Hammond, Ester M., Mole, David R., Protzer, Ulrike, Balfe, Peter, and McKeating, Jane A.

Published
2021
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16. Longitudinal analysis reveals that delayed bystander CD8+ T cell activation and early immune pathology distinguish severe COVID-19 from mild disease

Author

Bergamaschi, Laura, Mescia, Federica, Turner, Lorinda, Hanson, Aimee L., Kotagiri, Prasanti, Dunmore, Benjamin J., Ruffieux, Hélène, De Sa, Aloka, Huhn, Oisín, Morgan, Michael D., Gerber, Pehuén Pereyra, Wills, Mark R., Baker, Stephen, Calero-Nieto, Fernando J., Doffinger, Rainer, Dougan, Gordon, Elmer, Anne, Goodfellow, Ian G., Gupta, Ravindra K., Hosmillo, Myra, Hunter, Kelvin, Kingston, Nathalie, Lehner, Paul J., Matheson, Nicholas J., Nicholson, Jeremy K., Petrunkina, Anna M., Richardson, Sylvia, Saunders, Caroline, Thaventhiran, James E.D., Toonen, Erik J.M., Weekes, Michael P., Göttgens, Berthold, Toshner, Mark, Hess, Christoph, Bradley, John R., Lyons, Paul A., and Smith, Kenneth G.C.

Published
2021
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17. Rapid implementation of SARS-CoV-2 sequencing to investigate cases of health-care associated COVID-19: a prospective genomic surveillance study

Author

Meredith, Luke W, Hamilton, William L, Warne, Ben, Houldcroft, Charlotte J, Hosmillo, Myra, Jahun, Aminu S, Curran, Martin D, Parmar, Surendra, Caller, Laura G, Caddy, Sarah L, Khokhar, Fahad A, Yakovleva, Anna, Hall, Grant, Feltwell, Theresa, Forrest, Sally, Sridhar, Sushmita, Weekes, Michael P, Baker, Stephen, Brown, Nicholas, Moore, Elinor, Popay, Ashley, Roddick, Iain, Reacher, Mark, Gouliouris, Theodore, Peacock, Sharon J, Dougan, Gordon, Török, M Estée, and Goodfellow, Ian

Published
2020
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19. Point of Care Nucleic Acid Testing for SARS-CoV-2 in Hospitalized Patients: A Clinical Validation Trial and Implementation Study

Author

Baker, Stephen, Bradley, John, Dougan, Gordon, Goodfellow, Ian, Gupta, Ravindra K., Lehner, Paul J., Lyons, Paul, Matheson, Nicholas J., Smith, Kenneth G.C., Toshner, Mark, Weekes, Michael P., Brown, Nick, Curran, Martin, Palmar, Surendra, Zhang, Hongyi, Enoch, David, Chapman, Daniel, Shaw, Ashley, Mendoza, Vivien, Jose, Sherly, Bermperi, Areti, Zerrudo, Julie Ann, Kourampa, Evgenia, Saunders, Caroline, de Jesus, Ranalie, Domingo, Jason, Pasquale, Ciro, Vergese, Bensi, Vargas, Phoebe, Fabiculana, Marivic, Perales, Marlyn, Skells, Richard, Mynott, Lee, Blake, Elizabeth, Bates, Amy, Vallier, Anne-laure, Williams, Alexandra, Phillips, David, Chiu, Edmund, Overhill, Alex, Ramenante, Nicola, Sipple, Jamal, Frost, Steven, Knock, Helena, Hardy, Richard, Foster, Emily, Davidson, Fiona, Rundell, Viona, Bundi, Purity, Abeseabe, Richmond, Clark, Sarah, Vicente, Isabel, Collier, Dami A., Assennato, Sonny M., Warne, Ben, Sithole, Nyarie, Sharrocks, Katherine, Ritchie, Allyson, Ravji, Pooja, Routledge, Matthew, Sparkes, Dominic, Skittrall, Jordan, Smielewska, Anna, Ramsey, Isobel, Goel, Neha, Tassell, Rhys, Lineham, Michelle, Vaghela, Devan, Leong, Clare, Mok, Hoi Ping, Mendoza, Vivienne, Demiris, Nikos, Besser, Martin, Siedner, Mark J., Waddington, Claire S., and Lee, Helen

Published
2020
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21. Highly Multiplexed Proteomic Analysis of HCMV-Infected Dendritic Cells Reveals Global Manipulation of Adaptive Immunity and Host Restriction of Viral Replication

Author

Kerr-Jones, Lauren, primary, Soday, Lior, additional, Cwyfan-Hughes, Nia, additional, Wang, Xinyue, additional, Hunter, Leah, additional, Antrobus, Robin, additional, Miners, Kelly, additional, Ladell, Kristin, additional, Price, David A, additional, Fielding, Ceri A, additional, Wang, Eddie CY, additional, Weekes, Michael P, additional, and Stanton, Richard J, additional

Published
2024
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22. Human cytomegalovirus degrades DMXL1 to inhibit autophagy, lysosomal acidification, and viral assembly

Author

Li, Hanqi, primary, Fletcher-Etherington, Alice, additional, Hunter, Leah M., additional, Keshri, Swati, additional, Fielding, Ceri A., additional, Nightingale, Katie, additional, Ravenhill, Benjamin, additional, Nobre, Luis, additional, Potts, Martin, additional, Antrobus, Robin, additional, Crump, Colin M., additional, Rubinsztein, David C., additional, Stanton, Richard J., additional, and Weekes, Michael P., additional

Published
2024
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27. Suppression of costimulation by human cytomegalovirus promotes evasion of cellular immune defenses

Author

Wang, Eddie C. Y., Pjechova, Mariana, Nightingale, Katie, Vlahava, Virginia-Maria, Patel, Mihil, Ruckova, Eva, Forbes, Simone K., Nobre, Luis, Antrobus, Robin, Roberts, Dawn, Fielding, Ceri A., Seirafian, Sepehr, Davies, James, Murrell, Isa, Lau, Betty, Wilkie, Gavin S., Suárez, Nicolás M., Stanton, Richard J., Vojtesek, Borivoj, Davison, Andrew, Lehner, Paul J., Weekes, Michael P., Wilkinson, Gavin W. G., and Tomasec, Peter

Published
2018

28. High-Definition Analysis of Host Protein Stability during Human Cytomegalovirus Infection Reveals Antiviral Factors and Viral Evasion Mechanisms

Author

Nightingale, Katie, Lin, Kai-Min, Ravenhill, Benjamin J., Davies, Colin, Nobre, Luis, Fielding, Ceri A., Ruckova, Eva, Fletcher-Etherington, Alice, Soday, Lior, Nichols, Hester, Sugrue, Daniel, Wang, Eddie C.Y., Moreno, Pablo, Umrania, Yagnesh, Huttlin, Edward L., Antrobus, Robin, Davison, Andrew J., Wilkinson, Gavin W.G., Stanton, Richard J., Tomasec, Peter, and Weekes, Michael P.

Published
2018
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29. Transferrin receptor 1 is a reticulocyte-specific receptor for Plasmodium vivax

Author

Gruszczyk, Jakub, Kanjee, Usheer, Chan, Li-Jin, Menant, Sébastien, Malleret, Benoit, Lim, Nicholas T. Y., Schmidt, Christoph Q., Mok, Yee-Foong, Lin, Kai-Min, Pearson, Richard D., Rangel, Gabriel, Smith, Brian J., Call, Melissa J., Weekes, Michael P., Griffin, Michael D. W., Murphy, James M., Abraham, Jonathan, Sriprawat, Kanlaya, Menezes, Maria J., Ferreira, Marcelo U., Russell, Bruce, Renia, Laurent, Duraisingh, Manoj T., and Tham, Wai-Hong

Published
2018

31. HCMV-secreted glycoprotein gpUL4 inhibits TRAIL-mediated apoptosis and NK cell activation

Author

Vlachava, Virginia-Maria, primary, Seirafian, Sepehr, additional, Fielding, Ceri A., additional, Kollnberger, Simon, additional, Aicheler, Rebecca J., additional, Hughes, Joseph, additional, Baker, Alexander, additional, Weekes, Michael P., additional, Forbes, Simone, additional, Wilkinson, Gavin W. G., additional, Wang, Eddie C. Y., additional, and Stanton, Richard J., additional

Published
2023
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35. ADAM17 targeting by human cytomegalovirus remodels the cell surface proteome to simultaneously regulate multiple immune pathways

Author

Rubina, Anzelika, primary, Patel, Mihil, additional, Nightingale, Katie, additional, Potts, Martin, additional, Fielding, Ceri A., additional, Kollnberger, Simon, additional, Lau, Betty, additional, Ladell, Kristin, additional, Miners, Kelly L., additional, Nichols, Jenna, additional, Nobre, Luis, additional, Roberts, Dawn, additional, Trinca, Terrence M., additional, Twohig, Jason P., additional, Vlahava, Virginia-Maria, additional, Davison, Andrew J., additional, Price, David A., additional, Tomasec, Peter, additional, Wilkinson, Gavin W. G., additional, Weekes, Michael P., additional, Stanton, Richard J., additional, and Wang, Eddie C. Y., additional

Published
2023
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37. Strain-Dependent Restriction of Human Cytomegalovirus by Zinc Finger Antiviral Proteins

Author

Lista, Maria Jose, primary, Witney, Adam A., additional, Nichols, Jenna, additional, Davison, Andrew J., additional, Wilson, Harry, additional, Latham, Katie A., additional, Ravenhill, Benjamin J., additional, Nightingale, Katie, additional, Stanton, Richard J., additional, Weekes, Michael P., additional, Neil, Stuart J. D., additional, Swanson, Chad M., additional, and Strang, Blair L., additional

Published
2023
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40. Monoclonal antibodies targeting nonstructural viral antigens can activate ADCC against human cytomegalovirus

Author

Vlahava, Virginia-Maria, Murrell, Isa, Zhuang, Lihui, Aicheler, Rebecca J., Lim, Eleanor, Miners, Kelly L., Ladell, Kristin, Suarez, Nicolas M., Price, David A., Davison, Andrew J., Wilkinson, Gavin W.G., Wills, Mark R., Weekes, Michael P., Wang, Eddie C.Y., and Stanton, Richard J.

Subjects
Care and treatment, Development and progression, Genetic aspects, Health aspects, Killer cells -- Genetic aspects -- Health aspects, Monoclonal antibodies -- Health aspects, Viral antigens -- Health aspects, Immune response -- Genetic aspects, Cytomegalovirus infections -- Development and progression -- Care and treatment -- Genetic aspects
Abstract

Introduction Human cytomegalovirus (HCMV) establishes lifelong infection in the face of robust humoral and cell-mediated immune responses. The virus is a significant cause of morbidity and mortality in immunocompromised individuals [...], Human cytomegalovirus (HCMV) is a ubiquitous pathogen that causes severe disease following congenital infection and in immunocompromised individuals. No vaccines are licensed, and there are limited treatment options. We now show that the addition of anti-HCMV antibodies (Abs) can activate NK cells prior to the production of new virions, through Ab- dependent cellular cytotoxicity (ADCC), overcoming viral immune evasins. Quantitative proteomics defined the most abundant HCMV proteins on the cell surface, and we screened these targets to identify the viral antigens responsible for activating ADCC. Surprisingly, these were not structural glycoproteins; instead, the immune evasins US28, RL11, UL5, UL141, and UL16 each individually primed ADCC. We isolated human monoclonal Abs (mAbs) specific for UL16 or UL141 from a seropositive donor and optimized them for ADCC. Cloned Abs targeting a single antigen (UL141) were sufficient to mediate ADCC against HCMV-infected cells, even at low concentrations. Collectively, these findings validated an unbiased methodological approach to the identification of immunodominant viral antigens, providing a pathway toward an immunotherapeutic strategy against HCMV and potentially other pathogens.

Published
2021
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42. Human Cytomegalovirus Degrades DMXL1 to Inhibit Autophagy, Lysosomal Acidification and Viral Assembly

Author

Li, Hanqi, primary, Fletcher-Etherington, Alice, additional, Hunter, Leah, additional, Keshri, Swati, additional, Fielding, Ceri A., additional, Nightingale, Katie, additional, Ravenhill, Benjamin, additional, Nobre, Luis, additional, Antrobus, Robin, additional, Rubinsztein, David C., additional, Stanton, Richard J., additional, and Weekes, Michael P., additional

Published
2023
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43. Demographic, behavioural and occupational risk factors associated with SARS-CoV-2 infection in UK healthcare workers: a retrospective observational study

Author

Cooper, Daniel James, Lear, Sara, Sithole, Nyarie, Shaw, Ashley, Stark, Hannah, Ferris, Mark, CITIID-NIHR BioResource COVID-19 Collaboration Consortium, Bradley, John, Maxwell, Patrick, Goodfellow, Ian, Weekes, Michael P, Seaman, Shaun, Baker, Stephen, Cooper, Daniel James [0000-0002-3643-7605], Ferris, Mark [0000-0001-5040-4263], Seaman, Shaun [0000-0003-3726-5937], and Apollo - University of Cambridge Repository

Subjects
Public health, Epidemiology, SARS-CoV-2, Health Personnel, COVID-19, Infection control, Antibodies, Viral, United Kingdom, FOS: Sociology, Risk Factors, Infectious diseases, Humans, Retrospective Studies, Demography
Abstract

Peer reviewed: True, Acknowledgements: We thank National Institute for Health Research (NIHR) BioResource volunteers for their participation, and gratefully acknowledge NIHR BioResource centres, NHS trusts and staff for their contribution. We thank the NIHR, NHS Blood and Transplant, and Health Data Research UK as part of the Digital Innovation Hub Programme., OBJECTIVE: Healthcare workers (HCWs) are at higher risk of SARS-CoV-2 infection than the general population. This group is pivotal to healthcare system resilience during the COVID-19, and future, pandemics. We investigated demographic, social, behavioural and occupational risk factors for SARS-CoV-2 infection among HCWs. DESIGN/SETTING/PARTICIPANTS: HCWs enrolled in a large-scale sero-epidemiological study at a UK university teaching hospital were sent questionnaires spanning a 5-month period from March to July 2020. In a retrospective observational cohort study, univariate logistic regression was used to assess factors associated with SARS-CoV-2 infection. A Least Absolute Shrinkage Selection Operator regression model was used to identify variables to include in a multivariate logistic regression model. RESULTS: Among 2258 HCWs, highest ORs associated with SARS-CoV-2 antibody seropositivity on multivariate analysis were having a household member previously testing positive for SARS-CoV-2 antibodies (OR 6.94 (95% CI 4.15 to 11.6); p

Published
2022
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44. HCMV pUL135 Remodels the Actin Cytoskeleton to Impair Immune Recognition of Infected Cells

Author

Stanton, Richard J., Prod’homme, Virginie, Purbhoo, Marco A., Moore, Melanie, Aicheler, Rebecca J., Heinzmann, Marcus, Bailer, Susanne M., Haas, Jürgen, Antrobus, Robin, Weekes, Michael P., Lehner, Paul J., Vojtesek, Borivoj, Miners, Kelly L., Man, Stephen, Wilkie, Gavin S., Davison, Andrew J., Wang, Eddie C.Y., Tomasec, Peter, and Wilkinson, Gavin W.G.

Published
2014
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48. Human cytomegalovirus: taking the strain

Author

Wilkinson, Gavin W. G., Davison, Andrew J., Tomasec, Peter, Fielding, Ceri A., Aicheler, Rebecca, Murrell, Isa, Seirafian, Sepher, Wang, Edward C. Y., Weekes, Michael, Lehner, Paul J., Wilkie, Gavin S., and Stanton, Richard J.

Published
2015
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50. SARS-CoV-2 spike N-terminal domain modulates TMPRSS2-dependent viral entry and fusogenicity

Author

Meng, Bo, primary, Datir, Rawlings, additional, Choi, Jinwook, additional, Bradley, John R., additional, Smith, Kenneth G.C., additional, Lee, Joo Hyeon, additional, Gupta, Ravindra K., additional, Baker, Stephen, additional, Dougan, Gordon, additional, Hess, Christoph, additional, Kingston, Nathalie, additional, Lehner, Paul J., additional, Lyons, Paul A., additional, Matheson, Nicholas J., additional, Owehand, Willem H., additional, Saunders, Caroline, additional, Summers, Charlotte, additional, Thaventhiran, James E.D., additional, Toshner, Mark, additional, Weekes, Michael P., additional, Maxwell, Patrick, additional, Shaw, Ashley, additional, Bucke, Ashlea, additional, Calder, Jo, additional, Canna, Laura, additional, Domingo, Jason, additional, Elmer, Anne, additional, Fuller, Stewart, additional, Harris, Julie, additional, Hewitt, Sarah, additional, Kennet, Jane, additional, Jose, Sherly, additional, Kourampa, Jenny, additional, Meadows, Anne, additional, O’Brien, Criona, additional, Price, Jane, additional, Publico, Cherry, additional, Rastall, Rebecca, additional, Ribeiro, Carla, additional, Rowlands, Jane, additional, Ruffolo, Valentina, additional, Tordesillas, Hugo, additional, Bullman, Ben, additional, Dunmore, Benjamin J., additional, Fawke, Stuart, additional, Gräf, Stefan, additional, Hodgson, Josh, additional, Huang, Christopher, additional, Hunter, Kelvin, additional, Jones, Emma, additional, Legchenko, Ekaterina, additional, Matara, Cecilia, additional, Martin, Jennifer, additional, Mescia, Federica, additional, O’Donnell, Ciara, additional, Pointon, Linda, additional, Shih, Joy, additional, Sutcliffe, Rachel, additional, Tilly, Tobias, additional, Treacy, Carmen, additional, Tong, Zhen, additional, Wood, Jennifer, additional, Wylot, Marta, additional, Betancourt, Ariana, additional, Bower, Georgie, additional, Cossetti, Chiara, additional, De Sa, Aloka, additional, Epping, Madeline, additional, Gleadall, Nick, additional, Grenfell, Richard, additional, Hinch, Andrew, additional, Jackson, Sarah, additional, Jarvis, Isobel, additional, Krishna, Ben, additional, Nice, Francesca, additional, Omarjee, Ommar, additional, Perera, Marianne, additional, Potts, Martin, additional, Richoz, Nathan, additional, Romashova, Veronika, additional, Stefanucci, Luca, additional, Strezlecki, Mateusz, additional, Turner, Lori, additional, De Bie, Eckart M.D.D., additional, Bunclark, Katherine, additional, Josipovic, Masa, additional, Mackay, Michael, additional, Allison, John, additional, Butcher, Helen, additional, Caputo, Daniela, additional, Clapham-Riley, Debbie, additional, Dewhurst, Eleanor, additional, Furlong, Anita, additional, Graves, Barbara, additional, Gray, Jennifer, additional, Ivers, Tasmin, additional, Le Gresley, Emma, additional, Linger, Rachel, additional, Meloy, Sarah, additional, Muldoon, Francesca, additional, Ovington, Nigel, additional, Papadia, Sofia, additional, Phelan, Isabel, additional, Stark, Hannah, additional, Stirrups, Kathleen E., additional, Townsend, Paul, additional, Walker, Neil, additional, Webster, Jennifer, additional, Scholtes, Ingrid, additional, Hein, Sabine, additional, and King, Rebecca, additional

Published
2022
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