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131 results on '"Goodfellow I"'

1. Reply to Kempf et al

Author: Thorne, L. and Goodfellow, I.
Published: 2017

2. Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts tropism and fusogenicity

Author: Meng, B., Abdullahi, A., Ferreira, I., Goonawardane, N., Saito, A., Kimura, I., Yamasoba, D., Gerber, P., Fatihi, S., Rathore, S., Zepeda, S., Papa, G., Kemp, S., Ikeda, T., Toyoda, M., Tan, T., Kuramochi, J., Mitsunaga, S., Ueno, T., Shirakawa, K., Takaori-Kondo, A., Brevini, T., Mallery, D., Charles, O., Collaboration, C., Japan, G., Consortium, E., Bowen, J., Joshi, A., Walls, A., Jackson, L., Martin, D., Smith, K., Bradley, J., Briggs, J., Choi, J., Madissoon, E., Meyer, K., Mlcochova, P., Ceron-Gutierrez, L., Doffinger, R., Teichmann, S., Fisher, A., Pizzuto, M., de Marco, A., Corti, D., Hosmillo, M., Lee, J., James, L., Thukral, L., Veesler, D., Sigal, A., Sampaziotis, F., Goodfellow, I., Matheson, N., Sato, K., and Gupta, R.
Subjects: Immune evasion, SARS-CoV-2
Abstract: The SARS-CoV-2 Omicron BA.1 variant emerged in 20211 and bears multiple spike mutations2. Here we show that Omicron spike has higher affinity for ACE2 compared to Delta as well as a marked change of antigenicity conferring significant evasion of therapeutic monoclonal and vaccine-elicited polyclonal neutralising antibodies after two doses. mRNA vaccination as a third vaccine dose rescues and broadens neutralisation. Importantly, antiviral drugs remdesivir and molnupiravir retain efficacy against Omicron BA.1. Replication was similar for Omicron and Delta virus isolates in human nasal epithelial cultures. However, in lower airway organoids, lung cells and gut cells, Omicron demonstrated lower replication. Omicron spike protein was less efficiently cleaved compared to Delta. Replication differences mapped to entry efficiency using spike pseudotyped virus (PV) assays. The defect for Omicron PV to enter specific cell types effectively correlated with higher cellular RNA expression of TMPRSS2, and knock down of TMPRSS2 impacted Delta entry to a greater extent than Omicron. Furthermore, drug inhibitors targeting specific entry pathways3 demonstrated that the Omicron spike inefficiently utilises the cellular protease TMPRSS2 that promotes cell entry via plasma membrane fusion, with greater dependency on cell entry via the endocytic pathway. Consistent with suboptimal S1/S2 cleavage and inability to utilise TMPRSS2, syncytium formation by the Omicron spike was markedly impaired compared to the Delta spike. Omicron’s less efficient spike cleavage at S1/S2 is associated with shift in cellular tropism away from TMPRSS2 expressing cells, with implications for altered pathogenesis., SARS-CoV-2オミクロン株による中和抗体回避と感染指向性の変化. 京都大学プレスリリース. 2022-02-03.
Published: 2022

3. Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity

Author: Meng, B., Abdullahi, A., Ferreira, I. A. T. M., Goonawardane, N., Saito, A., Kimura, I., Yamasoba, D., Gerber, P. P., Fatihi, S., Rathore, S., Zepeda, S. K., Papa, G., Kemp, S. A., Ikeda, T., Toyoda, M., Tan, T. S., Kuramochi, J., Mitsunaga, S., Ueno, T., Shirakawa, K., Takaori-Kondo, A., Brevini, T., Mallery, D. L., Charles, O. J., Baker, S., Dougan, G., Hess, C., Kingston, N., Lehner, P. J., Lyons, P. A., Matheson, N. J., Ouwehand, W. H., Saunders, C., Summers, C., Thaventhiran, J. E. D., Toshner, M., Weekes, M. P., Maxwell, P., Shaw, A., Bucke, A., Calder, J., Canna, L., Domingo, J., Elmer, A., Fuller, S., Harris, J., Hewitt, S., Kennet, J., Jose, S., Kourampa, J., Meadows, A., O'Brien, C., Price, J., Publico, C., Rastall, R., Ribeiro, C., Rowlands, J., Ruffolo, V., Tordesillas, H., Bullman, B., Dunmore, B. J., Graf, S., Hodgson, J., Huang, C., Hunter, K., Jones, E., Legchenko, E., Matara, C., Martin, J., Mescia, F., O'Donnell, C., Pointon, L., Shih, J., Sutcliffe, R., Tilly, T., Treacy, C., Tong, Z., Wood, J., Wylot, M., Betancourt, A., Bower, G., Cossetti, C., De Sa, A., Epping, M., Fawke, S., Gleadall, N., Grenfell, R., Hinch, A., Jackson, S., Jarvis, I., Krishna, B., Nice, F., Omarjee, O., Perera, M., Potts, M., Richoz, N., Romashova, V., Stefanucci, L., Strezlecki, M., Turner, L., De Bie, E. M. D. D., Bunclark, K., Josipovic, M., Mackay, M., Butcher, H., Caputo, D., Chandler, M., Chinnery, P., Clapham-Riley, D., Dewhurst, E., Fernandez, C., Furlong, A., Graves, B., Gray, J., Hein, S., Ivers, T., Le Gresley, E., Linger, R., Kasanicki, M., King, R., Meloy, S., Moulton, A., Muldoon, F., Ovington, N., Papadia, S., Penkett, C. J., Phelan, I., Ranganath, V., Paraschiv, R., Sage, A., Sambrook, J., Scholtes, I., Schon, K., Stark, H., Stirrups, K. E., Townsend, P., Walker, N., Webster, J., Butlertanaka, E. P., Tanaka, Y. L., Ito, J., Uriu, K., Kosugi, Y., Suganami, M., Oide, A., Yokoyama, M., Chiba, M., Motozono, C., Nasser, H., Shimizu, R., Kitazato, K., Hasebe, H., Irie, T., Nakagawa, S., Wu, J., Takahashi, M., Fukuhara, T., Shimizu, K., Tsushima, K., Kubo, H., Kazuma, Y., Nomura, R., Horisawa, Y., Nagata, K., Kawai, Y., Yanagida, Y., Tashiro, Y., Tokunaga, K., Ozono, S., Kawabata, R., Morizako, N., Sadamasu, K., Asakura, H., Nagashima, M., Yoshimura, K., Cardenas, P., Munoz, E., Barragan, V., Marquez, S., Prado-Vivar, B., Becerra-Wong, M., Caravajal, M., Trueba, G., Rojas-Silva, P., Grunauer, M., Gutierrez, B., Guadalupe, J. J., Fernandez-Cadena, J. C., Andrade-Molina, D., Baldeon, M., Pinos, A., Bowen, J. E., Joshi, A., Walls, A. C., Jackson, L., Martin, D., Smith, K. G. C., Bradley, J., Briggs, J. A. G., Choi, J., Madissoon, E., Meyer, K. B., Mlcochova, P., Ceron-Gutierrez, L., Doffinger, R., Teichmann, S. A., Fisher, A. J., Pizzuto, M. S., de Marco, A., Corti, D., Hosmillo, M., Lee, J. H., James, L. C., Thukral, L., Veesler, D., Sigal, A., Sampaziotis, F., Goodfellow, I. G., Sato, K., and Gupta, R. K.
Subjects: Adult, Male, COVID-19 Vaccines, Virus Replication, Membrane Fusion, Antibodies, Cell Line, Tissue Culture Techniques, Chlorocebus aethiops, 80 and over, Animals, Humans, Viral, Neutralizing, Lung, Aged, Multidisciplinary, Virulence, SARS-CoV-2, Immune Sera, Cell Membrane, Serine Endopeptidases, COVID-19, Convalescence, Middle Aged, Virus Internalization, Spike Glycoprotein, Intestines, Coronavirus, Nasal Mucosa, Mutation, Female, Angiotensin-Converting Enzyme 2, Aged, 80 and over, Antibodies, Neutralizing, Antibodies, Viral, Spike Glycoprotein, Coronavirus
Abstract: The SARS-CoV-2 Omicron BA.1 variant emerged in 20211 and has multiple mutations in its spike protein2. Here we show that the spike protein of Omicron has a higher affinity for ACE2 compared with Delta, and a marked change in its antigenicity increases Omicron’s evasion of therapeutic monoclonal and vaccine-elicited polyclonal neutralizing antibodies after two doses. mRNA vaccination as a third vaccine dose rescues and broadens neutralization. Importantly, the antiviral drugs remdesivir and molnupiravir retain efficacy against Omicron BA.1. Replication was similar for Omicron and Delta virus isolates in human nasal epithelial cultures. However, in lung cells and gut cells, Omicron demonstrated lower replication. Omicron spike protein was less efficiently cleaved compared with Delta. The differences in replication were mapped to the entry efficiency of the virus on the basis of spike-pseudotyped virus assays. The defect in entry of Omicron pseudotyped virus to specific cell types effectively correlated with higher cellular RNA expression of TMPRSS2, and deletion of TMPRSS2 affected Delta entry to a greater extent than Omicron. Furthermore, drug inhibitors targeting specific entry pathways3 demonstrated that the Omicron spike inefficiently uses the cellular protease TMPRSS2, which promotes cell entry through plasma membrane fusion, with greater dependency on cell entry through the endocytic pathway. Consistent with suboptimal S1/S2 cleavage and inability to use TMPRSS2, syncytium formation by the Omicron spike was substantially impaired compared with the Delta spike. The less efficient spike cleavage of Omicron at S1/S2 is associated with a shift in cellular tropism away from TMPRSS2-expressing cells, with implications for altered pathogenesis.
Published: 2022
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4. The origins and molecular evolution of SARS-CoV-2 lineage B.1.1.7 in the UK (vol 8, veac080, 2022)

Author: Hill, V, Plessis, LD, Peacock, TP, Aggarwal, D, Colquhoun, R, Carabelli, AM, Ellaby, N, Gallagher, E, Groves, N, Jackson, B, McCrone, JT, O'Toole, A, Price, A, Sanderson, T, Scher, E, Southgate, J, Volz, E, Barclay, WS, Barrett, JC, Chand, M, Connor, T, Goodfellow, I, Gupta, RK, Harrison, EM, Loman, N, Myers, R, Robertson, DL, Pybus, OG, and Rambaut, A
Published: 2022

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

Author: Kemp, S. A., Collier, D. A., Datir, R. P., Ferreira, I. A. T. M., Gayed, S., Jahun, A., Hosmillo, M., Rees-Spear, C., Mlcochova, P., Lumb, I. U., Roberts, D. J., Chandra, A., Temperton, N., Baker, S., Dougan, G., Hess, C., Kingston, N., Lehner, P. J., Lyons, P. A., Matheson, N. J., Owehand, W. H., Saunders, C., Summers, C., Thaventhiran, J. E. D., Toshner, M., Weekes, M. P., Bucke, A., Calder, J., Canna, L., Domingo, J., Elmer, A., Fuller, S., Harris, J., Hewitt, S., Kennet, J., Jose, S., Kourampa, J., Meadows, A., O'Brien, C., Price, J., Publico, C., Rastall, R., Ribeiro, C., Rowlands, J., Ruffolo, V., Tordesillas, H., Bullman, B., Dunmore, B. J., Fawke, S., Graf, S., Hodgson, J., Huang, C., Hunter, K., Jones, E., Legchenko, E., Matara, C., Martin, J., Mescia, F., O'Donnell, C., Pointon, L., Pond, N., Shih, J., Sutcliffe, R., Tilly, T., Treacy, C., Tong, Z., Wood, J., Wylot, M., Bergamaschi, L., Betancourt, A., Bower, G., Cossetti, C., De Sa, A., Epping, M., Gleadall, N., Grenfell, R., Hinch, A., Huhn, O., Jackson, S., Jarvis, I., Lewis, D., Marsden, J., Nice, F., Okecha, G., Omarjee, O., Perera, M., Richoz, N., Romashova, V., Yarkoni, N. S., Sharma, R., Stefanucci, L., Stephens, J., Strezlecki, M., Turner, L., De Bie, E. M. D. D., Bunclark, K., Josipovic, M., Mackay, M., Rossi, S., Selvan, M., Spencer, S., Yong, C., Ansaripour, A., Michael, A., Mwaura, L., Patterson, C., Polwarth, G., Polgarova, P., di Stefano, G., Fahey, C., Michel, R., Bong, S. -H., Coudert, J. D., Holmes, E., Allison, J., Butcher, H., Caputo, D., Clapham-Riley, D., Dewhurst, E., Furlong, A., Graves, B., Gray, J., Ivers, T., Kasanicki, M., Le Gresley, E., Linger, R., Meloy, S., Muldoon, F., Ovington, N., Papadia, S., Phelan, I., Stark, H., Stirrups, K. E., Townsend, P., Walker, N., Webster, J., Robson, S. C., Loman, N. J., Connor, T. R., Golubchik, T., Martinez Nunez, R. T., Ludden, C., Corden, S., Johnston, I., Bonsall, D., Smith, C. P., Awan, A. R., Bucca, G., Estee Torok, M., Saeed, K., Prieto, J. A., Jackson, D. K., Hamilton, W. L., Snell, L. B., Moore, C., Harrison, E. M., Goncalves, S., Fairley, D. J., Loose, M. W., Watkins, J., Livett, R., Moses, S., Amato, R., Nicholls, S., Bull, M., Smith, D. L., Barrett, J., Aanensen, D. M., Curran, M. D., Parmar, S., Aggarwal, D., Shepherd, J. G., Parker, M. D., Glaysher, S., Bashton, M., Underwood, A. P., Pacchiarini, N., Loveson, K. F., Carabelli, A. M., Templeton, K. E., Langford, C. F., Sillitoe, J., de Silva, T. I., Wang, D., Kwiatkowski, D., Rambaut, A., O'Grady, J., Cottrell, S., Holden, M. T. G., Thomson, E. C., Osman, H., Andersson, M., Chauhan, A. J., Hassan-Ibrahim, M. O., Lawniczak, M., Alderton, A., Chand, M., Constantinidou, C., Unnikrishnan, M., Darby, A. C., Hiscox, J. A., Paterson, S., Martincorena, I., Robertson, D. L., Volz, E. M., Page, A. J., Pybus, O. G., Bassett, A. R., Ariani, C. V., Spencer Chapman, M. H., K. K., Li, Shah, R. N., Jesudason, N. G., Taha, Y., Mchugh, M. P., Dewar, R., Jahun, A. S., Mcmurray, C., Pandey, S., Mckenna, J. P., Nelson, A., Young, G. R., Mccann, C. M., Elliott, S., Lowe, H., Temperton, B., Roy, S., Price, A., Rey, S., Wyles, M., Rooke, S., Shaaban, S., de Cesare, M., Letchford, L., Silveira, S., Pelosi, E., Wilson-Davies, E., O'Toole, A., Hesketh, A. R., Stark, R., du Plessis, L., Ruis, C., Adams, H., Bourgeois, Y., Michell, S. L., Gramatopoulos, D., Edgeworth, J., Breuer, J., Todd, J. A., Fraser, C., Buck, D., John, M., Kay, G. L., Palmer, S., Peacock, S. J., Heyburn, D., Weldon, D., Robinson, E., Mcnally, A., Muir, P., Vipond, I. B., Boyes, J., Sivaprakasam, V., Salluja, T., Dervisevic, S., Meader, E. J., Park, N. R., Oliver, K., Jeffries, A. R., Ott, S., da Silva Filipe, A., Simpson, D. A., Williams, C., Masoli, J. A. H., Knight, B. A., Jones, C. R., Koshy, C., Ash, A., Casey, A., Bosworth, A., Ratcliffe, L., Xu-McCrae, L., Pymont, H. M., Hutchings, S., Berry, L., Jones, K., Halstead, F., Davis, T., Holmes, C., Iturriza-Gomara, M., Lucaci, A. O., Randell, P. A., Cox, A., Madona, P., Harris, K. A., Brown, J. R., Mahungu, T. W., Irish-Tavares, D., Haque, T., Hart, J., Witele, E., Fenton, M. L., Liggett, S., Graham, C., Swindells, E., Collins, J., Eltringham, G., Campbell, S., Mcclure, P. C., Clark, G., Sloan, T. J., Jones, C., Lynch, J., Warne, B., Leonard, S., Durham, J., Williams, T., Haldenby, S. T., Storey, N., Alikhan, N. -F., Holmes, N., Carlile, M., Perry, M., Craine, N., Lyons, R. A., Beckett, A. H., Goudarzi, S., Fearn, C., Cook, K., Dent, H., Paul, H., Davies, R., Blane, B., Girgis, S. T., Beale, M. A., Bellis, K. L., Dorman, M. J., Drury, E., Kane, L., Kay, S., Mcguigan, S., Nelson, R., Prestwood, L., Rajatileka, S., Batra, R., Williams, R. J., Kristiansen, M., Green, A., Justice, A., Mahanama, A. I. K., Samaraweera, B., Hadjirin, N. F., Quick, J., Poplawski, R., Kermack, L. M., Reynolds, N., Hall, G., Chaudhry, Y., Pinckert, M. L., Georgana, I., Moll, R. J., Thornton, A., Myers, R., Stockton, J., Williams, C. A., Yew, W. C., Trotter, A. J., Trebes, A., MacIntyre-Cockett, G., Birchley, A., Adams, A., Plimmer, A., Gatica-Wilcox, B., Mckerr, C., Hilvers, E., Jones, H., Asad, H., Coombes, J., Evans, J. M., Fina, L., Gilbert, L., Graham, L., Cronin, M., Kumziene-Summerhayes, S., Taylor, S., Jones, S., Groves, D. C., Zhang, P., Gallis, M., Louka, S. F., Starinskij, I., Jackson, C., Gourtovaia, M., Tonkin-Hill, G., Lewis, K., Tovar-Corona, J. M., James, K., Baxter, L., Alam, M. T., Orton, R. J., Hughes, J., Vattipally, S., Ragonnet-Cronin, M., Nascimento, F. F., Jorgensen, D., Boyd, O., Geidelberg, L., Zarebski, A. E., Raghwani, J., Kraemer, M. U. G., Southgate, J., Lindsey, B. B., Freeman, T. M., Keatley, J. -P., Singer, J. B., de Oliveira Martins, L., Yeats, C. A., Abudahab, K., Taylor, B. E. W., Menegazzo, M., Danesh, J., Hogsden, W., Eldirdiri, S., Kenyon, A., Mason, J., Robinson, T. I., Holmes, A., Hartley, J. A., Curran, T., Mather, A. E., Shankar, G., Jones, R., Howe, R., Morgan, S., Wastenge, E., Chapman, M. R., Mookerjee, S., Stanley, R., Smith, W., Peto, T., Eyre, D., Crook, D., Vernet, G., Kitchen, C., Gulliver, H., Merrick, I., Guest, M., Munn, R., Bradley, D. T., Wyatt, T., Beaver, C., Foulser, L., Churcher, C. M., Brooks, E., Smith, K. S., Galai, K., Mcmanus, G. M., Bolt, F., Coll, F., Meadows, L., Attwood, S. W., Davies, A., De Lacy, E., Downing, F., Edwards, S., Scarlett, G. P., Jeremiah, S., Smith, N., Leek, D., Sridhar, S., Forrest, S., Cormie, C., Gill, H. K., Dias, J., Higginson, E. E., Maes, M., Young, J., Wantoch, M., Jamrozy, D., Lo, S., Patel, M., Hill, V., Bewshea, C. M., Ellard, S., Auckland, C., Harrison, I., Bishop, C., Chalker, V., Richter, A., Beggs, A., Best, A., Percival, B., Mirza, J., Megram, O., Mayhew, M., Crawford, L., Ashcroft, F., Moles-Garcia, E., Cumley, N., Hopes, R., Asamaphan, P., Niebel, M. O., Gunson, R. N., Bradley, A., Maclean, A., Mollett, G., Blacow, R., Bird, P., Helmer, T., Fallon, K., Tang, J., Hale, A. D., Macfarlane-Smith, L. R., Harper, K. L., Carden, H., Machin, N. W., Jackson, K. A., Ahmad, S. S. Y., George, R. P., Turtle, L., O'Toole, E., Watts, J., Breen, C., Cowell, A., Alcolea-Medina, A., Charalampous, T., Patel, A., Levett, L. J., Heaney, J., Rowan, A., Taylor, G. P., Shah, D., Atkinson, L., Lee, J. C. D., Westhorpe, A. P., Jannoo, R., Lowe, H. L., Karamani, A., Ensell, L., Chatterton, W., Pusok, M., Dadrah, A., Symmonds, A., Sluga, G., Molnar, Z., Baker, P., Bonner, S., Essex, S., Barton, E., Padgett, D., Scott, G., Greenaway, J., Payne, B. A. I., Burton-Fanning, S., Waugh, S., Raviprakash, V., Sheriff, N., Blakey, V., Williams, L. -A., Moore, J., Stonehouse, S., Smith, L., Davidson, R. K., Bedford, L., Coupland, L., Wright, V., Chappell, J. G., Tsoleridis, T., Ball, J., Khakh, M., Fleming, V. M., Lister, M. M., Howson-Wells, H. C., Boswell, T., Joseph, A., Willingham, I., Duckworth, N., Walsh, S., Wise, E., Moore, N., Mori, M., Cortes, N., Kidd, S., Williams, R., Gifford, L., Bicknell, K., Wyllie, S., Lloyd, A., Impey, R., Malone, C. S., Cogger, B. J., Levene, N., Monaghan, L., Keeley, A. J., Partridge, D. G., Raza, M., Evans, C., Johnson, K., Abnizova, I., Aigrain, L., Ali, M., Allen, L., Anderson, R., Ariani, C., Austin-Guest, S., Bala, S., Bassett, A., Battleday, K., Beal, J., Beale, M., Bellany, S., Bellerby, T., Bellis, K., Berger, D., Berriman, M., Betteridge, E., Bevan, P., Binley, S., Bishop, J., Blackburn, K., Bonfield, J., Boughton, N., Bowker, S., Brendler-Spaeth, T., Bronner, I., Brooklyn, T., Buddenborg, S. K., Bush, R., Caetano, C., Cagan, A., Carter, N., Cartwright, J., Monteiro, T. C., Chapman, L., Chillingworth, T. -J., Clapham, P., Clark, R., Clarke, A., Clarke, C., Cole, D., Cook, E., Coppola, M., Cornell, L., Cornwell, C., Corton, C., Crackett, A., Cranage, A., Craven, H., Craw, S., Crawford, M., Cutts, T., Dabrowska, M., Davies, M., Dawson, J., Day, C., Densem, A., Dibling, T., Dockree, C., Dodd, D., Dogga, S., Dougherty, M., Dove, A., Drummond, L., Dudek, M., Durrant, L., Easthope, E., Eckert, S., Ellis, P., Farr, B., Fenton, M., Ferrero, M., Flack, N., Fordham, H., Forsythe, G., Francis, M., Fraser, A., Freeman, A., Galvin, A., Garcia-Casado, M., Gedny, A., Girgis, S., Glover, J., Goodwin, S., Gould, O., Gray, A., Gray, E., Griffiths, C., Gu, Y., Guerin, F., Hamilton, W., Hanks, H., Harrison, E., Harrott, A., Harry, E., Harvison, J., Heath, P., Hernandez-Koutoucheva, A., Hobbs, R., Holland, D., Holmes, S., Hornett, G., Hough, N., Huckle, L., Hughes-Hallet, L., Hunter, A., Inglis, S., Iqbal, S., Jackson, A., Jackson, D., Verdejo, C. J., Jones, M., Kallepally, K., Kay, K., Keatley, J., Keith, A., King, A., Kitchin, L., Kleanthous, M., Klimekova, M., Korlevic, P., Krasheninnkova, K., Lane, G., Langford, C., Laverack, A., Law, K., Lensing, S., Lewis-Wade, A., Liddle, J., Lin, Q., Lindsay, S., Linsdell, S., Long, R., Lovell, J., Mack, J., Maddison, M., Makunin, A., Mamun, I., Mansfield, J., Marriott, N., Martin, M., Mayho, M., Mccarthy, S., Mcclintock, J., Mchugh, S., Mcminn, L., Meadows, C., Mobley, E., Moll, R., Morra, M., Morrow, L., Murie, K., Nash, S., Nathwani, C., Naydenova, P., Neaverson, A., Nerou, E., Nicholson, J., Nimz, T., Noell, G. G., O'Meara, S., Ohan, V., Olney, C., Ormond, D., Oszlanczi, A., Pang, Y. F., Pardubska, B., Park, N., Parmar, A., Patel, G., Payne, M., Peacock, S., Petersen, A., Plowman, D., Preston, T., Puethe, C., Quail, M., Rajan, D., Rance, R., Rawlings, S., Redshaw, N., Reynolds, J., Reynolds, M., Rice, S., Richardson, M., Roberts, C., Robinson, K., Robinson, M., Robinson, D., Rogers, H., Rojo, E. M., Roopra, D., Rose, M., Rudd, L., Sadri, R., Salmon, N., Saul, D., Schwach, F., Scott, C., Seekings, P., Shirley, L., Simms, A., Sinnott, M., Sivadasan, S., Siwek, B., Sizer, D., Skeldon, K., Skelton, J., Slater-Tunstill, J., Sloper, L., Smerdon, N., Smith, C., Smith, J., Smith, K., Smith, M., Smith, S., Smith, T., Sneade, L., Soria, C. D., Sousa, C., Souster, E., Sparkes, A., Spencer-Chapman, M., Squares, J., Steed, C., Stickland, T., Still, I., Stratton, M., Strickland, M., Swann, A., Swiatkowska, A., Sycamore, N., Swift, E., Symons, E., Szluha, S., Taluy, E., Tao, N., Taylor, K., Thompson, S., Thompson, M., Thomson, M., Thomson, N., Thurston, S., Toombs, D., Topping, B., Tovar-Corona, J., Ungureanu, D., Uphill, J., Urbanova, J., Jansen Van, P., Vancollie, V., Voak, P., Walker, D., Walker, M., Waller, M., Ward, G., Weatherhogg, C., Webb, N., Wells, A., Wells, E., Westwood, L., Whipp, T., Whiteley, T., Whitton, G., Whitwham, A., Widaa, S., Williams, M., Wilson, M., Wright, S., Farr, B. W., Quail, M. A., Thurston, S. A. J., Bronner, I. F., Redshaw, N. M., Lensing, S. V., Balcazar, C. E., Gallagher, M. D., Williamson, K. A., Stanton, T. D., Michelsen, M. L., Warwick-Dugdale, J., Manley, R., Farbos, A., Harrison, J. W., Sambles, C. M., Studholme, D. J., Lackenby, A., Mbisa, T., Platt, S., Miah, S., Bibby, D., Manso, C., Hubb, J., Dabrera, G., Ramsay, M., Bradshaw, D., Schaefer, U., Groves, N., Gallagher, E., Lee, D., Williams, D., Ellaby, N., Hartman, H., Manesis, N., Patel, V., Ledesma, J., Twohig, K. A., Allara, E., Pearson, C., Cheng, J. K. J., Bridgewater, H. E., Frost, L. R., Taylor-Joyce, G., Brown, P. E., Tong, L., Broos, A., Mair, D., Nichols, J., Carmichael, S. N., Smollett, K. L., Nomikou, K., Aranday-Cortes, E., Johnson, N., Nickbakhsh, S., Vamos, E. E., Hughes, M., Rainbow, L., Eccles, R., Nelson, C., Whitehead, M., Gregory, R., Gemmell, M., Wierzbicki, C., Webster, H. J., Fisher, C. L., Signell, A. W., Betancor, G., Wilson, H. D., Nebbia, G., Flaviani, F., Cerda, A. C., Merrill, T. V., Wilson, R. E., Cotic, M., Bayzid, N., Thompson, T., Acheson, E., Rushton, S., O'Brien, S., Baker, D. J., Rudder, S., Aydin, A., Sang, F., Debebe, J., Francois, S., Vasylyeva, T. I., Zamudio, M. E., Gutierrez, B., Marchbank, A., Maksimovic, J., Spellman, K., Mccluggage, K., Morgan, M., Beer, R., Afifi, S., Workman, T., Fuller, W., Bresner, C., Angyal, A., Green, L. R., Parsons, P. J., Tucker, R. M., Brown, R., Whiteley, M., Rowe, W., Siveroni, I., Le-Viet, T., Gaskin, A., Johnson, R., Sharrocks, K., Blane, E., Modis, Y., Leigh, K. E., Briggs, J. A. G., van Gils, M. J., Smith, K. G. C., Bradley, J. R., Doffinger, R., Ceron-Gutierrez, L., Barcenas-Morales, G., Pollock, D. D., Goldstein, R. A., Smielewska, A., Skittrall, J. P., Gouliouris, T., Goodfellow, I. G., Gkrania-Klotsas, E., Illingworth, C. J. R., Mccoy, L. E., Gupta, R. K., Medical Microbiology and Infection Prevention, AII - Infectious diseases, Collier, Dami A [0000-0001-5446-4423], Jahun, Aminu [0000-0002-4585-1701], Temperton, Nigel [0000-0002-7978-3815], Modis, Yorgo [0000-0002-6084-0429], Briggs, John AG [0000-0003-3990-6910], Goldstein, Richard A [0000-0001-5148-4672], Skittrall, Jordan P [0000-0002-8228-3758], Gkrania-Klotsas, Effrossyni [0000-0002-0930-8330], McCoy, Laura E [0000-0001-9503-7946], Gupta, Ravindra K [0000-0001-9751-1808], and Apollo - University of Cambridge Repository
Subjects: 0301 basic medicine, Male, Time Factors, viruses, Passive, Antibodies, Viral, CITIID-NIHR BioResource COVID-19 Collaboration, 2.1 Biological and endogenous factors, Viral, Aetiology, Neutralizing, Lung, Phylogeny, neutralising antibodies, Infectivity, education.field_of_study, Genome, Multidisciplinary, Alanine, biology, High-Throughput Nucleotide Sequencing, Viral Load, Spike Glycoprotein, Virus Shedding, Adenosine Monophosphate, Aged, Antibodies, Neutralizing, COVID-19, Chronic Disease, Genome, Viral, Humans, Immune Evasion, Immune Tolerance, Immunization, Passive, Immunosuppression Therapy, Mutagenesis, Mutant Proteins, Mutation, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Evolution, Molecular, Infectious Diseases, Pneumonia & Influenza, Antibody, Infection, Viral load, Biotechnology, Evolution, General Science & Technology, antibody escape, Convalescent plasma, 030106 microbiology, Population, evasion, Antibodies, Virus, Article, Vaccine Related, resistance, 03 medical and health sciences, Immune system, COVID-19 Genomics UK (COG-UK) Consortium, Biodefense, Genetics, Viral shedding, education, COVID-19 Serotherapy, QR355, Prevention, Wild type, Molecular, Pneumonia, Virology, COVID-19 Drug Treatment, Coronavirus, Emerging Infectious Diseases, Good Health and Well Being, 030104 developmental biology, biology.protein, Immunization, immune suppression, mutation
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

6. Calicivirus Replication and Reverse Genetics

Author: Goodfellow, I., primary and Taube, S., additional
Published: 2016
Full Text: View/download PDF

7. Contributors

Author: Ajami, N.J., primary, Angel, J., additional, Angel, M., additional, Arias, C.F., additional, Atmar, R.L., additional, Bányai, K., additional, Brandtzaeg, P., additional, Cheung, W., additional, Choi, J.-M., additional, Crawford, S.E., additional, Cunha, J.B., additional, Desselberger, U., additional, Díaz-Salinas, M.A., additional, Dormitzer, P.R., additional, Elftman, M.D., additional, Estes, M.K., additional, Franco, M.A., additional, Garg, R.R., additional, Gaunt, E., additional, Goodfellow, I., additional, Green, K.Y., additional, Greenberg, H.B., additional, Hagbom, M., additional, Hammarström, L., additional, Harrison, S.C., additional, Herrera, D., additional, Isa, P., additional, Kandasamy, S., additional, Kang, G., additional, Karst, S.M., additional, Khamrin, P., additional, Kolawole, A.O., additional, Larson, G., additional, Le Pendu, J., additional, Lever, A., additional, López, S., additional, López, T., additional, Maneekarn, N., additional, Marcotte, H., additional, Marvin, S., additional, Meliopoulos, V.A., additional, Muhaxhiri, Z., additional, Murillo, A., additional, Nasir, W., additional, Navarro, A., additional, Parra, M., additional, Patton, J.T., additional, Petrosino, J.F., additional, Pitzer, V.E., additional, Venkataram Prasad, B.V., additional, Ramani, S., additional, Rydell, G.E., additional, Saif, L.J., additional, Sastri, N.P., additional, Schultz-Cherry, S., additional, Sen, A., additional, Shanker, S., additional, Silva-Ayala, D., additional, Svensson, L., additional, Taube, S., additional, Ushijima, H., additional, Vesikari, T., additional, Vlasova, A.N., additional, Williamson, L., additional, Wobus, C.E., additional, and Zachos, N.C., additional
Published: 2016
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8. Effective control of SARS-CoV-2 transmission between healthcare workers during a period of diminished community prevalence of COVID-19

Author: Jones, N. K., Rivett, L., Sparkes, D., Forrest, S., Sridhar, S., Young, J., Pereira-Dias, J., Cormie, C., Gill, H., Reynolds, N., Wantoch, M., Routledge, M., Warne, B., Levy, J., Jimenez, W. D. C., Samad, F. N. B., Mcnicholas, C., Ferris, M., Gray, J., Gill, M., Curran, M. D., Fuller, S., Chaudhry, A., Shaw, A., Bradley, J. R., Hannon, G. J., Goodfellow, I. G., Dougan, G., Smith, K. G. C., Lehner, P. J., Wright, G., Matheson, N. J., Baker, S., Weekes, M. P., Bradley, J., Goodfellow, I., Gupta, R., Lyons, P. A., Torok, M. E., Toshner, M., Kean, I., Caddy, S., Caller, L., Feltwell, T., Hall, G., Hamilton, W., Hosmillo, M., Houldcroft, C., Jahun, A., Khokhar, F., Meredith, L., Yakovleva, A., Butcher, H., Caputo, D., Clapham-Riley, D., Dolling, H., Furlong, A., Graves, B., Gresley, E. L., Kingston, N., Papadia, S., Stark, H., Stirrups, K. E., Webster, J., Calder, J., Harris, J., Hewitt, S., Kennet, J., Meadows, A., Rastall, R., Brien, C. O., Price, J., Publico, C., Rowlands, J., Ruffolo, V., Tordesillas, H., Hannon, G., Brookes, K., Canna, L., Cruz, I., Dempsey, K., Elmer, A., Escoffery, N., Jones, H., Ribeiro, C., Saunders, C., Wright, A., Nyagumbo, R., Roberts, A., Bucke, A., Hargreaves, S., Johnson, D., Narcorda, A., Read, D., Sparke, C., Worboys, L., Lagadu, K., Mactavous, L., Gould, T., Raine, T., Mather, C., Ramenatte, N., Vallier, A. -L., Kasanicki, M., Eames, P. -J., Thake, L., Bartholomew, N., Brown, N., Curran, M., Parmar, S., Zhang, H., Bowring, A., Martell, G., Quinnell, N., Wright, J., Murphy, H., Dunmore, B. J., Legchenko, E., Graf, S., Huang, C., Hodgson, J., Hunter, K., Martin, J., Mescia, F., Odonnell, C., Pointon, L., Shih, J., Sutcliffe, R., Tilly, T., Tong, Z., Treacy, C., Wood, J., Bergamaschi, L., Betancourt, A., Bowyer, G., De Sa, A., Epping, M., Hinch, A., Huhn, O., Jarvis, I., Lewis, D., Marsden, J., Mccallum, S., Nice, F., Omarjee, O., Perera, M., Romashova, N., Strezlecki, M., Yarkoni, N. S., Turner, L., Bailey, B., Doughton, R., Workman, C., Trotter, C., David, W., Jimenez, C., Jones, Nick K [0000-0003-4475-7761], Sridhar, Sushmita [0000-0001-7453-7482], Hannon, Gregory J [0000-0003-4021-3898], Goodfellow, Ian G [0000-0002-9483-510X], Lehner, Paul J [0000-0001-9383-1054], Matheson, Nicholas J [0000-0002-3318-1851], Weekes, Michael P [0000-0003-3196-5545], and Apollo - University of Cambridge Repository
Subjects: 0301 basic medicine, Male, Infectious Disease Transmission, global health, Occupational safety and health, Hospitals, University, Patient-to-Professional, 0302 clinical medicine, COVID-19 Testing, Patient Admission, Nasopharynx, Pandemic, Epidemiology, Prevalence, Medicine, Infection control, Mass Screening, 030212 general & internal medicine, Viral, Biology (General), Family Characteristics, General Neuroscience, Infectious, human biology, virus diseases, General Medicine, Middle Aged, Hospitals, 3. Good health, virology, Community-Acquired Infections, Occupational Diseases, England, epidemiology, Female, medicine.symptom, Symptom Assessment, Coronavirus Infections, Hospital Units, Adult, medicine.medical_specialty, Infectious Disease Transmission, Patient-to-Professional, QH301-705.5, Health Personnel, infectious disease, Science, Pneumonia, Viral, Real-Time Polymerase Chain Reaction, Asymptomatic, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Betacoronavirus, Disease Transmission, Disease Transmission, Infectious, Humans, human, Human Biology and Medicine, Hospitals, Teaching, Pandemics, Mass screening, Asymptomatic Diseases, emerging pathogens, University, Infection Control, General Immunology and Microbiology, business.industry, Clinical Laboratory Techniques, SARS-CoV-2, Teaching, COVID-19, Pneumonia, medicine, occupational health, Contact Tracing, Program Evaluation, 030104 developmental biology, Epidemiology and Global Health, Emergency medicine, business, Research Advance, Contact tracing
Abstract: Previously, we showed that 3% (31/1032)of asymptomatic healthcare workers (HCWs) from a large teaching hospital in Cambridge, UK, tested positive for SARS-CoV-2 in April 2020. About 15% (26/169) HCWs with symptoms of coronavirus disease 2019 (COVID-19) also tested positive for SARS-CoV-2 (Rivett et al., 2020). Here, we show that the proportion of both asymptomatic and symptomatic HCWs testing positive for SARS-CoV-2 rapidly declined to near-zero between 25th April and 24th May 2020, corresponding to a decline in patient admissions with COVID-19 during the ongoing UK ‘lockdown’. These data demonstrate how infection prevention and control measures including staff testing may help prevent hospitals from becoming independent ‘hubs’ of SARS-CoV-2 transmission, and illustrate how, with appropriate precautions, organizations in other sectors may be able to resume on-site work safely.
Published: 2020

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

Author: Bergamaschi, L., Mescia, F., Turner, L., Hanson, A. L., Kotagiri, P., Dunmore, B. J., Ruffieux, H., de Sa, A., Huhn, O., Morgan, M. D., Gerber, P. P., Wills, M. R., Baker, S., Calero-Nieto, F. J., Doffinger, R., Dougan, G., Elmer, A., Goodfellow, I. G., Gupta, R. K., Hosmillo, M., Hunter, K., Kingston, N., Lehner, P. J., Matheson, N. J., Nicholson, J. K., Petrunkina, A. M., Richardson, S., Saunders, C., Thaventhiran, J. E. D., Toonen, E. J. M., Weekes, M. P., Gottgens, B., Toshner, M., Hess, C., Bradley, J. R., Lyons, P. A., Smith, K. G. C., Allison, J., Ansaripour, A., Betancourt, A., Bong, S. -H., Bower, G., Bucke, A., Bullman, B., Bunclark, K., Butcher, H., Calder, J., Canna, L., Caputo, D., Clapham-Riley, D., Cossetti, C., Coudert, J. D., de Bie, E. M. D. D., Dewhurst, E., di Stefano, G., Domingo, J., Epping, M., Fahey, C., Fawke, S., Fuller, S., Furlong, A., Gleadall, N., Graf, S., Graves, B., Gray, J., Grenfell, R., Harris, J., Hewitt, S., Hinch, A., Hodgson, J., Holmes, E., Huang, C., Ivers, T., Jackson, S., Jarvis, I., Jones, E., Kennet, J., Jose, S., Josipovic, M., Kasanicki, M., Kourampa, J., Laurenti, E., Legchenko, E., Le Gresley, E., Lewis, D., Linger, R., Mackay, M., Marioni, J. C., Marsden, J., Martin, J., Matara, C., Meadows, A., Meloy, S., Mende, N., Michael, A., Michel, R., Mwaura, L., Muldoon, F., Nice, F., O'Brien, C., O'Donnell, C., Okecha, G., Omarjee, O., Ovington, N., Owehand, W. H., Papadia, S., Patterson, C., Perera, M., Phelan, I., Pointon, L., Polgarova, P., Polwarth, G., Pond, N., Price, J., Publico, C., Rastall, R., Ribeiro, C., Richoz, N., Romashova, V., Rossi, S., Rowlands, J., Ruffolo, V., Yarkoni, N. S., Sharma, R., Shih, J., Selvan, M., Spencer, S., Stefanucci, L., Stark, H., Stephens, J., Stirrups, K. E., Strezlecki, M., Summers, C., Sutcliffe, R., Tilly, T., Tong, Z., Tordesillas, H., Treacy, C., Townsend, P., Walker, N., Webster, J., Wilson, N. K., Wood, J., Wylot, M., Yong, C., Mescia, Federica [0000-0002-2759-4027], Hanson, Aimee [0000-0002-0231-8771], Ruffieux, Helene [0000-0002-7113-2540], Morgan, Michael [0000-0003-0757-0711], Wills, Mark [0000-0001-8548-5729], Baker, Stephen [0000-0003-1308-5755], Dougan, Gordon [0000-0003-0022-965X], Gupta, Ravindra [0000-0001-9751-1808], Hosmillo, Myra [0000-0002-3514-7681], Kingston, Nathalie [0000-0002-9190-2231], Lehner, Paul [0000-0001-9383-1054], Matheson, Nicholas [0000-0002-3318-1851], Richardson, Sylvia [0000-0003-1998-492X], Thaventhiran, James [0000-0001-8616-074X], Weekes, Michael [0000-0003-3196-5545], Gottgens, Berthold [0000-0001-6302-5705], Toshner, Mark [0000-0002-3969-6143], Bradley, John [0000-0002-7774-8805], Lyons, Paul [0000-0001-7035-8997], Smith, Kenneth [0000-0003-3829-4326], Apollo - University of Cambridge Repository, and Collaboration, Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource
Subjects: 0301 basic medicine, Pathology, medicine.medical_specialty, Immunology, Disease, macromolecular substances, immune pathology, Biology, CD8-Positive T-Lymphocytes, Systemic inflammation, Lymphocyte Activation, Severity of Illness Index, Article, Oxidative Phosphorylation, 03 medical and health sciences, recovery, 0302 clinical medicine, Immunophenotyping, Immune system, Immunopathology, Bystander effect, medicine, Immunology and Allergy, Humans, complement, Longitudinal Studies, systemic inflammation, bystander CD8+ T cell, SARS-CoV-2, Gene Expression Profiling, Interleukin, COVID-19, interferon, Prognosis, TNF-α, Biomarkers, Cytokines, Disease Susceptibility, Host-Pathogen Interactions, Inflammation Mediators, Phenotype, Reactive Oxygen Species, Transcriptome, 030104 developmental biology, Infectious Diseases, 030220 oncology & carcinogenesis, Tumor necrosis factor alpha, medicine.symptom
Abstract: The kinetics of the immune changes in COVID-19 across severity groups have not been rigorously assessed. Using immunophenotyping, RNA sequencing, and serum cytokine analysis, we analyzed serial samples from 207 SARS-CoV2-infected individuals with a range of disease severities over 12 weeks from symptom onset. An early robust bystander CD8+ T cell immune response, without systemic inflammation, characterized asymptomatic or mild disease. Hospitalized individuals had delayed bystander responses and systemic inflammation that was already evident near symptom onset, indicating that immunopathology may be inevitable in some individuals. Viral load did not correlate with this early pathological response but did correlate with subsequent disease severity. Immune recovery is complex, with profound persistent cellular abnormalities in severe disease correlating with altered inflammatory responses, with signatures associated with increased oxidative phosphorylation replacing those driven by cytokines tumor necrosis factor (TNF) and interleukin (IL)-6. These late immunometabolic and immune defects may have clinical implications., Graphical abstract, The immune changes that underlie COVID-19 severity have not been fully defined. By analyzing a longitudinal cohort of COVID-19 patients and integrating inflammatory factors, immunophenotyping, and transcriptome data, Bergamaschi et al. identify both early and persistent immune changes that distinguish mild and/or asymptomatic from more severe disease.
Published: 2021

10. Pharmacokinetics of TKM-130803 in Ebola virus disease in Sierra Leonean patients

Author: Scott, JT, Sharma, R, Meredith, LW, Dunning, J, Moore, CE, Sahr, F, Ward, S, Goodfellow, I, and Horby, P
Published: 2020
Full Text: View/download PDF

11. Screening of healthcare workers for SARS-CoV-2 highlights the role of asymptomatic carriage in COVID-19 transmission

Author: Rivett, L., Sridhar, S., Sparkes, D., Routledge, M., Jones, N. K., Forrest, S., Young, J., Pereira-Dias, J., Hamilton, W. L., Ferris, M., Torok, M. E., Meredith, L., Curran, M. D., Fuller, S., Chaudhry, A., Shaw, A., Samworth, R. J., Bradley, J. R., Dougan, G., Smith, K. G. C., Lehner, P. J., Matheson, N. J., Wright, G., Goodfellow, I. G., Baker, S., Weekes, M. P., Lyons, P. A., Toshner, M., Warne, B., Scott, J. B., Cormie, C., Gill, H., Kean, I., Maes, M., Reynolds, N., Wantoch, M., Caddy, S., Caller, L., Feltwell, T., Hall, G., Hosmillo, M., Houldcroft, C., Jahun, A., Khokhar, F., Yakovleva, A., Butcher, H., Caputo, D., Clapham-Riley, D., Dolling, H., Furlong, A., Graves, B., Gresley, E. L., Kingston, N., Papadia, S., Stark, H., Stirrups, K. E., Webster, J., Calder, J., Harris, J., Hewitt, S., Kennet, J., Meadows, A., Rastall, R., Brien, C. O., Price, J., Publico, C., Rowlands, J., Ruffolo, V., Tordesillas, H., Brookes, K., Canna, L., Cruz, I., Dempsey, K., Elmer, A., Escoffery, N., Jones, H., Ribeiro, C., Saunders, C., Wright, A., Nyagumbo, R., Roberts, A., Bucke, A., Hargreaves, S., Johnson, D., Narcorda, A., Read, D., Sparke, C., Warboys, L., Lagadu, K., Mactavous, L., Gould, T., Raine, T., Mather, C., Ramenatte, N., Vallier, A. -L., Kasanicki, M., Eames, P. -J., Mcnicholas, C., Thake, L., Bartholomew, N., Brown, N., Parmar, S., Zhang, H., Bowring, A., Martell, G., Quinnell, N., Wright, J., Murphy, H., Dunmore, B. J., Legchenko, E., Graf, S., Huang, C., Hodgson, J., Hunter, K., Martin, J., Mescia, F., O'Donnell, C., Pointon, L., Shih, J., Sutcliffe, R., Tilly, T., Tong, Z., Treacy, C., Wood, J., Bergamaschi, L., Betancourt, A., Bowyer, G., A. D., Sa, Epping, M., Hinch, A., Huhn, O., Jarvis, I., Lewis, D., Marsden, J., Mccallum, S., Nice, F., Rivett, Lucy [0000-0002-2781-9345], Lehner, Paul J [0000-0001-9383-1054], Matheson, Nicholas J [0000-0002-3318-1851], Goodfellow, Ian G [0000-0002-9483-510X], Weekes, Michael P [0000-0003-3196-5545], and Apollo - University of Cambridge Repository
Subjects: 0301 basic medicine, Male, medicine, global health, 0302 clinical medicine, COVID-19 Testing, Epidemiology, Pandemic, Health care, Infection control, 030212 general & internal medicine, Viral, Biology (General), Asymptomatic Infections, Nose, 0303 health sciences, Transmission (medicine), COVID-19, SARS-CoV-2, emerging pathogens, epidemiology, human, human biology, infectious disease, occupational health, virology, virus, Betacoronavirus, COVID-19 Vaccines, Coronavirus Infections, Female, Humans, Infection Control, Pandemics, Pneumonia, Viral, Real-Time Polymerase Chain Reaction, United Kingdom, Clinical Laboratory Techniques, Health Personnel, General Neuroscience, virus diseases, General Medicine, 3. Good health, medicine.anatomical_structure, medicine.symptom, Research Article, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), QH301-705.5, Science, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), education, Asymptomatic, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Internal medicine, Throat, Infectious disease (athletes), Human Biology and Medicine, 030304 developmental biology, General Immunology and Microbiology, business.industry, Pneumonia, 030104 developmental biology, Epidemiology and Global Health, Carriage, business
Abstract: Significant differences exist in the availability of healthcare worker (HCW) SARS-CoV-2 testing between countries, and existing programmes focus on screening symptomatic rather than asymptomatic staff. Over a 3 week period (April 2020), 1032 asymptomatic HCWs were screened for SARS-CoV-2 in a large UK teaching hospital. Symptomatic staff and symptomatic household contacts were additionally tested. Real-time RT-PCR was used to detect viral RNA from a throat+nose self-swab. 3% of HCWs in the asymptomatic screening group tested positive for SARS-CoV-2. 17/30 (57%) were truly asymptomatic/pauci-symptomatic. 12/30 (40%) had experienced symptoms compatible with coronavirus disease 2019 (COVID-19)>7 days prior to testing, most self-isolating, returning well. Clusters of HCW infection were discovered on two independent wards. Viral genome sequencing showed that the majority of HCWs had the dominant lineage B∙1. Our data demonstrates the utility of comprehensive screening of HCWs with minimal or no symptoms. This approach will be critical for protecting patients and hospital staff., eLife digest Patients admitted to NHS hospitals are now routinely screened for SARS-CoV-2 (the virus that causes COVID-19), and isolated from other patients if necessary. Yet healthcare workers, including frontline patient-facing staff such as doctors, nurses and physiotherapists, are only tested and excluded from work if they develop symptoms of the illness. However, there is emerging evidence that many people infected with SARS-CoV-2 never develop significant symptoms: these people will therefore be missed by ‘symptomatic-only’ testing. There is also important data showing that around half of all transmissions of SARS-CoV-2 happen before the infected individual even develops symptoms. This means that much broader testing programs are required to spot people when they are most infectious. Rivett, Sridhar, Sparkes, Routledge et al. set out to determine what proportion of healthcare workers was infected with SARS-CoV-2 while also feeling generally healthy at the time of testing. Over 1,000 staff members at a large UK hospital who felt they were well enough to work, and did not fit the government criteria for COVID-19 infection, were tested. Amongst these, 3% were positive for SARS-CoV-2. On closer questioning, around one in five reported no symptoms, two in five very mild symptoms that they had dismissed as inconsequential, and a further two in five reported COVID-19 symptoms that had stopped more than a week previously. In parallel, healthcare workers with symptoms of COVID-19 (and their household contacts) who were self-isolating were also tested, in order to allow those without the virus to quickly return to work and bolster a stretched workforce. Finally, the rates of infection were examined to probe how the virus could have spread through the hospital and among staff – and in particular, to understand whether rates of infection were greater among staff working in areas devoted to COVID-19 patients. Despite wearing appropriate personal protective equipment, healthcare workers in these areas were almost three times more likely to test positive than those working in areas without COVID-19 patients. However, it is not clear whether this genuinely reflects greater rates of patients passing the infection to staff. Staff may give the virus to each other, or even acquire it at home. Overall, this work implies that hospitals need to be vigilant and introduce broad screening programmes across their workforces. It will be vital to establish such approaches before ‘lockdown’ is fully lifted, so healthcare institutions are prepared for any second peak of infections.
Published: 2020

12. An integrated national scale SARS-CoV-2 genomic surveillance network

Author: Aanensen, DM, Abudahab, K, Adams, A, Afifi, S, Alam, MT, Alderton, A, Alikhan, N-F, Allan, J, Almsaud, M, Alrezaihi, A, Alruwaili, M, Amato, R, Andersson, M, Angyal, A, Aranday-Cortes, E, Ariani, C, Armstrong, SD, Asamaphan, P, Attwood, S, Aydin, A, Badhan, A, Baker, D, Baker, P, Balcazar, CE, Ball, J, Barton, AE, Bashton, M, Baxter, L, Beale, M, Beaver, C, Beckett, A, Beer, R, Beggs, A, Bell, A, Bellis, KL, Bentley, EG, Berriman, M, Betteridge, E, Bibby, D, Bicknell, K, Birchley, A, Black, G, Blane, B, Bloomfield, S, Bolt, F, Bonsall, DG, Bosworth, A, Bourgeois, Y, Boyd, O, Bradshaw, D, Breuer, J, Bridgewater, H, Brooks, T, Broos, A, Brown, JR, Brown, RL, Brunker, K, Bucca, G, Buck, D, Bull, M, Butcher, E, Caddy, SL, Caller, LG, Cambell, S, Carlile, M, Carmichael, S, Carrilero, L, Castellano, S, Chaloner, J, Chand, M, Chapman, MR, Chappell, J, Charles, I, Chauhan, AJ, Chawla, A, Cheng, E, Churcher, CM, Clark, G, Clark, JJ, Collins, J, Colquhoun, R, Connor, TR, Constantinidou, C, Coombes, J, Corden, S, Cottrell, S, Cowell, A, Curran, MD, Curran, T, Dabrera, G, Danesh, J, Darby, AC, De Cesare, M, Martins, LDO, De Silva, TI, Debebe, B, Dervisevic, S, Dewar, RA, Dia, M, Dorman, M, Dougan, G, Dover, L, Downing, F, Drury, E, Du Plessis, L, Dyal, PL, Eccles, R, Edwards, S, Ellaby, N, Elliott, S, Eltringham, G, Elumogo, N, Essex, S, Evans, CM, Evans, J, Nascimento, FF, Fairley, DJ, Farr, B, Feltwell, T, Ferguson, N, Filipe, ADS, Findlay, J, Forrest, LM, Forrest, S, Foulser, L, Francois, S, Fraser, C, Frost, L, Gallagher, E, Gallagher, MD, Garcia-Dorival, I, Gaskin, A, Gatica-Wilcox, B, Gavriil, A, Geidelberg, L, Gemmell, M, Gerada, A, Gifford, L, Gilbert, L, Gilmore, P, Gilroy, R, Girgis, S, Glaysher, S, Golubchik, T, Goncalves, S, Goodfellow, I, Goodwin, S, Graham, C, Graham, L, Grammatopoulos, D, Green, A, Green, LR, Greenaway, J, Gregory, R, Groves, DC, Groves, N, Guest, M, Gunson, R, Haldenby, S, Hall, G, Hamilton, WL, Han, X, Harris, KA, Harrison, EM, Hartley, C, Herrera, C, Hesketh, A, Heyburn, D, Hill, V, Hiscox, JA, Holden, M, Holmes, A, Holmes, N, Holt, GS, Hopes, R, Hosmillo, M, Houldcroft, CJ, Howson-Wells, H, Hubb, J, Hughe, J, Hughes, M, Hutchings, S, Impey, R, Iturriza-Gomara, M, Jackson, A, Jackson, B, Jackson, DK, Jahun, AS, James, K, Jamrozy, D, Jeffries, A, Jesudason, N, John, M, Johnson, J, Johnson, KJ, Johnson, N, Johnston, I, Jones, B, Jones, R, Jones, S, Jorgensen, D, Kane, L, Kay, GL, Kay, S, Keatley, J-P, Keeley, AJ, Khakh, M, Khokhar, FA, Kitchen, C, Knight, B, Kolyva, A, Kraemer, M, Kristiansen, M, Kumziene-Summerhayes, S, Kwiatkowski, D, Lackenby, A, Langford, C, Lawniczak, M, Thanh, L-V, Lee, D, Letchford, L, Li, K, Li, L, Liggett, S, Lindsey, BB, Livett, R, Lloyd, A, Lo, S, Lockhart, M, Loh, J, Loman, NJ, Loose, M, Lucaci, A, Ludden, C, Luu, L, Lyons, RA, MacIntyre-Cockett, G, MacLean, A, Mair, D, Maksimovic, J, Manley, R, Manso, C, Manson, J, Martincorena, I, Masoli, J, Mather, AE, Mbisa, T, McCluggage, K, McClure, P, McCrone, JT, McDonald, S, McHugh, MP, McKenna, JM, McMinn, L, McMurray, C, Meadows, L, Menegazzo, M, Meredith, LW, Merrick, I, Mestek-Boukhibar, L, Miah, S, Michell, S, Michelsen, ML, Molnar, Z, Moore, C, Moore, N, Morgan, M, Morgan, S, Muddyman, D, Muir, DA, Muir, P, Myers, R, Nastouli, E, Naydenova, P, Nelson, A, Nelson, C, Nelson, R, Nicholls, S, Nichols, J, Niebel, M, Niola, P, Nomikou, K, O'Grady, J, O'Toole, AN, O'Toole, E, Olateju, C, Orton, RJ, Osman, H, Ott, S, Pacchiarini, N, Padgett, D, Page, AJ, Palmer, S, Panchbhaya, YN, Pandey, S, Park, N, Parker, MD, Parkhill, J, Parr, YA, Parsons, PJ, Partridge, DG, Patel, M, Patterson, S, Payne, B, Peacock, SJ, Penrice-Randal, R, Perry, M, Platt, S, Poplawski, R, Prakash, R, Prestwood, L, Price, A, Price, JR, Puethe, C, Pybus, O, Pymont, H, Quail, M, Quick, J, Raghwani, J, Ragonnet-Cronin, M, Rahman, S, Rainbow, L, Rajatileka, S, Rambaut, A, Ramsay, M, Randell, PA, Randle, NP, Raviprakash, V, Raza, M, Silva, PR, Rey, S, Richter, A, Robertson, DL, Robinson, TI, Robson, SC, Rooke, S, Rowan, A, Rowe, W, Roy, S, Rudder, S, Ruis, C, Sang, F, Scarlett, G, Schaefer, U, Scott, C, Scott, G, Sethi, D, Shaaban, S, Shah, R, Sharma, P, Shawli, GT, Shepherd, J, Sherriff, N, Shirley, L, Sillitoe, J, Simpson, DA, Singer, JB, Siveroni, I, Smith, C, Smith, CP, Smith, DL, Smith, N, Smith, W, Smith-Palmer, A, Smollett, K, Southgate, J, Spellman, K, Spencer-Chapman, M, Sridhar, S, Stanley, R, Stark, R, Stewart, JP, Stockton, J, Stuart, C, Studholme, D, Swainston, N, Swindells, E, Taha, Y, Tariq, MA, Taylor, B, Taylor, GP, Taylor, S, Taylor-Joyce, G, Tedim, AP, Temperton, B, Templeton, KE, Thomson, EC, Thomson, NM, Thornton, A, Thurston, S, Todd, J, Tong, L, Tonkin-Hill, G, Torok, ME, Trebes, A, Trotter, AJ, Tsoleridis, T, Tucker, RM, Tutill, HJ, Underwood, A, Unnikrishnan, M, Vamos, E, Vasylyeva, T, Vattipally, S, Victoria, A, Vipond, B, Volz, EM, Wain, J, Wang, D, Warwick-Dugdale, J, Wastnedge, E, Watkins, J, Watts, J, Webber, M, Weeks, S, Weldon, D, Whitehead, M, Williams, CA, Williams, C, Williams, D, Williams, R, Williams, TC, Wise, E, Wright, V, Wyles, MD, Wyllie, S, Yakovleva, A, Yasir, M, Yeats, C, Yew, WC, Young, GR, Yu, X, and Zarebski, A
Subjects: Microbiology (medical), Scale (ratio), SARS-CoV-2, viruses, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19, COVID-19 Genomics UK (COG-UK) consortiumcontact@cogconsortium.uk, C500, Genome, Viral, Genomics, Biology, C700, Microbiology, Article, Infectious Diseases, Virology, Humans, Cartography
Abstract: The Coronavirus Disease 2019 (COVID-19) Genomics UK Consortium (COG-UK) was launched in March, 2020, with £20 million support from UK Research and Innovation, the UK Department of Health and Social Care, and Wellcome Trust. The goal of this consortium is to sequence severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for up to 230 000 patients, health-care workers, and other essential workers in the UK with COVID-19, which will help to enable the tracking of SARS-CoV-2 transmission, identify viral mutations, and integrate with health data to assess how the viral genome interacts with cofactors and consequences of COVID-19.
Published: 2020
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13. Imperceptible, Robust, and Targeted Adversarial Examples for Automatic Speech Recognition

Author: Qin, Y., Carlini, N., Goodfellow, I., Garrison Cottrell, and Raffel, C.
Subjects: FOS: Computer and information sciences, Computer Science - Machine Learning, Sound (cs.SD), Statistics - Machine Learning, Audio and Speech Processing (eess.AS), FOS: Electrical engineering, electronic engineering, information engineering, Machine Learning (stat.ML), Computer Science - Sound, Electrical Engineering and Systems Science - Audio and Speech Processing, Machine Learning (cs.LG)
Abstract: Adversarial examples are inputs to machine learning models designed by an adversary to cause an incorrect output. So far, adversarial examples have been studied most extensively in the image domain. In this domain, adversarial examples can be constructed by imperceptibly modifying images to cause misclassification, and are practical in the physical world. In contrast, current targeted adversarial examples applied to speech recognition systems have neither of these properties: humans can easily identify the adversarial perturbations, and they are not effective when played over-the-air. This paper makes advances on both of these fronts. First, we develop effectively imperceptible audio adversarial examples (verified through a human study) by leveraging the psychoacoustic principle of auditory masking, while retaining 100% targeted success rate on arbitrary full-sentence targets. Next, we make progress towards physical-world over-the-air audio adversarial examples by constructing perturbations which remain effective even after applying realistic simulated environmental distortions., Comment: International Conference on Machine Learning (ICML), 2019
Published: 2019
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14. A domain agnostic measure for monitoring and evaluating GANs

Author: Grnarova, P., Levy, K. Y., Aurelien Lucchi, Perraudin, N., Goodfellow, I., Hofmann, T., and Krause, A.
Subjects: FOS: Computer and information sciences, Computer Science - Machine Learning, Statistics - Machine Learning, Machine Learning (stat.ML), Machine Learning (cs.LG)
Abstract: Generative Adversarial Networks (GANs) have shown remarkable results in modeling complex distributions, but their evaluation remains an unsettled issue. Evaluations are essential for: (i) relative assessment of different models and (ii) monitoring the progress of a single model throughout training. The latter cannot be determined by simply inspecting the generator and discriminator loss curves as they behave non-intuitively. We leverage the notion of duality gap from game theory to propose a measure that addresses both (i) and (ii) at a low computational cost. Extensive experiments show the effectiveness of this measure to rank different GAN models and capture the typical GAN failure scenarios, including mode collapse and non-convergent behaviours. This evaluation metric also provides meaningful monitoring on the progression of the loss during training. It highly correlates with FID on natural image datasets, and with domain specific scores for text, sound and cosmology data where FID is not directly suitable. In particular, our proposed metric requires no labels or a pretrained classifier, making it domain agnostic.
Published: 2018

15. Targeting macrophage and intestinal epithelial cell specific microRNAs against norovirus restricts replication in vivo

Author: Thorne, L, Lu, J, Chaudhry, Y, Bailey, D, and Goodfellow, I
Subjects: viruses, Macrophages, Norovirus, Epithelial Cells, Virus Replication, Antiviral Agents, Article, Cell Line, Rodent Diseases, Mice, MicroRNAs, Viral Tropism, Disease Transmission, Infectious, Animals, Caliciviridae Infections
Abstract: Until recently, our understanding of the cellular tropism of human norovirus (HuNoV), a major cause of viral gastroenteritis, has been limited. Immune cells and intestinal epithelial cells (IECs) have been proposed as targets of HuNoV replication in vivo, although the contribution of each to pathogenesis and transmission is unknown. Murine norovirus (MNV) is widely used as a surrogate model for HuNoV, as it replicates in cultured immune cells. The importance of the complete MNV immune cell tropism in vivo has not been determined. Recent work has linked replication in IECs to viral persistence in vivo. MNV provides a model to assess the relative contribution of each cell tropism to viral replication in immunocompetent native hosts. Here we exploited cell-specific microRNAs to control MNV replication, through insertion of microRNA target sequences into the MNV genome. We demonstrated the utility of this approach for MNV in vitro by selectively reducing replication in microglial cells, using microglial-specific miR-467c. We then showed that inserting a target sequence for the haematopoietic-specific miR-142-3p abrogated replication in a macrophage cell line. The presence of a target sequence for either miR-142-3p or IEC miR-215 significantly reduced viral secretion during the early stages of a persistent infection in immunocompetent mice, confirming that both cell types support viral replication in vivo. This study provides additional evidence that MNV shares the IEC tropism of HuNoVs in vivo, and now provides a model to dissect the contribution of replication in each cell type to viral pathogenesis and transmission in a native host.
Published: 2018

16. Activation of COX-2/PGE2 Promotes Sapovirus Replication via the Inhibition of Nitric Oxide Production

Author: Alfajaro, MM, Choi, J-S, Kim, D-S, Seo, J-Y, Kim, J-Y, Park, J-G, Soliman, M, Baek, Y-B, Cho, E-H, Kwon, J, Kwon, H-J, Park, S-J, Lee, WS, Kang, M-I, Hosmillo, M, Goodfellow, I, Cho, K-O, Hosmillo, Myra [0000-0002-3514-7681], Goodfellow, Ian [0000-0002-9483-510X], and Apollo - University of Cambridge Repository
Subjects: prostaglandin E2, Cyclooxygenase 2 Inhibitors, Swine, Gene Expression, Nitric Oxide, Virus Replication, Dinoprostone, Sapovirus, Cell Line, Bile Acids and Salts, caliciviruses, cyclooxygenases, Cyclooxygenase 2, Cyclooxygenase 1, Animals, RNA Interference, RNA, Small Interfering, Cells, Cultured, Caliciviridae Infections, Signal Transduction
Abstract: Enteric caliciviruses in the genera Norovirus and Sapovirus are important pathogens that cause severe acute gastroenteritis in both humans and animals. Cyclooxygenases (COXs) and their final product, prostaglandin E2 (PGE2), are known to play important roles in the modulation of both the host response to infection and the replicative cycles of several viruses. However, the precise mechanism(s) by which the COX/PGE2 pathway regulates sapovirus replication remains largely unknown. In this study, infection with porcine sapovirus (PSaV) strain Cowden, the only cultivable virus within the genus Sapovirus, markedly increased COX-2 mRNA and protein levels at 24 and 36 h postinfection (hpi), with only a transient increase in COX-1 levels seen at 24 hpi. The treatment of cells with pharmacological inhibitors, such as nonsteroidal anti-inflammatory drugs or small interfering RNAs (siRNAs) against COX-1 and COX-2, significantly reduced PGE2 production, as well as PSaV replication. Expression of the viral proteins VPg and ProPol was associated with activation of the COX/PGE2 pathway. We observed that pharmacological inhibition of COX-2 dramatically increased NO production, causing a reduction in PSaV replication that could be restored by inhibition of nitric oxide synthase via the inhibitor N-nitro-l-methyl-arginine ester. This study identified a pivotal role for the COX/PGE2 pathway in the regulation of NO production during the sapovirus life cycle, providing new insights into the life cycle of this poorly characterized family of viruses. Our findings also reveal potential new targets for treatment of sapovirus infection. IMPORTANCE: Sapoviruses are among the major etiological agents of acute gastroenteritis in both humans and animals, but little is known about sapovirus host factor requirements. Here, using only cultivable porcine sapovirus (PSaV) strain Cowden, we demonstrate that PSaV induced the vitalization of the cyclooxygenase (COX) and prostaglandin E2 (PGE2) pathway. Targeting of COX-1/2 using nonsteroidal anti-inflammatory drugs (NSAIDs) such as the COX-1/2 inhibitor indomethacin and the COX-2-specific inhibitors NS-398 and celecoxib or siRNAs targeting COXs, inhibited PSaV replication. Expression of the viral proteins VPg and ProPol was associated with activation of the COX/PGE2 pathway. We further demonstrate that the production of PGE2 provides a protective effect against the antiviral effector mechanism of nitric oxide. Our findings uncover a new mechanism by which PSaV manipulates the host cell to provide an environment suitable for efficient viral growth, which in turn can be a new target for treatment of sapovirus infection.
Published: 2017

17. Chapter 3.2 - Calicivirus Replication and Reverse Genetics

Author: Goodfellow, I. and Taube, S.
Published: 2016
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18. Virus genomes reveal factors that spread and sustained the Ebola epidemic

Author: Dudas, G. (Gytis), Carvalho, L.M. (Luiz Max), Bedford, T. (Trevor), Tatem, A.J. (Andrew J.), Baele, G. (Guy), Faria, R. (Rui), Park, D.J. (Daniel J.), Ladner, J.T. (Jason T.), Arias, A., Asogun, D. (Danny), Bielejec, F. (Filip), Caddy, S.L., Cotten, M. (Matthew), D'Ambrozio, J. (Jonathan), Dellicour, S. (Simon), Di Caro, A. (Antonino), Diclaro, J.W. (Joseph W.), Duraffour, S. (Sophie), Elmore, M.J. (Michael J.), Fakoli, L.S. (Lawrence S.), Faye, O. (Ousmane), Gilbert, M.L. (Merle L.), Gevao, S.M. (Sahr M.), Gire, S. (Stephen), Gladden-Young, A. (Adrianne), Gnirke, A. (Andreas), Goba, A. (Augustine), Grant, D.S. (Donald S.), Haagmans, B.L. (Bart), Hiscox, J.A. (Julian A.), Jah, U., Kugelman, J.R. (Jeffrey R.), Liu, D. (Di), Lu, J. (Jia), Malboeuf, C.M. (Christine M.), Mate, S. (Suzanne), Matthews, D.A. (David A.), Matranga, C.B. (Christian B.), Meredith, L.W. (Luke W.), Qu, J. (James), Quick, J. (Joshua), Pas, S.D. (Suzan), Phan, M.V.T. (My V. T.), Pollakis, G. (G.), Reusken, C.B.E.M. (Chantal), Sanchez-Lockhart, M. (Mariano), Schaffner, S.F. (Stephen F.), Schieffelin, J.S. (John S.), Sealfon, R.S. (Rachel S.), Simon-Loriere, E. (Etienne), Smits, S.L. (Saskia), Stoecker, K. (Kilian), Thorne, L. (Lucy), Tobin, E.A. (Ekaete Alice), Vandi, M.A. (Mohamed A.), Watson, S.J. (Simon J.), West, K. (Kendra), Whitmer, S. (Shannon), Wiley, M.R. (Michael R.), Winnicki, S.M. (Sarah M.), Wohl, S. (Shirlee), Wölfel, R. (Roman), Yozwiak, N.L. (Nathan L.), Andersen, K.G. (Kristian G.), Blyden, S.O. (Sylvia O.), Bolay, F. (Fatorma), Carroll, M.W. (Miles W.), Dahn, B. (Bernice), Diallo, B. (Boubacar), Formenty, P. (Pierre), Fraser, C. (Christophe), Gao, G.F. (George F.), Garry, R.F. (Robert F.), Goodfellow, I. (Ian), Günther, S. (Stephan), Happi, C.T. (Christian T.), Holmes, E.C. (Edward C.), Kargbo, B. (Brima), Keïta, S. (Sakoba), Kellam, P. (Paul), Koopmans D.V.M., M.P.G. (Marion), Kuhn, J.H. (Jens H.), Loman, N.J. (Nicholas J.), Magassouba, N. (N'Faly), Naidoo, D. (Dhamari), Nichol, S.T. (Stuart T.), Nyenswah, T. (Tolbert), Palacios, G. (Gustavo), Pybus, O. (Oliver), Sabeti, P.C. (Pardis C.), Sall, A. (Amadou), Ströher, U. (Ute), Wurie, I., Suchard, M.A. (Marc), Lemey, P. (Philippe), Rambaut, A. (Andrew), Dudas, G. (Gytis), Carvalho, L.M. (Luiz Max), Bedford, T. (Trevor), Tatem, A.J. (Andrew J.), Baele, G. (Guy), Faria, R. (Rui), Park, D.J. (Daniel J.), Ladner, J.T. (Jason T.), Arias, A., Asogun, D. (Danny), Bielejec, F. (Filip), Caddy, S.L., Cotten, M. (Matthew), D'Ambrozio, J. (Jonathan), Dellicour, S. (Simon), Di Caro, A. (Antonino), Diclaro, J.W. (Joseph W.), Duraffour, S. (Sophie), Elmore, M.J. (Michael J.), Fakoli, L.S. (Lawrence S.), Faye, O. (Ousmane), Gilbert, M.L. (Merle L.), Gevao, S.M. (Sahr M.), Gire, S. (Stephen), Gladden-Young, A. (Adrianne), Gnirke, A. (Andreas), Goba, A. (Augustine), Grant, D.S. (Donald S.), Haagmans, B.L. (Bart), Hiscox, J.A. (Julian A.), Jah, U., Kugelman, J.R. (Jeffrey R.), Liu, D. (Di), Lu, J. (Jia), Malboeuf, C.M. (Christine M.), Mate, S. (Suzanne), Matthews, D.A. (David A.), Matranga, C.B. (Christian B.), Meredith, L.W. (Luke W.), Qu, J. (James), Quick, J. (Joshua), Pas, S.D. (Suzan), Phan, M.V.T. (My V. T.), Pollakis, G. (G.), Reusken, C.B.E.M. (Chantal), Sanchez-Lockhart, M. (Mariano), Schaffner, S.F. (Stephen F.), Schieffelin, J.S. (John S.), Sealfon, R.S. (Rachel S.), Simon-Loriere, E. (Etienne), Smits, S.L. (Saskia), Stoecker, K. (Kilian), Thorne, L. (Lucy), Tobin, E.A. (Ekaete Alice), Vandi, M.A. (Mohamed A.), Watson, S.J. (Simon J.), West, K. (Kendra), Whitmer, S. (Shannon), Wiley, M.R. (Michael R.), Winnicki, S.M. (Sarah M.), Wohl, S. (Shirlee), Wölfel, R. (Roman), Yozwiak, N.L. (Nathan L.), Andersen, K.G. (Kristian G.), Blyden, S.O. (Sylvia O.), Bolay, F. (Fatorma), Carroll, M.W. (Miles W.), Dahn, B. (Bernice), Diallo, B. (Boubacar), Formenty, P. (Pierre), Fraser, C. (Christophe), Gao, G.F. (George F.), Garry, R.F. (Robert F.), Goodfellow, I. (Ian), Günther, S. (Stephan), Happi, C.T. (Christian T.), Holmes, E.C. (Edward C.), Kargbo, B. (Brima), Keïta, S. (Sakoba), Kellam, P. (Paul), Koopmans D.V.M., M.P.G. (Marion), Kuhn, J.H. (Jens H.), Loman, N.J. (Nicholas J.), Magassouba, N. (N'Faly), Naidoo, D. (Dhamari), Nichol, S.T. (Stuart T.), Nyenswah, T. (Tolbert), Palacios, G. (Gustavo), Pybus, O. (Oliver), Sabeti, P.C. (Pardis C.), Sall, A. (Amadou), Ströher, U. (Ute), Wurie, I., Suchard, M.A. (Marc), Lemey, P. (Philippe), and Rambaut, A. (Andrew)
Abstract: The 2013-2016 West African epidemic caused by the Ebola virus was of unprecedented magnitude, duration and impact. Here we reconstruct the dispersal, proliferation and decline of Ebola virus throughout the region by analysing 1,610 Ebola virus genomes, which represent over 5% of the known cases. We test the association of geography, climate and demography with viral movement among administrative regions, inferring a classic 'gravity' model, with intense dispersal between larger and closer populations. Despite attenuation of international dispersal after border closures, cross-border transmission had already sown the seeds for an international epidemic, rendering these measures ineffective at curbing the epidemic. We address why the epidemic did not spread into neighbouring countries, showing that these countries were susceptible to substantial outbreaks but at lower risk of introductions. Finally, we reveal that this large epidemic was a heterogeneous and spatially dissociated collection of transmission clusters of varying size, duration and connectivity. These insights will help to inform interventions in future epidemics.
Published: 2017
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19. Neurodevelopmental protein Musashi-1 interacts with the Zika genome and promotes viral replication

Author: Chavali, P.L., Stojic, L., Meredith, L.W., Joseph, N., Nahorski, M.S., Sanford, T.J., Sweeney, T.R., Krishna, B.A., Hosmillo, M., Firth, A.E., Bayliss, R., Marcelis, C.L.M., Lindsay, S., Goodfellow, I., Woods, C.G., Gergely, F., Chavali, P.L., Stojic, L., Meredith, L.W., Joseph, N., Nahorski, M.S., Sanford, T.J., Sweeney, T.R., Krishna, B.A., Hosmillo, M., Firth, A.E., Bayliss, R., Marcelis, C.L.M., Lindsay, S., Goodfellow, I., Woods, C.G., and Gergely, F.
Abstract: Item does not contain fulltext, A recent outbreak of Zika virus in Brazil has led to a simultaneous increase in reports of neonatal microcephaly. Zika targets cerebral neural precursors, a cell population essential for cortical development, but the cause of this neurotropism remains obscure. Here we report that the neural RNA-binding protein Musashi-1 (MSI1) interacts with the Zika genome and enables viral replication. Zika infection disrupts the binding of MSI1 to its endogenous targets, thereby deregulating expression of factors implicated in neural stem cell function. We further show that MSI1 is highly expressed in neural progenitors of the human embryonic brain and is mutated in individuals with autosomal recessive primary microcephaly. Selective MSI1 expression in neural precursors could therefore explain the exceptional vulnerability of these cells to Zika infection.
Published: 2017

20. Virus genomes reveal the factors that spread and sustained the West African Ebola epidemic

Author: Dudas, G, Carvalho, LM, Bedford, T, Tatem, A, Baele, G, Faria, N, Park, D, Ladner, J, Arias, A, Asogun, D, Bielejec, F, Caddy, S, Cotten, M, Dambrozio, J, Dellicour, S, Di Caro, A, Diclaro, J, Duraffour, S, Elmore, M, Fakoli, L, Gilbert, M, Gevao, S, Gire, S, Gladden-Young, A, Gnirke, A, Goba, A, Grant, D, Haagmans, B, Hiscox, J, Jah, U, Kargbo, B, Kugelman, J, Liu, D, Lu, J, Malboeuf, C, Mate, S, Matthews, D, Matranga, C, Meredith, L, Qu, J, Quick, J, Pas, S, Phan, MVT, Poliakis, G, Reusken, C, Sanchez-Lockhart, M, Schaffner, S, Schieffelin, J, Sealfon, R, Simon-Loriere, E, Smits, S, Stoecker, K, Thorne, L, Tobin, E, Vandi, M, Watson, S, West, K, Whitmer, S, Wiley, M, Winnicki, S, Wohl, S, Wölfel, R, Yozwiak, N, Andersen, K, Blyden, S, Bolay, F, Carroll, M, Dahn, B, Diallo, B, Formenty, P, Fraser, C, Gao, G, Garry, R, Goodfellow, I, Günther, S, Happi, C, Holmes, E, Kellam, P, Koopmans, MPG, Loman, N, Magassouba, N, Naidoo, D, Nichol, S, Nyenswah, T, Palacios, G, Pybus, O, Sabeti, P, Sall, A, Sakoba, K, Ströeher, U, Wurie, I, Suchard, M, Lemey, P, Rambaut, A, and Wellcome Trust
Subjects: viruses
Abstract: Summary The 2013-2016 epidemic of Ebola virus disease in West Africa was of unprecedented magnitude, duration and impact. Extensive collaborative sequencing projects have produced a large collection of over 1600 Ebola virus genomes, representing over 5% of known cases, unmatched for any single human epidemic. In this comprehensive analysis of this entire dataset, we reconstruct in detail the history of migration, proliferation and decline of Ebola virus throughout the region. We test the association of geography, climate, administrative boundaries, demography and culture with viral movement among 56 administrative regions. Our results show that during the outbreak viral lineages moved according to a classic ‘gravity’ model, with more intense migration between larger and more proximate population centers. Notably, we find that despite a strong attenuation of international dispersal after border closures, localized cross-border transmission beforehand had already set the seeds for an international epidemic, rendering these measures relatively ineffective in curbing the epidemic. We use this empirical evidence to address why the epidemic did not spread into neighboring countries, showing that although these regions were susceptible to developing significant outbreaks, they were also at lower risk of viral introductions. Finally, viral genome sequence data uniquely reveals this large epidemic to be a heterogeneous and spatially dissociated collection of transmission clusters of varying size, duration and connectivity. These insights will help inform approaches to intervention in such epidemics in the future.
Published: 2016

21. Ebola virus disease cluster — Northern Sierra Leone, January 2016

Author: Alpren, C., Sloan, M., Boegler, K. A., Martin, D. W., Ervin, E., Washburn, F., Rickert, R., Singh, T., Redd, J. T., Bangalie, A., Bass, M., Bennett, S. D., Boateng, I. A., Campbell, D., Cassell, C., Cotton, M., Duffy, N., Goodfellow, I., Hersey, S., Jackson, E. L., Jah, U., Jimissa, A. S., Kamara, A. S., Kamara, F., Kellam, P., Levine, R., Luke Meredith, Miller, L. A., Moody-Geissler, S., Musoke, R., Naidoo, D., Ndyahikayo, J., Njie, G., Phan, M., Rambaut, A., and Sesay, F.
Subjects: Health Information Management, Epidemiology, Health, Toxicology and Mutagenesis, Health(social science)
Published: 2016
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22. The RNA Helicase eIF4A is required for Sapovirus translation

Author: Hosmillo, M, Sweeney, TR, Chaudhry, Y, Leen, E, Curry, S, Goodfellow, I, Cho, K-O, Sweeney, Trevor [0000-0003-4016-7326], Goodfellow, Ian [0000-0002-9483-510X], Apollo - University of Cambridge Repository, and Biotechnology and Biological Sciences Research Council (BBSRC)
Subjects: VPG, Science & Technology, Reticulocytes, Swine, 11 Medical And Health Sciences, Genome, Viral, 06 Biological Sciences, Virus Replication, Sapovirus, INITIATION, Sterols, Viral Proteins, Virology, BINDING, Eukaryotic Initiation Factor-4A, Mutation, Animals, RNA, Viral, MESSENGER-RNAS, 07 Agricultural And Veterinary Sciences, Rabbits, 5' Untranslated Regions, Life Sciences & Biomedicine, PORCINE ENTERIC CALICIVIRUS, Protein Binding
Abstract: The eukaryotic initiation factor (eIF) 4A is a DEAD-box helicase that unwinds RNA structure in the 5´-untranslated region (UTR) of mRNAs. Here, we investigated the role of eIF4A in porcine sapovirus VPg-dependent translation. Using inhibitors and dominant negative mutants, we found that eIF4A is required for viral translation and infectivity, suggesting that despite the presence of a very short 5´-UTR, eIF4A is required to unwind RNA structure in the sapovirus genome to facilitate virus translation.
Published: 2016

23. Evidence for human norovirus infection of dogs in the UK

Author: Caddy, S L, De Rougemont, A, Emmott, E, El-Attar, L M R, Mitchell, J A, Hollinshead, M, Belliot, G, Brownlie, J, Le Pendu, J, and Goodfellow, I
Abstract: Human noroviruses (HuNoVs) are a major cause of viral gastroenteritis, with an estimated 3 million cases per year in the United Kingdom. HuNoVs have recently been isolated from pet dogs in Europe (M. Summa, C.-H. von Bonsdorff, and L. Maunula, J Clin Virol 53:244–247, 2012, http://dx.doi.org/10.1016/j.jcv.2011.12.014), raising concerns about potential zoonotic infections. With 31% of United Kingdom households owning a dog, this could prove to be an important transmission route. To examine this risk, canine tissues were studied for their ability to bind to HuNoV in vitro. In addition, canine stool samples were analyzed for the presence of viral nucleic acid, and canine serum samples were tested for the presence of anti-HuNoV antibodies. The results showed that seven different genotypes of HuNoV virus-like particles (VLPs) can bind to canine gastrointestinal tissue, suggesting that infection is at least theoretically possible. Although HuNoV RNA was not identified in stool samples from 248 dogs, serological evidence of previous exposure to HuNoV was obtained in 43/325 canine serum samples. Remarkably, canine seroprevalence for different HuNoV genotypes mirrored the seroprevalence in the human population. Though entry and replication within cells have not been demonstrated, the canine serological data indicate that dogs produce an immune response to HuNoV, implying productive infection. In conclusion, this study reveals zoonotic implications for HuNoV, and to elucidate the significance of this finding, further epidemiological and molecular investigations will be essential.
Published: 2015

24. Experimental Treatment of Ebola Virus Disease with TKM-130803: A Single-Arm Phase 2 Clinical Trial

Author: von Seidlein, L, Dunning, J, Sahr, F, Rojek, A, Gannon, F, Carson, G, Idriss, B, Massaquoi, T, Gandi, R, Joseph, S, Osman, HK, Brooks, TJG, Simpson, AJH, Goodfellow, I, Thorne, L, Arias, A, Merson, L, Castle, L, Howell-Jones, R, Pardinaz-Solis, R, Hope-Gill, B, Ferri, M, Grove, J, Kowalski, M, Stepniewska, K, Lang, T, Whitehead, J, Olliaro, P, Samai, M, Horby, PW, von Seidlein, L, Dunning, J, Sahr, F, Rojek, A, Gannon, F, Carson, G, Idriss, B, Massaquoi, T, Gandi, R, Joseph, S, Osman, HK, Brooks, TJG, Simpson, AJH, Goodfellow, I, Thorne, L, Arias, A, Merson, L, Castle, L, Howell-Jones, R, Pardinaz-Solis, R, Hope-Gill, B, Ferri, M, Grove, J, Kowalski, M, Stepniewska, K, Lang, T, Whitehead, J, Olliaro, P, Samai, M, and Horby, PW
Abstract: BACKGROUND: TKM-130803, a small interfering RNA lipid nanoparticle product, has been developed for the treatment of Ebola virus disease (EVD), but its efficacy and safety in humans has not been evaluated. METHODS AND FINDINGS: In this single-arm phase 2 trial, adults with laboratory-confirmed EVD received 0.3 mg/kg of TKM-130803 by intravenous infusion once daily for up to 7 d. On days when trial enrolment capacity was reached, patients were enrolled into a concurrent observational cohort. The primary outcome was survival to day 14 after admission, excluding patients who died within 48 h of admission. After 14 adults with EVD had received TKM-130803, the pre-specified futility boundary was reached, indicating a probability of survival to day 14 of ≤0.55, and enrolment was stopped. Pre-treatment geometric mean Ebola virus load in the 14 TKM-130803 recipients was 2.24 × 109 RNA copies/ml plasma (95% CI 7.52 × 108, 6.66 × 109). Two of the TKM-130803 recipients died within 48 h of admission and were therefore excluded from the primary outcome analysis. Of the remaining 12 TKM-130803 recipients, nine died and three survived. The probability that a TKM-130803 recipient who survived for 48 h will subsequently survive to day 14 was estimated to be 0.27 (95% CI 0.06, 0.58). TKM-130803 infusions were well tolerated, with 56 doses administered and only one possible infusion-related reaction observed. Three patients were enrolled in the observational cohort, of whom two died. CONCLUSIONS: Administration of TKM-130803 at a dose of 0.3 mg/kg/d by intravenous infusion to adult patients with severe EVD was not shown to improve survival when compared to historic controls. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201501000997429.
Published: 2016

25. Laboratory support during and after the Ebola virus endgame: Towards a sustained laboratory infrastructure

Author: Goodfellow, I., Reusken, C.B.E.M. (Chantal), Koopmans D.V.M., M.P.G. (Marion), Goodfellow, I., Reusken, C.B.E.M. (Chantal), and Koopmans D.V.M., M.P.G. (Marion)
Abstract: The Ebola virus epidemic in West Africa is on the brink of entering a second phase in which the (inter)national efforts to slow down virus transmission will be engaged to end the epidemic. The response community must consider the longevity of their current laboratory support, as it is essential that diagnostic capacity in the affected countries be supported beyond the end of the epidemic. The emergency laboratory response should be used to support building structural diagnostic and outbreak surveillance capacity.
Published: 2015

26. Genotypic anomaly in ebola virus strains circulating in magazine wharf Area, Freetown, Sierra Leone, 2015

Author: Smits, S.L. (Saskia), Pas, S.D. (Suzan), Reusken, C.B.E.M. (Chantal), Haagmans, B.L. (Bart), Pertile, P., Cancedda, C., Dierberg, K., Wurie, I., Kamara, A., Kargbo, D., Caddy, S.L., Arias, A., Thorne, L., Lu, J., Jah, U., Goodfellow, I., Koopmans D.V.M., M.P.G. (Marion), Smits, S.L. (Saskia), Pas, S.D. (Suzan), Reusken, C.B.E.M. (Chantal), Haagmans, B.L. (Bart), Pertile, P., Cancedda, C., Dierberg, K., Wurie, I., Kamara, A., Kargbo, D., Caddy, S.L., Arias, A., Thorne, L., Lu, J., Jah, U., Goodfellow, I., and Koopmans D.V.M., M.P.G. (Marion)
Abstract: The Magazine Wharf area, Freetown, Sierra Leone was a focus of ongoing Ebola virus transmission from late June 2015. Viral genomes linked to this area contain a series of 13 T to C substitutions in a 150 base pair intergenic region downstream of viral protein 40 open reading frame, similar to the Ebolavirus/H.sapienswt/ SLE/2014/Makona-J0169 strain (J0169) detected in the same town in November 2014. This suggests that recently circulating viruses from Freetown descend from a J0169-like virus.
Published: 2015
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27. Genotypic anomaly in Ebola virus strains circulating in Magazine Wharf area, Freetown, Sierra Leone, 2015

Author: Smits, Saskia, Pas, Suzan, Reusken, Chantal, Haagmans, Bart, Pertile, P, Cancedda, C, Dierberg, K, Wurie, I, Kamara, A, Kargbo, D, Caddy, SL, Arias, A, Thorne, L, Lu, J, Jah, U, Goodfellow, I, Koopmans, Marion, Smits, Saskia, Pas, Suzan, Reusken, Chantal, Haagmans, Bart, Pertile, P, Cancedda, C, Dierberg, K, Wurie, I, Kamara, A, Kargbo, D, Caddy, SL, Arias, A, Thorne, L, Lu, J, Jah, U, Goodfellow, I, and Koopmans, Marion
Abstract: The Magazine Wharf area, Freetown, Sierra Leone was a focus of ongoing Ebola virus transmission from late June 2015. Viral genomes linked to this area contain a series of 13 T to C substitutions in a 150 base pair intergenic region downstream of viral protein 40 open reading frame, similar to the Ebolavirus/H. sapienswt/SLE/2014/Makona-J0169 strain (J0169) detected in the same town in November 2014. This suggests that recently circulating viruses from Freetown descend from a J0169-like virus.
Published: 2015

28. Hepatitis E in southern Vietnam: Seroepidemiology in humans and molecular epidemiology in pigs.

Author: Berto, A., Pham, H. A., Thao, T. T. N., Vy, N. H. T., Caddy, S. L., Hiraide, R., Tue, N. T., Goodfellow, I., Carrique‐Mas, J. J., Thwaites, G. E., Baker, S., Boni, M. F., and the VIZIONS consortium
Subjects: HEPATITIS E virus, SEROPREVALENCE, ZOONOSES, MOLECULAR epidemiology, DISEASE risk factors
Abstract: Summary: Viral pathogens account for a significant proportion of the burden of emerging infectious diseases in humans. The Wellcome Trust‐Vietnamese Initiative on Zoonotic Infections (WT‐VIZIONS) is aiming to understand the circulation of viral zoonotic pathogens in animals that pose a potential risk to human health. Evidence suggests that human exposure and infections with hepatitis E virus (HEV) genotypes (GT) 3 and 4 results from zoonotic transmission. Hypothesising that HEV GT3 and GT4 are circulating in the Vietnamese pig population and can be transmitted to humans, we aimed to estimate the seroprevalence of HEV exposure in a population of farmers and the general population. We additionally performed sequence analysis of HEV in pig populations in the same region to address knowledge gaps regarding HEV circulation and to evaluate if pigs were a potential source of HEV exposure. We found a high prevalence of HEV GT3 viral RNA in pigs (19.1% in faecal samples and 8.2% in rectal swabs) and a high HEV seroprevalence in pig farmers (16.0%) and a hospital‐attending population (31.7%) in southern Vietnam. The hospital population was recruited as a general‐population proxy even though this particular population subgroup may introduce bias. The detection of HEV RNA in pigs indicates that HEV may be a zoonotic disease risk in this location, although a larger sample size is required to infer an association between HEV positivity in pigs and seroprevalence in humans. [ABSTRACT FROM AUTHOR]
Published: 2018
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29. Laboratory support during and after the Ebola virus endgame: towards a sustained laboratory infrastructure

Author: Goodfellow, I, primary, Reusken, C, additional, and Koopmans, M, additional
Published: 2015
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30. Genotypic anomaly in Ebola virus strains circulating in Magazine Wharf area, Freetown, Sierra Leone, 2015.

Author: Smits, S. L., Pas, S. D., Reusken, C. B., Haagmans, B. L., Pertile, P., Cancedda, C., Dierberg, K., Wurie, I., Kamara, A., Kargbo, D., Caddy, S. L., Arias, A., Thorne, L., Lu, J., Jah, U., Goodfellow, I., and Koopmans, M. P.
Published: 2015
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31. Nitazoxanide Is an Ineffective Treatment of Chronic Norovirus in Patients With X-Linked Agammaglobulinemia and May Yield False-Negative Polymerase Chain Reaction Findings in Stool Specimens.

Author: Kempf, Bjoern, Edgar, J. David, Mc Caughey, Conall, Devlin, Lisa A., Thorne, L., and Goodfellow, I.
Subjects: AGAMMAGLOBULINEMIA, ANTIVIRAL agents, X-linked genetic disorders, GENETIC mutation, POLYMERASE chain reaction, RNA viruses, THIAZOLES, NOROVIRUS diseases
Published: 2017
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32. Letters.

Author: Booth, Peter, Goodfellow, I., Sparkes, Tom, Hayes, Geoff, and Mann, S.
Subjects: CYCLISTS, CYCLING
Abstract: Several letters to the editor are presented, including a letter in response to the obituary for cyclist Roy Manser in the August 20, 2015 issue, a letter in which the sender talks about the brilliant performance of cyclist Lizzie Armistead, and a letter in which the sender laments the composition of Team Sky cycling team.
Published: 2015

33. Filtration of viral aerosols via a hybrid carbon nanotube active filter

Author: Brian Graves, Myra Hosmillo, Jeronimo Terrones, Michael Glerum, Ian Goodfellow, Liron Issman, Shuki Yeshurun, Martin Pick, Adam M. Boies, Rulan Qiao, James A. Elliott, Issman, L [0000-0002-9804-3724], Graves, B [0000-0002-5282-5253], Goodfellow, I [0000-0002-9483-510X], and Apollo - University of Cambridge Repository
Subjects: Multi-functional materials, Materials science, Air changes per hour, Carbon nanotubes, General Chemistry, Carbon nanotube, law.invention, Filter (aquarium), Air-filtration, Membrane, Chemical engineering, law, HEPA, General Materials Science, Bio-aerosols, Active filter, Filtration, Air filter, Anti-Viral
Abstract: Exposure to expired particles and droplets carrying infectious viruses is a primary transmission pathway for respiratory diseases. Removal of particles and droplets via filtration from a volume can drastically reduce the exposure to viruses, but viruses may remain active on filtration surfaces as potential resuspension or fomite risks. Here, we report the development of macroscopic carbon nanotube air filters synthesized using ultra-thin carbon nanotube electrically conductive membranes, mechanically supported by a porous polyester backing. Filtration efficiencies were measured up to 99.999%, while ultra-thin materials with low areal density (0.1 g m─2) exhibited pressure drops comparable to commercial High-Efficiency Particulate Air (HEPA) filters. These electrically conductive filters are actively self-sanitized by thermal flashes via resistive heating to temperatures above 80 °C within seconds or less. Such temperatures were proven to achieve full deactivation of a betacoronavirus and an adeno-associated virus retained on filter surfaces. A filtration unit prototype equipped with a CNT filter module (∼1.2 m2) was shown to achieve air purification of 99% of a room within 10 min at 26 air changes per hour.
Published: 2021
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34. Genome sequences of antimicrobial-resistant Campylobacter coli and Campylobacter jejuni , isolated from poultry in Ukraine.

Author: Halka I, Shchur N, Bortz E, Mandyhra S, Nedosekov V, Katsaraba O, Goodfellow I, Drown DM, and Kovalenko G
Abstract: Genomes of a Campylobacter coli OR12-like strain ChP2023 (1,713,995 bp) isolated from broiler chicken and Campylobacter jejuni subsp. jejuni NCTC 11168R-like strain KF2023 (1,729,995 bp) isolated from turkey, from poultry production facilities in Ukraine in 2023, were sequenced using Oxford Nanopore Technologies. Both genomes included antibiotic resistance genes and other virulence factors., Competing Interests: E.B. has consulted for B&V, Metabiota, and Epidemic Biosciences, LLC, on unrelated projects. The other authors declare no conflict of interest.
Published: 2024
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35. Patterns of the within-host evolution of human norovirus in immunocompromised individuals and implications for treatment.

Author: Izquierdo-Lara RW, Villabruna N, Hesselink DA, Schapendonk CME, Ribó Pons S, Nieuwenhuijse D, Meier JIJ, Goodfellow I, Dalm VASH, Fraaij PLA, van Kampen JJA, Koopmans MPG, and de Graaf M
Subjects: Humans, Evolution, Molecular, Phylogeny, Genetic Variation, Mutation, Male, Female, Norovirus genetics, Norovirus immunology, Immunocompromised Host, Caliciviridae Infections immunology, Caliciviridae Infections virology, Caliciviridae Infections therapy, Capsid Proteins genetics, Capsid Proteins immunology, High-Throughput Nucleotide Sequencing
Abstract: Background: Currently, there is no licensed treatment for chronic norovirus infections, but the use of intra-duodenally-delivered immunoglobulins is promising; nevertheless, varying results have limited their wide use. Little is known about the relationship between norovirus genetic diversity and treatment efficacy., Methods: We analyzed the norovirus within-host diversity and evolution in a cohort of 20 immunocompromised individuals using next-generation sequencing (NGS) and clone-based sequencing of the capsid (VP1) gene. Representative VP1s were expressed and their glycan receptor binding affinity and antigenicity were evaluated., Findings: The P2 domain, within the VP1, accumulated up to 30-fold more non-synonymous mutations than other genomic regions. Intra-host virus populations in these patients tended to evolve into divergent lineages that were often antigenically distinct. Several of these viruses were widely resistant to binding-blocking antibodies in immunoglobulin preparations. Notably, for one patient, a single amino-acid substitution in the P2 domain resulted in an immune-escape phenotype, and it was likely the main contributor to treatment failure. Furthermore, we found evidence for transmission of late-stage viruses between two immunocompromised individuals., Interpretation: The findings demonstrated that within-host noroviruses in chronic infections tend to evolve into antigenically distinct subpopulations. This antigenic evolution was likely caused by the remaining low immunity levels exerted by immunocompromised individuals, possibly undermining antiviral treatment. Our observations provide insights into norovirus (within-host) evolution and treatment., Funding: Erasmus MC grant mRACE, the European Union's Horizon 2020 research and innovation program under grant agreement No. 874735 (VEO), and the NWO STEVIN award (Koopmans)., Competing Interests: Declaration of interests D.A. Hesselink has received grant support, lecture and consulting fees from Astellas Pharma and Chiesi Pharma (paid to his institution). D.A. Hesselink does not have employment or stock ownership at any of these companies, and neither does he have patents nor patent applications. V.A.S.H. Dalm has received lecture and consulting fees from Pharming, CSL Behring, Takeda, GSK. He has received grant support from Takeda, CSL Behring, AstraZeneca, Moderna and Pharming NV (paid to institution). V.A.S.H. Dalm does not have employment or stock ownership at any of these or other companies, neither does he have patents or patent applications. P.L.A. Fraaij has received grant support from the Erasmus University Rotterdam, TU Delft, ZonMW (Netherlands) and the European Union's Horizon 2020 program (paid to institution). These institutions did not have any role in the development of this project. I. Goodfellow has received grant support from the Wellcome trust. This institution did not have any role in the development of this project. All other authors report no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Published: 2024
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36. Zika viruses encode 5' upstream open reading frames affecting infection of human brain cells.

Author: Lefèvre C, Cook GM, Dinan AM, Torii S, Stewart H, Gibbons G, Nicholson AS, Echavarría-Consuegra L, Meredith LW, Lulla V, McGovern N, Kenyon JC, Goodfellow I, Deane JE, Graham SC, Lakatos A, Lambrechts L, Brierley I, and Irigoyen N
Subjects: Humans, Animals, Virus Replication, Organoids virology, Chlorocebus aethiops, Viral Tropism, Vero Cells, Mosquito Vectors virology, Ribosomes metabolism, Zika Virus genetics, Zika Virus physiology, Open Reading Frames genetics, Zika Virus Infection virology, Brain virology, Neurons virology, Neurons metabolism
Abstract: Zika virus (ZIKV), an emerging mosquito-borne flavivirus, is associated with congenital neurological complications. Here, we investigate potential pathological correlates of virus gene expression in representative ZIKV strains through RNA sequencing and ribosome profiling. In addition to the single long polyprotein found in all flaviviruses, we identify the translation of unrecognised upstream open reading frames (uORFs) in the genomic 5' region. In Asian/American strains, ribosomes translate uORF1 and uORF2, whereas in African strains, the two uORFs are fused into one (African uORF). We use reverse genetics to examine the impact on ZIKV fitness of different uORFs mutant viruses. We find that expression of the African uORF and the Asian/American uORF1 modulates virus growth and tropism in human cortical neurons and cerebral organoids, suggesting a potential role in neurotropism. Although the uORFs are expressed in mosquito cells, we do not see a measurable effect on transmission by the mosquito vector in vivo. The discovery of ZIKV uORFs sheds new light on the infection of the human brain cells by this virus and raises the question of their existence in other neurotropic flaviviruses., (© 2024. The Author(s).)
Published: 2024
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37. Author Correction: Subtle adversarial image manipulations influence both human and machine perception.

Author: Veerabadran V, Goldman J, Shankar S, Cheung B, Papernot N, Kurakin A, Goodfellow I, Shlens J, Sohl-Dickstein J, Mozer MC, and Elsayed GF
Published: 2024
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38. Subtle adversarial image manipulations influence both human and machine perception.

Author: Veerabadran V, Goldman J, Shankar S, Cheung B, Papernot N, Kurakin A, Goodfellow I, Shlens J, Sohl-Dickstein J, Mozer MC, and Elsayed GF
Subjects: Humans, Perception, Neural Networks, Computer, Brain diagnostic imaging
Abstract: Although artificial neural networks (ANNs) were inspired by the brain, ANNs exhibit a brittleness not generally observed in human perception. One shortcoming of ANNs is their susceptibility to adversarial perturbations-subtle modulations of natural images that result in changes to classification decisions, such as confidently mislabelling an image of an elephant, initially classified correctly, as a clock. In contrast, a human observer might well dismiss the perturbations as an innocuous imaging artifact. This phenomenon may point to a fundamental difference between human and machine perception, but it drives one to ask whether human sensitivity to adversarial perturbations might be revealed with appropriate behavioral measures. Here, we find that adversarial perturbations that fool ANNs similarly bias human choice. We further show that the effect is more likely driven by higher-order statistics of natural images to which both humans and ANNs are sensitive, rather than by the detailed architecture of the ANN., (© 2023. Springer Nature Limited.)
Published: 2023
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39. Hepatitis C Virus in people with experience of injection drug use following their displacement to Southern Ukraine before 2020.

Author: Yakovleva A, Kovalenko G, Redlinger M, Smyrnov P, Tymets O, Korobchuk A, Kotlyk L, Kolodiazieva A, Podolina A, Cherniavska S, Antonenko P, Strathdee SA, Friedman SR, Goodfellow I, Wertheim JO, Bortz E, Meredith L, and Vasylyeva TI
Subjects: Humans, Hepacivirus genetics, Ukraine epidemiology, Cross-Sectional Studies, Phylogeny, Seroepidemiologic Studies, Bayes Theorem, Prevalence, HIV Infections complications, Substance Abuse, Intravenous complications, Substance Abuse, Intravenous epidemiology, Hepatitis C
Abstract: Background: Due to practical challenges associated with genetic sequencing in low-resource environments, the burden of hepatitis C virus (HCV) in forcibly displaced people is understudied. We examined the use of field applicable HCV sequencing methods and phylogenetic analysis to determine HCV transmission dynamics in internally displaced people who inject drugs (IDPWID) in Ukraine., Methods: In this cross-sectional study, we used modified respondent-driven sampling to recruit IDPWID who were displaced to Odesa, Ukraine, before 2020. We generated partial and near full length genome (NFLG) HCV sequences using Oxford Nanopore Technology (ONT) MinION in a simulated field environment. Maximum likelihood and Bayesian methods were used to establish phylodynamic relationships., Results: Between June and September 2020, we collected epidemiological data and whole blood samples from 164 IDPWID (PNAS Nexus.2023;2(3):pgad008). Rapid testing (Wondfo® One Step HCV; Wondfo® One Step HIV1/2) identified an anti-HCV seroprevalence of 67.7%, and 31.1% of participants tested positive for both anti-HCV and HIV. We generated 57 partial or NFLG HCV sequences and identified eight transmission clusters, of which at least two originated within a year and a half post-displacement., Conclusions: Locally generated genomic data and phylogenetic analysis in rapidly changing low-resource environments, such as those faced by forcibly displaced people, can help inform effective public health strategies. For example, evidence of HCV transmission clusters originating soon after displacement highlights the importance of implementing urgent preventive interventions in ongoing situations of forced displacement., (© 2023. The Author(s).)
Published: 2023
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40. Human influenza A virus H1N1 in marine mammals in California, 2019.

Author: Plancarte M, Kovalenko G, Baldassano J, Ramírez AL, Carrillo S, Duignan PJ, Goodfellow I, Bortz E, Dutta J, van Bakel H, and Coffey LL
Subjects: Animals, Humans, California epidemiology, Influenza A Virus, H1N1 Subtype, Caniformia, Influenza A virus, Seals, Earless, Influenza, Human epidemiology
Abstract: From 2011-2018, we conducted surveillance in marine mammals along the California coast for influenza A virus (IAV), frequently detecting anti-influenza antibodies and intermittently detecting IAV. In spring 2019, this pattern changed. Despite no change in surveillance intensity, we detected IAV RNA in 10 samples in March and April, mostly in nasal and rectal swabs from northern elephant seals (Mirounga angustirostris). Although virus isolation was unsuccessful, IAV sequenced from one northern elephant seal nasal swab showed close genetic identity with pandemic H1N1 IAV subclade 6B.1A.1 that was concurrently circulating in humans in the 2018/19 influenza season. This represents the first report of human A(H1N1)pdm09 IAV in northern elephant seals since 2010, suggesting IAV continues to spill over from humans to pinnipeds., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Plancarte et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Published: 2023
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41. From a genome-wide screen of RNAi molecules against SARS-CoV-2 to a validated broad-spectrum and potent prophylaxis.

Author: Yogev O, Weissbrod O, Battistoni G, Bressan D, Naamati A, Falciatori I, Berkyurek AC, Rasnic R, Izuagbe R, Hosmillo M, Ilan S, Grossman I, McCormick L, Honeycutt CC, Johnston T, Gagne M, Douek DC, Goodfellow I, Hannon GJ, and Erlich Y
Subjects: Animals, Cricetinae, Administration, Intranasal, Mesocricetus, RNA Interference, COVID-19 prevention & control, RNA, Small Interfering genetics, RNA, Small Interfering therapeutic use, SARS-CoV-2 genetics
Abstract: Expanding the arsenal of prophylactic approaches against SARS-CoV-2 is of utmost importance, specifically those strategies that are resistant to antigenic drift in Spike. Here, we conducted a screen of over 16,000 RNAi triggers against the SARS-CoV-2 genome, using a massively parallel assay to identify hyper-potent siRNAs. We selected Ten candidates for in vitro validation and found five siRNAs that exhibited hyper-potent activity (IC50 < 20 pM) and strong blockade of infectivity in live-virus experiments. We further enhanced this activity by combinatorial pairing of the siRNA candidates and identified cocktails that were active against multiple types of variants of concern (VOC). We then examined over 2,000 possible mutations in the siRNA target sites by using saturation mutagenesis and confirmed broad protection of the leading cocktail against future variants. Finally, we demonstrated that intranasal administration of this siRNA cocktail effectively attenuates clinical signs and viral measures of disease in the gold-standard Syrian hamster model. Our results pave the way for the development of an additional layer of antiviral prophylaxis that is orthogonal to vaccines and monoclonal antibodies., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Published: 2023
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42. Author Correction: Tracking SARS-COV-2 variants using Nanopore sequencing in Ukraine in 2021.

Author: Yakovleva A, Kovalenko G, Redlinger M, Liulchuk MG, Bortz E, Zadorozhna VI, Scherbinska AM, Wertheim JO, Goodfellow I, Meredith L, and Vasylyeva TI
Published: 2023
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43. Phylodynamics and migration data help describe HIV transmission dynamics in internally displaced people who inject drugs in Ukraine.

Author: Kovalenko G, Yakovleva A, Smyrnov P, Redlinger M, Tymets O, Korobchuk A, Kolodiazieva A, Podolina A, Cherniavska S, Skaathun B, Smith LR, Strathdee SA, Wertheim JO, Friedman SR, Bortz E, Goodfellow I, Meredith L, and Vasylyeva TI
Abstract: Internally displaced persons are often excluded from HIV molecular epidemiology surveillance due to structural, behavioral, and social barriers in access to treatment. We test a field-based molecular epidemiology framework to study HIV transmission dynamics in a hard-to-reach and highly stigmatized group, internally displaced people who inject drugs (IDPWIDs). We inform the framework by Nanopore generated HIV pol sequences and IDPWID migration history. In June-September 2020, we recruited 164 IDPWID in Odesa, Ukraine, and obtained 34 HIV sequences from HIV-infected participants. We aligned them to publicly available sequences ( N = 359) from Odesa and IDPWID regions of origin and identified 7 phylogenetic clusters with at least 1 IDPWID. Using times to the most recent common ancestors of the identified clusters and times of IDPWID relocation to Odesa, we infer potential post-displacement transmission window when infections likely to happen to be between 10 and 21 months, not exceeding 4 years. Phylogeographic analysis of the sequence data shows that local people in Odesa disproportionally transmit HIV to the IDPWID community. Rapid transmissions post-displacement in the IDPWID community might be associated with slow progression along the HIV continuum of care: only 63% of IDPWID were aware of their status, 40% of those were in antiviral treatment, and 43% of those were virally suppressed. Such HIV molecular epidemiology investigations are feasible in transient and hard-to-reach communities and can help indicate best times for HIV preventive interventions. Our findings highlight the need to rapidly integrate Ukrainian IDPWID into prevention and treatment services following the dramatic escalation of the war in 2022., (© The Author(s) 2023. Published by Oxford University Press on behalf of National Academy of Sciences.)
Published: 2023
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44. Genomics-informed outbreak investigations of SARS-CoV-2 using civet.

Author: O'Toole Á, Hill V, Jackson B, Dewar R, Sahadeo N, Colquhoun R, Rooke S, McCrone JT, Duggan K, McHugh MP, Nicholls SM, Poplawski R, Aanensen D, Holden M, Connor T, Loman N, Goodfellow I, Carrington CVF, Templeton K, and Rambaut A
Abstract: The scale of data produced during the SARS-CoV-2 pandemic has been unprecedented, with more than 13 million sequences shared publicly at the time of writing. This wealth of sequence data provides important context for interpreting local outbreaks. However, placing sequences of interest into national and international context is difficult given the size of the global dataset. Often outbreak investigations and genomic surveillance efforts require running similar analyses again and again on the latest dataset and producing reports. We developed civet (cluster investigation and virus epidemiology tool) to aid these routine analyses and facilitate virus outbreak investigation and surveillance. Civet can place sequences of interest in the local context of background diversity, resolving the query into different 'catchments' and presenting the phylogenetic results alongside metadata in an interactive, distributable report. Civet can be used on a fine scale for clinical outbreak investigation, for local surveillance and cluster discovery, and to routinely summarise the virus diversity circulating on a national level. Civet reports have helped researchers and public health bodies feedback genomic information in the appropriate context within a timeframe that is useful for public health., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 O’Toole et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Published: 2022
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45. Demographic, behavioural and occupational risk factors associated with SARS-CoV-2 infection in UK healthcare workers: a retrospective observational study.

Author: Cooper DJ, Lear S, Sithole N, Shaw A, Stark H, Ferris M, Bradley J, Maxwell P, Goodfellow I, Weekes MP, Seaman S, and Baker S
Subjects: Humans, Retrospective Studies, Health Personnel, Risk Factors, Antibodies, Viral, United Kingdom epidemiology, Demography, SARS-CoV-2, COVID-19 epidemiology
Abstract: 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<0.0001) and being of black ethnicity (6.21 (95% CI 2.69 to 14.3); p<0.0001). Occupational factors associated with a higher risk of seropositivity included working as a physiotherapist (OR 2.78 (95% CI 1.21 to 6.36); p=0.015) and working predominantly in acute medicine (OR 2.72 (95% CI 1.57 to 4.69); p<0.0001) or medical subspecialties (not including infectious diseases) (OR 2.33 (95% CI 1.4 to 3.88); p=0.001). Reporting that adequate personal protective equipment (PPE) was 'rarely' available had an OR of 2.83 (95% CI 1.29 to 6.25; p=0.01). Reporting attending a handover where social distancing was not possible had an OR of 1.39 (95% CI 1.02 to 1.9; p=0.038)., Conclusions: The emergence of SARS-CoV-2 variants and potential vaccine escape continue to threaten stability of healthcare systems worldwide, and sustained vigilance against HCW infection remains a priority. Enhanced risk assessments should be considered for HCWs of black ethnicity, physiotherapists and those working in acute medicine or medical subspecialties. Workplace risk reduction measures include ongoing access to high-quality PPE and effective social distancing measures., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)
Published: 2022
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46. 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 DJ, Lear S, Watson L, Shaw A, Ferris M, Doffinger R, Bousfield R, Sharrocks K, Weekes MP, Warne B, Sparkes D, Jones NK, Rivett L, Routledge M, Chaudhry A, Dempsey K, Matson M, Lakha A, Gathercole G, O'Connor O, Wilson E, Shahzad O, Toms K, Thompson R, Halsall I, Halsall D, Houghton S, Papadia S, Kingston N, Stirrups KE, Graves B, Townsend P, Walker N, Stark H, De Angelis D, Seaman S, Dougan G, Bradley JR, Török ME, Goodfellow I, and Baker S
Subjects: Antibodies, Viral, Health Personnel, Hospitals, Teaching, Humans, Prospective Studies, Risk Factors, Seroepidemiologic Studies, United Kingdom epidemiology, COVID-19 epidemiology, SARS-CoV-2
Abstract: Objectives: To describe the risk factors for SARS-CoV-2 infection in UK healthcare workers (HCWs)., Methods: We conducted a prospective sero-epidemiological study of HCWs at a major UK teaching hospital using a SARS-CoV-2 immunoassay. Risk factors for seropositivity were analysed using multivariate logistic regression., Results: 410/5,698 (7·2%) staff tested positive for SARS-CoV-2 antibodies. Seroprevalence was higher in those working in designated COVID-19 areas compared with other areas (9·47% versus 6·16%) Healthcare assistants (aOR 2·06 [95%CI 1·14-3·71]; p=0·016) and domestic and portering staff (aOR 3·45 [95% CI 1·07-11·42]; p=0·039) had significantly higher seroprevalence than other staff groups after adjusting for age, sex, ethnicity and COVID-19 working location. Staff working in acute medicine and medical sub-specialities were also at higher risk (aOR 2·07 [95% CI 1·31-3·25]; p<0·002). Staff from Black, Asian and minority ethnic (BAME) backgrounds had an aOR of 1·65 (95% CI 1·32 - 2·07; p<0·001) compared to white staff; this increased risk was independent of COVID-19 area working. The only symptoms significantly associated with seropositivity in a multivariable model were loss of sense of taste or smell, fever, and myalgia; 31% of staff testing positive reported no prior symptoms., Conclusions: Risk of SARS-CoV-2 infection amongst HCWs is highly heterogeneous and influenced by COVID-19 working location, role, age and ethnicity. Increased risk amongst BAME staff cannot be accounted for solely by occupational factors., Competing Interests: Competing interests The authors declare that they have no competing interests, (Copyright © 2022. Published by Elsevier Ltd.)
Published: 2022
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47. Tracking SARS-COV-2 variants using Nanopore sequencing in Ukraine in 2021.

Author: Yakovleva A, Kovalenko G, Redlinger M, Liulchuk MG, Bortz E, Zadorozhna VI, Scherbinska AM, Wertheim JO, Goodfellow I, Meredith L, and Vasylyeva TI
Subjects: Humans, SARS-CoV-2 genetics, Ukraine epidemiology, COVID-19 epidemiology, Nanopore Sequencing
Abstract: The use of real-time genomic epidemiology has enabled the tracking of the global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), informing evidence-based public health decision making. Ukraine has experienced four waves of the Coronavirus Disease 2019 (COVID-19) between spring 2020 and spring 2022. However, insufficient capacity for local genetic sequencing limited the potential application of SARS-CoV-2 genomic surveillance for public health response in the country. Herein, we report local sequencing of 103 SARS-CoV-2 genomes from patient samples collected in Kyiv in July-December 2021 using Oxford Nanopore technology. Together with other published Ukrainian SARS-CoV-2 genomes, our data suggest that the third wave of the epidemic in Ukraine (June-December 2021) was dominated by the Delta Variant of Concern (VOC). Our phylogeographic analysis revealed that in summer 2021 Delta VOC was introduced into Ukraine from multiple locations worldwide, with most introductions coming from Central and Eastern European countries. The wide geographic range of Delta introductions coincides with increased volume of travel to Ukraine particularly from locations outside of Europe in summer 2021. This study highlights the need to urgently integrate affordable and easily scaled pathogen sequencing technologies in locations with less developed genomic infrastructure, in order to support local public health decision making., (© 2022. The Author(s).)
Published: 2022
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48. The origins and molecular evolution of SARS-CoV-2 lineage B.1.1.7 in the UK.

Author: Hill V, Du Plessis L, Peacock TP, Aggarwal D, Colquhoun R, Carabelli AM, Ellaby N, Gallagher E, Groves N, Jackson B, McCrone JT, O'Toole Á, Price A, Sanderson T, Scher E, Southgate J, Volz E, Barclay WS, Barrett JC, Chand M, Connor T, Goodfellow I, Gupta RK, Harrison EM, Loman N, Myers R, Robertson DL, Pybus OG, and Rambaut A
Abstract: The first SARS-CoV-2 variant of concern (VOC) to be designated was lineage B.1.1.7, later labelled by the World Health Organization as Alpha. Originating in early autumn but discovered in December 2020, it spread rapidly and caused large waves of infections worldwide. The Alpha variant is notable for being defined by a long ancestral phylogenetic branch with an increased evolutionary rate, along which only two sequences have been sampled. Alpha genomes comprise a well-supported monophyletic clade within which the evolutionary rate is typical of SARS-CoV-2. The Alpha epidemic continued to grow despite the continued restrictions on social mixing across the UK and the imposition of new restrictions, in particular, the English national lockdown in November 2020. While these interventions succeeded in reducing the absolute number of cases, the impact of these non-pharmaceutical interventions was predominantly to drive the decline of the SARS-CoV-2 lineages that preceded Alpha. We investigate the only two sampled sequences that fall on the branch ancestral to Alpha. We find that one is likely to be a true intermediate sequence, providing information about the order of mutational events that led to Alpha. We explore alternate hypotheses that can explain how Alpha acquired a large number of mutations yet remained largely unobserved in a region of high genomic surveillance: an under-sampled geographical location, a non-human animal population, or a chronically infected individual. We conclude that the latter provides the best explanation of the observed behaviour and dynamics of the variant, although the individual need not be immunocompromised, as persistently infected immunocompetent hosts also display a higher within-host rate of evolution. Finally, we compare the ancestral branches and mutation profiles of other VOCs and find that Delta appears to be an outlier both in terms of the genomic locations of its defining mutations and a lack of the rapid evolutionary rate on its ancestral branch. As new variants, such as Omicron, continue to evolve (potentially through similar mechanisms), it remains important to investigate the origins of other variants to identify ways to potentially disrupt their evolution and emergence., (© The Author(s) 2022. Published by Oxford University Press.)
Published: 2022
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49. TRIM7 Restricts Coxsackievirus and Norovirus Infection by Detecting the C-Terminal Glutamine Generated by 3C Protease Processing.

Author: Luptak J, Mallery DL, Jahun AS, Albecka A, Clift D, Ather O, Slodkowicz G, Goodfellow I, and James LC
Subjects: 3C Viral Proteases, Enterovirus, Humans, Norovirus, Viral Proteins genetics, Caliciviridae Infections, Glutamine, Tripartite Motif Proteins genetics, Ubiquitin-Protein Ligases metabolism
Abstract: TRIM7 catalyzes the ubiquitination of multiple substrates with unrelated biological functions. This cross-reactivity is at odds with the specificity usually displayed by enzymes, including ubiquitin ligases. Here we show that TRIM7's extreme substrate promiscuity is due to a highly unusual binding mechanism, in which the PRYSPRY domain captures any ligand with a C-terminal helix that terminates in a hydrophobic residue followed by a glutamine. Many of the non-structural proteins found in RNA viruses contain C-terminal glutamines as a result of polyprotein cleavage by 3C protease. This viral processing strategy generates novel substrates for TRIM7 and explains its ability to inhibit Coxsackie virus and norovirus replication. In addition to viral proteins, cellular proteins such as glycogenin have evolved C-termini that make them a TRIM7 substrate. The 'helix-ΦQ' degron motif recognized by TRIM7 is reminiscent of the N-end degron system and is found in ~1% of cellular proteins. These features, together with TRIM7's restricted tissue expression and lack of immune regulation, suggest that viral restriction may not be its physiological function.
Published: 2022
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50. SARS-COV-2 vaccine responses in renal patient populations.

Author: Smith RM, Cooper DJ, Doffinger R, Stacey H, Al-Mohammad A, Goodfellow I, Baker S, Lear S, Hosmilo M, Pritchard N, Torpey N, Jayne D, Yiu V, Chalisey A, Lee J, Vilnar E, Cheung CK, and Jones RB
Subjects: BNT162 Vaccine, COVID-19 Vaccines, Humans, Mycophenolic Acid, Renal Dialysis, Rituximab, SARS-CoV-2, Autoimmune Diseases, COVID-19 prevention & control, Viral Vaccines
Abstract: Background: Dialysis patients and immunosuppressed renal patients are at increased risk of COVID-19 and were excluded from vaccine trials. We conducted a prospective multicentre study to assess SARS-CoV-2 vaccine antibody responses in dialysis patients and renal transplant recipients, and patients receiving immunosuppression for autoimmune disease., Methods: Patients were recruited from three UK centres (ethics:20/EM/0180) and compared to healthy controls (ethics:17/EE/0025). SARS-CoV-2 IgG antibodies to spike protein were measured using a multiplex Luminex assay, after first and second doses of Pfizer BioNTech BNT162b2(Pfizer) or Oxford-AstraZeneca ChAdOx1nCoV-19(AZ) vaccine., Results: Six hundred ninety-two patients were included (260 dialysis, 209 transplant, 223 autoimmune disease (prior rituximab 128(57%)) and 144 healthy controls. 299(43%) patients received Pfizer vaccine and 379(55%) received AZ. Following two vaccine doses, positive responses occurred in 96% dialysis, 52% transplant, 70% autoimmune patients and 100% of healthy controls. In dialysis patients, higher antibody responses were observed with the Pfizer vaccination. Predictors of poor antibody response were triple immunosuppression (adjusted odds ratio [aOR]0.016;95%CI0.002-0.13;p < 0.001) and mycophenolate mofetil (MMF) (aOR0.2;95%CI 0.1-0.42;p < 0.001) in transplant patients; rituximab within 12 months in autoimmune patients (aOR0.29;95%CI 0.008-0.096;p < 0.001) and patients receiving immunosuppression with eGFR 15-29 ml/min (aOR0.031;95%CI 0.11-0.84;p = 0.021). Lower antibody responses were associated with a higher chance of a breakthrough infection., Conclusions: Amongst dialysis, kidney transplant and autoimmune populations SARS-CoV-2 vaccine antibody responses are reduced compared to healthy controls. A reduced response to vaccination was associated with rituximab, MMF, triple immunosuppression CKD stage 4. Vaccine responses increased after the second dose, suggesting low-responder groups should be prioritised for repeated vaccination. Greater antibody responses were observed with the mRNA Pfizer vaccine compared to adenovirus AZ vaccine in dialysis patients suggesting that Pfizer SARS-CoV-2 vaccine should be the preferred vaccine choice in this sub-group., (© 2022. The Author(s).)
Published: 2022
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