Recurrent emergence of SARS-CoV-2 spike deletion H69/V70 and its role in the Alpha variant B.1.1.7
Bo Meng(University of Cambridge), Steven A. Kemp(University of Cambridge), Guido Papa(MRC Laboratory of Molecular Biology), Rawlings Datir(University of Cambridge), Isabella A.T.M. Ferreira(University of Cambridge), Sara Marelli(University of Cambridge), William T. Harvey(MRC University of Glasgow Centre for Virus Research), Spyros Lytras(MRC University of Glasgow Centre for Virus Research), Ahmed Mohamed(The Pirbright Institute), Giulia Gallo(The Pirbright Institute), Nazia Thakur(The Pirbright Institute), Dami A. Collier(University of Cambridge), Petra Mlčochová(University of Cambridge), Samuel C. Robson, Nicholas J. Loman, Thomas R. Connor, Tanya Golubchik, Rocio T. Martinez Nunez, Catherine Ludden, Sally Corden, Ian Johnston(VIR Biotechnology (United States)), David Bonsall(MRC University of Glasgow Centre for Virus Research), Colin P. Smith, Ali Raza Awan, Giselda Bucca, M. Estée Török, Kordo Saeed, Jacqui Prieto, David K. Jackson, William L. Hamilton, Luke B. Snell, Catherine Moore, Ewan M. Harrison, Sónia Gonçalves, Derek Fairley, Matthew Loose, Joanne Watkins, Rich Livett, Samuel Moses, Roberto Amato, Samuel M. Nicholls, Matthew Bull, Darren Smith, Jeff Barrett, David M. Aanensen, Martin D. Curran, Surendra Parmar, Dinesh Aggarwal, James G. Shepherd, Matthew D. Parker, Sharon Glaysher, Matthew Bashton, Anthony P. Underwood, Nicole Pacchiarini, Katie F. Loveson, Kate Templeton, Cordelia F. Langford, John Sillitoe, Thushan I. de Silva, Dennis Wang, Dominic Kwiatkowski, Andrew Rambaut(National University of Singapore), Justin O’Grady, Simon Cottrell, Matthew T. G. Holden, Emma C. Thomson, Husam Osman, Monique Andersson, Anoop Chauhan, Mohammed O. Hassan-Ibrahim, Mara Lawniczak, Alex Alderton, Meera Chand, Chrystala Constantinidou, Meera Unnikrishnan, Alistair C. Darby, Julian A. Hiscox, Steve Paterson(University of Cambridge), Inigo Martincorena, Erik Volz, Andrew J. Page, Oliver G. Pybus, Andrew R. Bassett, Cristina V. Ariani, Michael H. Spencer Chapman, Kathy K. Li(VIR Biotechnology (United States)), Rajiv Shah, Natasha Jesudason, Yusri Taha, M. McHugh, Rebecca Dewar, Aminu S. Jahun, Claire McMurray, Sarojini Pandey, James McKenna, Andrew Nelson(National University of Singapore), Gregory R. Young, Clare M. McCann, Scott Elliott, Hannah Lowe, Ben Temperton, Sunando Roy, Anna Price(VIR Biotechnology (United States)), Sara Rey(University of Cambridge), Matthew Wyles, Stefan Rooke, Sharif Shaaban, Mariateresa de Cesare, Laura Letchford, Siona Silveira, Emanuela Pelosi, Eleri Wilson-Davies, Myra Hosmillo, Áine O’Toole, Andrew R. Hesketh, Richard Stark, Louis du Plessis, Chris Ruis(VIR Biotechnology (United States)), Helen Adams, Yann Bourgeois, Stephen L. Michell, Dimitris Grammatopoulos, Jonathan D. Edgeworth, Judith Breuer, John A. Todd, Christophe Fraser, David Buck(VIR Biotechnology (United States)), John P.T. Mo, Gemma L. Kay, Steve Palmer(University of Cambridge), Sharon J. Peacock, David Heyburn(VIR Biotechnology (United States)), Danni Weldon, Esther Robinson, Alan McNally(The Pirbright Institute), Peter Muir, Ian B. Vipond, John Boyes, Venkat Sivaprakasam, Tranprit Salluja, Samir Dervisevic, Emma Meader, Naomi R. Park, Karen Oliver, Aaron R. Jeffries, Sascha Ott, Ana da Silva Filipe, David Simpson(VIR Biotechnology (United States)), Chris Williams(VIR Biotechnology (United States)), Jane Masoli, Bridget Knight, Christopher R. Jones, Cherian Koshy, Amy Ash, Anna Casey(VIR Biotechnology (United States)), Andrew Bosworth(National University of Singapore), Liz Ratcliffe, Li Xu-McCrae(VIR Biotechnology (United States)), Hannah M. Pymont, Stephanie Hutchings, Lisa Berry(VIR Biotechnology (United States)), Katie Jones, Fenella Halstead, Thomas P. Davis, Christopher W. Holmes, Miren Iturriza-Gomara, Anita O. Lucaci, Paul Randell, Alison D. Cox, Pinglawathee Madona, Kathryn Harris, Julianne R. Brown, Tabitha Mahungu, Dianne Irish-Tavares, Tanzina Haque, Jennifer Hart, Eric Witele, Melisa Fenton, Steven Liggett(University of Cambridge), Clive Graham, Emma Swindells, Jennifer Collins, Gary Eltringham, Sharon Campbell, C. Patrick McClure, Gemma Clark, Tim J. Sloan, C. Wayne Jones, Jessica Lynch, Ben Warne, Steven Leonard(University of Cambridge), Jillian Durham, Thomas Williams, Sam Haldenby, Nathaniel Storey, Nabil-Fareed Alikhan, Nadine Holmes, Christopher Moore, Matthew Carlile, Malorie Perry, Noel Craine, Ronan A Lyons, Angela H. Beckett, Salman Goudarzi, Christopher Fearn, Kate F. Cook, Hannah Dent, Hannah Paul, Robert M. Davies(MRC University of Glasgow Centre for Virus Research), Beth Blane, Sophia T. Girgis, Mathew A. Beale, Katherine L. Bellis, Matthew J. Dorman, Eleanor Drury, Leanne Kane, Sally Kay, Samantha McGuigan, Rachel Nelson, Liam Prestwood(MRC University of Glasgow Centre for Virus Research), Shavanthi Rajatileka, Rahul Batra, Rachel Williams, Mark Kristiansen, Angie Green, Anita Justice, Adhyana I. K. Mahanama, Buddhini Samaraweera, Nazreen F. Hadjirin, Joshua Quick, Radoslaw Poplawski, Leanne M. Kermack, Nicola Reynolds, Grant Hall, Yasmin Chaudhry, Malte L. Pinckert, Iliana Georgana, Robin J. Moll, Alicia Thornton, Richard Myers, Joanne Stockton, Charlotte A. Williams, Wen C. Yew, Alexander J. Trotter, Amy Trebes, George MacIntyre-Cockett, Alec Birchley, Alexander Adams, Amy Plimmer, Bree Gatica-Wilcox, Caoimhe McKerr, Ember Hilvers, Hannah Jones, Hibo Asad, Jason Coombes, Johnathan M. Evans, Laia Fina, Lauren Gilbert, Lee Graham, Michelle Cronin, Sara Kumziene-Summerhayes(University of Cambridge), Sarah Taylor, Sophie Jones, Danielle C. Groves, Peijun Zhang, Marta Gallis, Stavroula F. Louka, Igor Starinskij, Christopher Jackson(VIR Biotechnology (United States)), Marina Gourtovaia, Gerry Tonkin‐Hill, Kevin Lewis, Jaime M. Tovar-Corona, Keith James(MRC Laboratory of Molecular Biology), Laura Baxter, Mohammad Tauqeer Alam, Richard Orton, Joseph Hughes, Vattipally B. Sreenu, Manon Ragonnet‐Cronin, Fabrícia F. Nascimento, David Jorgensen(VIR Biotechnology (United States)), Olivia Boyd, Lily Geidelberg, Alex E. Zarebski, Jayna Raghwani, Moritz U. G. Kraemer, Joel Southgate, Benjamin B. Lindsey, Timothy M. Freeman, Jon-Paul Keatley, Joshua B. Singer, Leonardo de Oliveira Martins, Corin Yeats, Khalil Abudahab, Ben Taylor, Mirko Menegazzo, John Danesh, Wendy Hogsden, Sahar Eldirdiri, Anita Kenyon(National University of Singapore), Jenifer Mason, Trevor I. Robinson, Alison Holmes, James Price(MRC Laboratory of Molecular Biology), John A. Hartley, Tanya Curran, Alison E. Mather, Giri Shankar, Rachel Jones, Robin Howe, Siân Morgan, Elizabeth Wastenge, Michael Chapman, Siddharth Mookerjee, Rachael Stanley, Wendy M. Smith, Tim Peto, David W. Eyre(VIR Biotechnology (United States)), Derrick W. Crook, Gabrielle Vernet, Christine Kitchen, Huw Gulliver, Ian Merrick(VIR Biotechnology (United States)), Martyn F. Guest, Robert J. Munn(MRC University of Glasgow Centre for Virus Research), Declan Bradley, Tim Wyatt, Charlotte Beaver, Luke Foulser, Sophie Palmer, Carol Churcher, Ellena Brooks, Kim S. Smith, Katerina Galai, Georgina M. McManus, Frances Bolt, Francesc Coll(University of Cambridge), Lizzie Meadows, Stephen W. Attwood, Alisha Davies, Elen De Lacy, Fatima Downing, Sue Edwards, Garry P. Scarlett, Sarah Jeremiah, Darren Smith, Danielle Leek, Sushmita Sridhar, Sally Forrest, Claire Cormie, Harmeet K. Gill, Joana Angélica Andrade Dias, Ellen E. Higginson, Mailis Maes, Jamie Young, Michelle Wantoch, Dorota Jamrozy, Stephanie W. Lo(The Pirbright Institute), Minal Patel, Verity Hill, Claire Bewshea, Sian Ellard, Cressida Auckland, Ian Harrison(VIR Biotechnology (United States)), Chloe Bishop, Vicki Chalker, Alex Richter, Andrew D. Beggs(National University of Singapore), Angus Best, Benita Percival, Jeremy Mirza, Oliver Megram, Megan Mayhew, Liam Crawford(MRC University of Glasgow Centre for Virus Research), Fiona Ashcroft, Emma Moles-Garcia, Nicola Cumley, Richard Hopes, Patawee Asamaphan, Marc Niebel(VIR Biotechnology (United States)), Rory Gunson, Amanda J. Bradley, Alasdair Maclean, Guy Mollett, Rachel Blacow, Paul Bird, Thomas Helmer, Karlie Fallon, Julian W. Tang, Antony Hale, Louissa Macfarlane-Smith, Katherine L. Harper, Holli Carden, Nicholas W. Machin, Kathryn Jackson, Shazaad S.Y. Ahmad, Ryan P. George, Lance Turtle, Elaine O’Toole, Joanne Watts, Cassie Breen, Angela Cowell, Adela Alcolea-Medina, Themoula Charalampous, Amita Patel, Lisa J. Levett, Judith Heaney, Aileen Rowan, Graham P. Taylor, Divya Shah, Laura Atkinson, Jack C. D. Lee, Adam Westhorpe, Riaz Jannoo, Helen L. Lowe, Angeliki Karamani, Leah Ensell, Wendy Chatterton, Monika Pusok, Ashok Dadrah, Amanda Symmonds, Graciela Sluga, Zoltán Molnár, Paul Baker, Stephen Bonner, Sarah Essex, Edward Barton, Debra Padgett, Garren Scott, Jane Greenaway, Brendan Payne, Shirelle Burton-Fanning, Sheila Waugh, Veena Raviprakash, Nicola Sheriff, Victoria Blakey, Lesley-Anne Williams, Jonathan P. Moore, Susanne Stonehouse, Louise Smith, Rose K. Davidson, Luke Bedford, Lindsay Coupland, Victoria Wright, Joseph Chappell, Theocharis Tsoleridis, Jonathan K. Ball, Manjinder Khakh, Vicki M. Fleming, Michelle M. Lister, Hannah C. Howson‐Wells, Louise Berry, Tim Boswell, Amelia Joseph, Iona Willingham, Nichola Duckworth(NHS Blood and Transplant), Sarah Walsh, Emma L. Wise, Nathan Moore, Matilde Mori, Nick Cortes, Stephen P. Kidd, Rebecca Williams, Laura Gifford, Kelly Bicknell, Sarah Wyllie, Allyson Lloyd, Robert Impey(MRC University of Glasgow Centre for Virus Research), Cassandra S. Malone, Benjamin J. Cogger, Nick Levene, Lynn Monaghan, Alexander J. Keeley, David G. Partridge, Mohammad Raza, Cariad Evans, KATE JOHNSON, Emma Betteridge, Ben W. Farr, Scott Goodwin, Michael A. Quail, Carol Scott, Lesley Shirley, Scott A. J. Thurston, Diana Rajan, Iraad F. Bronner, Louise Aigrain, Nicholas M. Redshaw(NHS Blood and Transplant), Stefanie V. Lensing, Shane McCarthy, Alex Makunin, Carlos E. Balcazar, Michael D. Gallagher, Kathleen A. Williamson, Thomas D. Stanton, Michelle L. Michelsen, Joanna Warwick-Dugdale, Robin Manley, Audrey Farbos, James W. Harrison, Christine Sambles, David J. Studholme, Angie Lackenby, Tamyo Mbisa, Steven G. Platt(University of Cambridge), Shahjahan Miah, David C. Bibby(VIR Biotechnology (United States)), Carmen de Guerrero Manso, Jonathan Hubb, Gavin Dabrera, Mary Ramsay, Daniel Bradshaw, Ulf Schaefer, Natalie Groves, Eileen Gallagher, David Lee(VIR Biotechnology (United States)), David A. Williams(VIR Biotechnology (United States)), Nicholas Ellaby(NHS Blood and Transplant), Hassan Hartman, Nikos Manesis, Vineet Patel, Juan Ledesma, Katherine A. Twohig, Elias Allara, Clare Pearson, Jeffrey K. J. Cheng, Hannah E. Bridgewater, Lucy R. Frost, Grace Taylor-Joyce, Paul E. Brown, L. Tong, Alice Broos, Daniel Mair, Jenna Nichols, Stephen Carmichael, Katherine Smollett, Kyriaki Nomikou, Elihú Aranday-Cortés, Natasha Johnson, Seema Nickbakhsh, Edith E. Vamos, Margaret Hughes, Lucille Rainbow, Richard Eccles, Charlotte Nelson, Mark Whitehead, Richard D. Gregory, Matthew Gemmell, Claudia Wierzbicki, Hermione J. Webster, Chloe L. Fisher, Adrian W. Signell, Gilberto Betancor, Harry Wilson, Gaia Nebbia, Flavia Flaviani, Alberto C. Cerda, Tammy V. Merrill, Rebekah E. Wilson, Marius Cotic, Nadua Bayzid, Thomas Thompson, Erwan Acheson, Steven Rushton(University of Cambridge), Sarah H. O’Brien, David Baker, Steven Rudder(University of Cambridge), Alp Aydin, Fei Sang, Johnny Debebe, Sarah François, Tetyana I. Vasylyeva, Marina Escalera Zamudio, Bernardo Gutiérrez, Angela Marchbank, Joshua Maksimovic, Karla Spellman, Kathryn McCluggage, Mari Morgan, Robert Beer(MRC University of Glasgow Centre for Virus Research), Safiah Afifi, Trudy Workman, William Fuller(MRC University of Glasgow Centre for Virus Research), Catherine Bresner, Adrienn Angyal, Luke R. Green, Paul J. Parsons, Rachel Tucker, Rebecca Brown, Max Whiteley, James Bonfield(MRC Laboratory of Molecular Biology), Christoph Puethe, Andrew Whitwham(National University of Singapore), Jennifier Liddle, Will Rowe(MRC University of Glasgow Centre for Virus Research), Igor Siveroni, Thanh Le-Viet, Amy Gaskin, Rob Johnson(MRC University of Glasgow Centre for Virus Research), Irina Abnizova, Mozam Ali(VIR Biotechnology (United States)), Laura K. Allen, Ralph Anderson, Cristina V. Ariani, Siobhan Austin-Guest, Sendu Bala, Jeffrey C. Barrett, Andrew R. Bassett(National University of Singapore), Kristina Battleday, James R. Beal(MRC Laboratory of Molecular Biology), Mathew A. Beale, Sam Bellany, Tristram Bellerby, Katie Bellis, Duncan Berger(University of Cambridge), Matthew Berriman, Paul Bevan, Simon Binley, Jason Bishop, Kirsty Blackburn, Nick Boughton, Sam Bowker, Timothy Brendler-Spaeth, Iraad F. Bronner, Tanya Brooklyn, Sarah K. Buddenborg, Robert K. Bush(MRC University of Glasgow Centre for Virus Research), Catarina Caetano, Alex Cagan, Nicola Carter, Joanna Cartwright, Tiago Monteiro, Liz Chapman, Tracey-Jane Chillingworth, Peter Clapham, Richard Clark, Adrian Clarke, Catriona Clarke, Daryl Cole, Elizabeth Cook, Maria Coppola, Linda Cornell, Clare Cornwell, Craig Corton, Abby Crackett, Alison Cranage, Harriet Craven, Sarah Craw, Mark Crawford, Tim Cutts, Monika Dabrowska, Matt Davies, Joseph Dawson, Callum Day, Aiden Densem, Thomas Dibling, Cat Dockree, D. C. Dodd(VIR Biotechnology (United States)), Sunil Kumar Dogga, Matthew J. Dorman, Gordon Dougan, Martin Dougherty, Alexander Dove, Lucy Drummond, Monika Dudek, Laura Durrant, Elizabeth Easthope, Sabine Eckert, Peter Ellis, Ben W. Farr, Michael Fenton, Marcella Ferrero, Neil Flack, Howerd Fordham, Grace Forsythe, Matt Francis, Audrey Fraser, Adam Freeman, Anastasia Galvin, Maria Garcia-Casado, Alex Gedny, Sophia T. Girgis, James Glover(MRC Laboratory of Molecular Biology), Oliver Gould, Andy Gray, Emma Gray, Chris Griffiths, Yong Gu(University of Cambridge), Florence Guerin, William L. Hamilton(MRC University of Glasgow Centre for Virus Research), H. Douglas Hanks, Ewan M. Harrison, Alexandria Harrott, Edward Harry, Julia Harvison(National University of Singapore), Paul T. Heath, Anastasia Hernández-Koutoucheva, Rhiannon Hobbs, Dave Holland, Sarah Holmes, Gary Hornett, Nicholas Hough(NHS Blood and Transplant), Liz Huckle, Lena Hughes-Hallet, Adam Hunter, Stephen Inglis, Sameena Iqbal, Adam Jackson, David K. Jackson(VIR Biotechnology (United States)), Carlos Jimenez Verdejo, Matthew Jones, Kalyan Kallepally, Keely Kay, Jon Keatley, Alan Keith(The Pirbright Institute), Alison J. King, Lucy Kitchin, Matt Kleanthous, Martina Klimekova, Petra Korlević(University of Cambridge), Ksenia Krasheninnkova, Greg Lane, Cordelia Langford, Adam Laverack, Katharine Law, Stefanie V. Lensing, Amanah Lewis-Wade, Jennifer Liddle, Quan Lin(University of Cambridge), Sarah Lindsay, Sally Linsdell, Rhona Long, Jamie Lovell, Jon Lovell, James Mack(MRC Laboratory of Molecular Biology), Mark Maddison, Aleksei Makunin, Irfan Mamun, Jenny Mansfield, Neil Marriott, Matthew Martin, Matthew Mayho, Jo McClintock, Sandra McHugh, Liz MapcMinn, Carl Meadows, Emily Mobley, Robin J. Moll, Maria Morra, Leanne Morrow, Kathryn Murie, Sian Nash, Claire Nathwani, Plamena Naydenova, Alexandra Neaverson, Ed Nerou(The Pirbright Institute), Jon Nicholson, Tabea Nimz, Guillaume Noell, Sarah O’Meara, Valeriu Ohan, Charles Olney, Doug Ormond, Ágnes Oszlánczi, Yoke Fei Pang, Barbora Pardubska, Naomi Park, Aaron Parmar, Gaurang Patel, Maggie Payne, Sharon J. Peacock, Arabella Petersen, Deborah Plowman, Tom Preston, Michael A. Quail, Richard Rance, Suzannah Rawlings(University of Cambridge), Nicholas Redshaw(NHS Blood and Transplant), Joe Reynolds, Mark Reynolds, Simon Rice, Matt Richardson, Connor Roberts(MRC University of Glasgow Centre for Virus Research), Katrina Robinson, Melanie Robinson, David M. Robinson(VIR Biotechnology (United States)), Hazel Rogers, Eduardo Martin Rojo, Daljit Roopra, Mark E. Rose, Luke Rudd, Ramin Sadri, Nicholas Salmon(NHS Blood and Transplant), David Saul(VIR Biotechnology (United States)), Frank Schwach, Phil Seekings, Alison Simms, Matt D. Sinnott, Shanthi Sivadasan, Bart Siwek, Dale Sizer, Kenneth Skeldon, Jason Skelton, Joanna Slater-Tunstill, Lisa Sloper(VIR Biotechnology (United States)), Nathalie Smerdon, Chris Smith(VIR Biotechnology (United States)), Christen Smith, J. L. Smith(MRC Laboratory of Molecular Biology), Katie Smith, Michelle Smith, Sean B. Smith, Tina Smith, Leighton Sneade, C. Soria, Catarina Sousa, Emily Souster, Andrew Sparkes(National University of Singapore), Michael Spencer-Chapman, Janet Squares, Robert Stanley(MRC University of Glasgow Centre for Virus Research), Claire Steed, Tim Stickland, Ian Still(VIR Biotechnology (United States)), Mike Stratton, Michelle Strickland, Allen Swann, Agnieszka Świątkowska, Neil Sycamore, Emma Swift, Edward Symons, Suzanne Szluha, Emma Taluy, Nunu Tao, Katy Taylor, Sam Taylor, Stacey Thompson, Mark A. Thompson, M. Thomson, Nicholas M. Thomson(NHS Blood and Transplant), Scott Thurston, Dee Toombs, Benjamin Topping, Jaime M. Tovar-Corona, Daniel Ungureanu, James Uphill(MRC Laboratory of Molecular Biology), Jana Urbanová, Philip Jansen Van, Valerie E. Vancollie, Paul Voak, Danielle Walker, Matthew Walker, Matt Waller, Gary H. Ward, Charlie Weatherhogg, Niki Webb, Alan Wells(The Pirbright Institute), Eloise Wells, Luke Westwood, Theo Whipp, Thomas Whiteley, Georgia Whitton, Sara Widaa(University of Cambridge), Mia Kim Williams, Mark Wilson, Sean Wright, Lidia M. Duncan(University of Cambridge), Alessandro M. Carabelli(University of Cambridge), Julia C. Kenyon(National University of Singapore), Andrew Lever(National University of Singapore), Anna De Marco(Vir Biotechnology (Switzerland)), Christian Saliba(Vir Biotechnology (Switzerland)), Katja Culap(Vir Biotechnology (Switzerland)), Elisabetta Cameroni(Vir Biotechnology (Switzerland)), Nicholas J. Matheson(NHS Blood and Transplant), Luca Piccoli(Vir Biotechnology (Switzerland)), Davide Corti(Vir Biotechnology (Switzerland)), Leo C. James(MRC Laboratory of Molecular Biology), David L. Robertson(MRC University of Glasgow Centre for Virus Research), Dalan Bailey(The Pirbright Institute), Ravindra K. Gupta(University of Cambridge)
Cited by 450Open Access
Abstract
We report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike ΔH69/V70 in multiple independent lineages, often occurring after acquisition of receptor binding motif replacements such as N439K and Y453F, known to increase binding affinity to the ACE2 receptor and confer antibody escape. In vitro, we show that, although ΔH69/V70 itself is not an antibody evasion mechanism, it increases infectivity associated with enhanced incorporation of cleaved spike into virions. ΔH69/V70 is able to partially rescue infectivity of spike proteins that have acquired N439K and Y453F escape mutations by increased spike incorporation. In addition, replacement of the H69 and V70 residues in the Alpha variant B.1.1.7 spike (where ΔH69/V70 occurs naturally) impairs spike incorporation and entry efficiency of the B.1.1.7 spike pseudotyped virus. Alpha variant B.1.1.7 spike mediates faster kinetics of cell-cell fusion than wild-type Wuhan-1 D614G, dependent on ΔH69/V70. Therefore, as ΔH69/V70 compensates for immune escape mutations that impair infectivity, continued surveillance for deletions with functional effects is warranted.
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