Open AccessRecurrent emergence of SARS-CoV-2 spike deletion H69/V70 and its role in the Alpha variant B.1.1.7
Author(s) -
Bo Meng,
Steven A. Kemp,
Guido Papa,
Rawlings Datir,
Isabella A. T. M. Ferreira,
Sara Marelli,
William T. Harvey,
Spyros Lytras,
Ahmed Mohamed,
Giulia Gallo,
Nazia Thakur,
Dami A. Collier,
Petra Mlčochová,
Samuel C. Robson,
Nicholas J. Loman,
Thomas R. Connor,
Tanya Golubchik,
Rocio T. Martinez Nunez,
Catherine Ludden,
Sally Corden,
Ian Johnston,
David Bonsall,
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,
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,
Inigo Martincorena,
Erik Volz,
Andrew J. Page,
Oliver G. Pybus,
Andrew R. Bassett,
Cristina V. Ariani,
Michael H. Spencer Chapman,
Kathy K. Li,
Rajiv Shah,
Natasha Jesudason,
Yusri Taha,
M. McHugh,
Rebecca Dewar,
Aminu S. Jahun,
Claire McMurray,
Sarojini Pandey,
James McKenna,
Andrew Nelson,
Gregory R. Young,
Clare M. McCann,
Scott Elliott,
Hannah Lowe,
Ben Temperton,
Sunando Roy,
Anna Price,
Sara Rey,
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,
Helen Adams,
Yann Bourgeois,
Stephen L. Michell,
Dimitris K. Grammatopoulos,
Jonathan D. Edgeworth,
Judith Breuer,
John A. Todd,
Christophe Fraser,
David Buck,
John P.T. Mo,
Gemma L. Kay,
Steve Palmer,
Sharon J. Peacock,
David Heyburn,
Danni Weldon,
Esther Robinson,
Alan McNally,
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,
Chris Williams,
Jane Masoli,
Bridget Knight,
Christopher R. Jones,
Cherian Koshy,
Amy Ash,
Anna Casey,
Andrew Bosworth,
Liz Ratcliffe,
Li Xu-McCrae,
Hannah M. Pymont,
Stephanie Hutchings,
Lisa Berry,
Katie Jones,
Fenella Halstead,
Thomas P. Davis,
Christopher W. Holmes,
Miren Iturriza-Gomara,
Anita O. Lucaci,
Paul Randell,
Alison Cox,
Pinglawathee Madona,
Kathryn Harris,
Julianne R. Brown,
Tabitha Mahungu,
Dianne Irish-Tavares,
Tanzina Haque,
Jennifer Hart,
Eric Witele,
Melisa Fenton,
Steven Liggett,
Clive Graham,
Emma Swindells,
Jennifer Collins,
Gary Eltringham,
Stephen Campbell,
C. Patrick McClure,
Gemma Clark,
Tim J. Sloan,
C. Wayne Jones,
Jessica Lynch,
Ben Warne,
Steven N. Leonard,
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,
Beth Blane,
Sophia T. Girgis,
Mathew A. Beale,
Katherine L. Bellis,
Matthew J. Dorman,
Eleanor Drury,
Leanne Kane,
Sally Kay,
Samantha McGuigan,
Liam Prestwood,
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,
Sarah Taylor,
Sophie Jones,
Danielle C. Groves,
Peijun Zhang,
Marta Gallis,
Stavroula F. Louka,
Igor Starinskij,
Christopher Jackson,
Marina Gourtovaia,
Gerry TonkinHill,
Kevin Lewis,
Jaime M. Tovar-Corona,
Keith James,
Laura Baxter,
Mohammad Tauqeer Alam,
Richard Orton,
Joseph Hughes,
Vattipally B. Sreenu,
Ma RagonnetCronin,
Fabrícia F. Nascimento,
David Jorgensen,
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Jayna Raghwani,
Moritz U. G. Kraemer,
Joel Southgate,
Benjamin B. Lindsey,
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Khalil Abudahab,
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Jenifer Mason,
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Alison Holmes,
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Alison E. Mather,
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Robin Howe,
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Jason Skelton,
Joanna Slater-Tunstill,
Lisa Sloper,
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Chris Smith,
Christen Smith,
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Katie Smith,
Michelle Smith,
Sean B. Smith,
Tina Smith,
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Andrew Sparkes,
Michael Spencer-Chapman,
Janet Squares,
Robert Stanley,
Claire Steed,
Tim Stickland,
Ian Still,
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,
Scott Thurston,
Dee Toombs,
Benjamin Topping,
Daniel Ungureanu,
James Uphill,
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,
Eloise Wells,
Luke Westwood,
Theo Whipp,
Thomas Whiteley,
Georgia Whitton,
Sara Widaa,
Mia Kim Williams,
Mark Wilson,
Sean Wright,
Lidia M. Duncan,
Alessandro M. Carabelli,
Julia C. Kenyon,
Andrew Lever,
Anna De Marco,
Christian Saliba,
Katja Culap,
Elisabetta Cameroni,
Nicholas J. Matheson,
Luca Piccoli,
Davide Corti,
Leo C. James,
David L. Robertson,
Dalan Bailey,
Ravindra K. Gupta
Publication year - 2021
Publication title -
cell reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.264
H-Index - 154
eISSN - 2639-1856
pISSN - 2211-1247
DOI - 10.1016/j.celrep.2021.109292
Subject(s) - infectivity , spike (software development) , spike protein , receptor , biology , covid-19 , antibody , virology , chemistry , virus , immunology , genetics , medicine , management , disease , infectious disease (medical specialty) , economics
Summary 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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