학술논문
Recurrent emergence of SARS-CoV-2 spike deletion H69/V70 and its role in the Alpha variant B.1.1.7
Document Type
article
Author
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 Mlcochova; Lidia M. Duncan; Alessandro M. Carabelli; Julia C. Kenyon; Andrew M. 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; 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 R. Awan; Giselda Bucca; M. Estee Torok; Kordo Saeed; Jacqui A. Prieto; David K. Jackson; William L. Hamilton; Luke B. Snell; Catherine Moore; Ewan M. Harrison; Sonia Goncalves; Derek J. Fairley; Matthew W. Loose; Joanne Watkins; Rich Livett; Samuel Moses; Roberto Amato; Sam Nicholls; Matthew Bull; Darren L. 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 E. 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 J. 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 M. Volz; Andrew J. Page; Oliver G. Pybus; Andrew R. Bassett; Cristina V. Ariani; Michael H. Spencer Chapman; Kathy K. Li; Rajiv N. Shah; Natasha G. Jesudason; Yusri Taha; Martin P. McHugh; Rebecca Dewar; Aminu S. Jahun; Claire McMurray; Sarojini Pandey; James P. 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 Gramatopoulos; Jonathan Edgeworth; Judith Breuer; John A. Todd; Christophe Fraser; David Buck; Michaela John; 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 J. Meader; Naomi R. Park; Karen Oliver; Aaron R. Jeffries; Sascha Ott; Ana da Silva Filipe; David A. Simpson; Chris Williams; Jane A.H. Masoli; Bridget A. 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 Davis; Christopher Holmes; Miren Iturriza-Gomara; Anita O. Lucaci; Paul Anthony Randell; Alison Cox; Pinglawathee Madona; Kathryn Ann Harris; Julianne Rose Brown; Tabitha W. Mahungu; Dianne Irish-Tavares; Tanzina Haque; Jennifer Hart; Eric Witele; Melisa Louise Fenton; Steven Liggett; Clive Graham; Emma Swindells; Jennifer Collins; Gary Eltringham; Sharon Campbell; Patrick C. McClure; Gemma Clark; Tim J. Sloan; Carl Jones; Jessica Lynch; Ben Warne; Steven Leonard; Jillian Durham; Thomas Williams; Sam T. 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 Cook; Hannah Dent; Hannah Paul; Robert Davies; 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; Shavanthi Rajatileka; Rahul Batra; Rachel J. 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; Chris Jackson; Marina Gourtovaia; Gerry Tonkin-Hill; Kevin Lewis; Jaime M. Tovar-Corona; Keith James; Laura Baxter; Mohammad T. Alam; Richard J. Orton; Joseph Hughes; Sreenu Vattipally; Manon Ragonnet-Cronin; Fabricia F. Nascimento; David Jorgensen; 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 A. Yeats; Khalil Abudahab; Ben E.W. Taylor; Mirko Menegazzo; John Danesh; Wendy Hogsden; Sahar Eldirdiri; Anita Kenyon; Jenifer Mason; Trevor I. Robinson; Alison Holmes; James Price; John A. Hartley; Tanya Curran; Alison E. Mather; Giri Shankar; Rachel Jones; Robin Howe; Sian Morgan; Elizabeth Wastenge; Michael R. Chapman; Siddharth Mookerjee; Rachael Stanley; Wendy Smith; Timothy Peto; David Eyre; Derrick Crook; Gabrielle Vernet; Christine Kitchen; Huw Gulliver; Ian Merrick; Martyn Guest; Robert Munn; Declan T. Bradley; Tim Wyatt; Charlotte Beaver; Luke Foulser; Sophie Palmer; Carol M. Churcher; Ellena Brooks; Kim S. Smith; Katerina Galai; Georgina M. McManus; Frances Bolt; Francesc Coll; Lizzie Meadows; Stephen W. Attwood; Alisha Davies; Elen De Lacy; Fatima Downing; Sue Edwards; Garry P. Scarlett; Sarah Jeremiah; Nikki Smith; Danielle Leek; Sushmita Sridhar; Sally Forrest; Claire Cormie; Harmeet K. Gill; Joana Dias; Ellen E. Higginson; Mailis Maes; Jamie Young; Michelle Wantoch; Dorota Jamrozy; Stephanie Lo; Minal Patel; Verity Hill; Claire M. Bewshea; Sian Ellard; Cressida Auckland; Ian Harrison; Chloe Bishop; Vicki Chalker; Alex Richter; Andrew Beggs; Angus Best; Benita Percival; Jeremy Mirza; Oliver Megram; Megan Mayhew; Liam Crawford; Fiona Ashcroft; Emma Moles-Garcia; Nicola Cumley; Richard Hopes; Patawee Asamaphan; Marc O. Niebel; Rory N. Gunson; Amanda Bradley; Alasdair Maclean; Guy Mollett; Rachel Blacow; Paul Bird; Thomas Helmer; Karlie Fallon; Julian Tang; Antony D. Hale; Louissa R. Macfarlane-Smith; Katherine L. Harper; Holli Carden; Nicholas W. Machin; Kathryn A. 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 P. Westhorpe; Riaz Jannoo; Helen L. Lowe; Angeliki Karamani; Leah Ensell; Wendy Chatterton; Monika Pusok; Ashok Dadrah; Amanda Symmonds; Graciela Sluga; Zoltan Molnar; Paul Baker; Stephen Bonner; Sarah Essex; Edward Barton; Debra Padgett; Garren Scott; Jane Greenaway; Brendan A.I. Payne; Shirelle Burton-Fanning; Sheila Waugh; Veena Raviprakash; Nicola Sheriff; Victoria Blakey; Lesley-Anne Williams; Jonathan Moore; Susanne Stonehouse; Louise Smith; Rose K. Davidson; Luke Bedford; Lindsay Coupland; Victoria Wright; Joseph G. Chappell; Theocharis Tsoleridis; Jonathan Ball; Manjinder Khakh; Vicki M. Fleming; Michelle M. Lister; Hannah C. Howson-Wells; Louise Berry; Tim Boswell; Amelia Joseph; Iona Willingham; Nichola Duckworth; Sarah Walsh; Emma Wise; Nathan Moore; Matilde Mori; Nick Cortes; Stephen Kidd; Rebecca Williams; Laura Gifford; Kelly Bicknell; Sarah Wyllie; Allyson Lloyd; Robert Impey; 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; 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 M. Sambles; David J. Studholme; Angie Lackenby; Tamyo Mbisa; Steven Platt; Shahjahan Miah; David Bibby; Carmen Manso; Jonathan Hubb; Gavin Dabrera; Mary Ramsay; Daniel Bradshaw; Ulf Schaefer; Natalie Groves; Eileen Gallagher; David Lee; David Williams; Nicholas Ellaby; 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; Lily Tong; Alice Broos; Daniel Mair; Jenna Nichols; Stephen N. Carmichael; Katherine L. Smollett; Kyriaki Nomikou; Elihu Aranday-Cortes; Natasha Johnson; Seema Nickbakhsh; Edith E. Vamos; Margaret Hughes; Lucille Rainbow; Richard Eccles; Charlotte Nelson; Mark Whitehead; Richard Gregory; Matthew Gemmell; Claudia Wierzbicki; Hermione J. Webster; Chloe L. Fisher; Adrian W. Signell; Gilberto Betancor; Harry D. Wilson; Gaia Nebbia; Flavia Flaviani; Alberto C. Cerda; Tammy V. Merrill; Rebekah E. Wilson; Marius Cotic; Nadua Bayzid; Thomas Thompson; Erwan Acheson; Steven Rushton; Sarah O’Brien; David J. Baker; Steven Rudder; Alp Aydin; Fei Sang; Johnny Debebe; Sarah Francois; Tetyana I. Vasylyeva; Marina Escalera Zamudio; Bernardo Gutierrez; Angela Marchbank; Joshua Maksimovic; Karla Spellman; Kathryn McCluggage; Mari Morgan; Robert Beer; Safiah Afifi; Trudy Workman; William Fuller; Catherine Bresner; Adrienn Angyal; Luke R. Green; Paul J. Parsons; Rachel M. Tucker; Rebecca Brown; Max Whiteley; James Bonfield; Christoph Puethe; Andrew Whitwham; Jennifier Liddle; Will Rowe; Igor Siveroni; Thanh Le-Viet; Amy Gaskin; Rob Johnson; Irina Abnizova; Mozam Ali; Laura Allen; Ralph Anderson; Cristina Ariani; Siobhan Austin-Guest; Sendu Bala; Jeffrey Barrett; Andrew Bassett; Kristina Battleday; James Beal; Mathew Beale; Sam Bellany; Tristram Bellerby; Katie Bellis; Duncan Berger; Matt Berriman; Paul Bevan; Simon Binley; Jason Bishop; Kirsty Blackburn; Nick Boughton; Sam Bowker; Timothy Brendler-Spaeth; Iraad Bronner; Tanya Brooklyn; Sarah Kay Buddenborg; Robert Bush; Catarina Caetano; Alex Cagan; Nicola Carter; Joanna Cartwright; Tiago Carvalho 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; David Dodd; Sunil Dogga; Matthew Dorman; Gordon Dougan; Martin Dougherty; Alexander Dove; Lucy Drummond; Monika Dudek; Laura Durrant; Elizabeth Easthope; Sabine Eckert; Pete Ellis; Ben 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 Girgis; James Glover; Oliver Gould; Andy Gray; Emma Gray; Coline Griffiths; Yong Gu; Florence Guerin; Will Hamilton; Hannah Hanks; Ewan Harrison; Alexandria Harrott; Edward Harry; Julia Harvison; Paul Heath; Anastasia Hernandez-Koutoucheva; Rhiannon Hobbs; Dave Holland; Sarah Holmes; Gary Hornett; Nicholas Hough; Liz Huckle; Lena Hughes-Hallet; Adam Hunter; Stephen Inglis; Sameena Iqbal; Adam Jackson; David Jackson; Carlos Jimenez Verdejo; Matthew Jones; Kalyan Kallepally; Keely Kay; Jon Keatley; Alan Keith; Alison King; Lucy Kitchin; Matt Kleanthous; Martina Klimekova; Petra Korlevic; Ksenia Krasheninnkova; Greg Lane; Cordelia Langford; Adam Laverack; Katharine Law; Stefanie Lensing; Amanah Lewis-Wade; Jennifer Liddle; Quan Lin; Sarah Lindsay; Sally Linsdell; Rhona Long; Jamie Lovell; Jon Lovell; James Mack; Mark Maddison; Aleksei Makunin; Irfan Mamun; Jenny Mansfield; Neil Marriott; Matt Martin; Matthew Mayho; Jo McClintock; Sandra McHugh; Liz MapcMinn; Carl Meadows; Emily Mobley; Robin Moll; Maria Morra; Leanne Morrow; Kathryn Murie; Sian Nash; Claire Nathwani; Plamena Naydenova; Alexandra Neaverson; Ed Nerou; Jon Nicholson; Tabea Nimz; Guillaume G. Noell; Sarah O’Meara; Valeriu Ohan; Charles Olney; Doug Ormond; Agnes Oszlanczi; Yoke Fei Pang; Barbora Pardubska; Naomi Park; Aaron Parmar; Gaurang Patel; Maggie Payne; Sharon Peacock; Arabella Petersen; Deborah Plowman; Tom Preston; Michael Quail; Richard Rance; Suzannah Rawlings; Nicholas Redshaw; Joe Reynolds; Mark Reynolds; Simon Rice; Matt Richardson; Connor Roberts; Katrina Robinson; Melanie Robinson; David Robinson; Hazel Rogers; Eduardo Martin Rojo; Daljit Roopra; Mark Rose; Luke Rudd; Ramin Sadri; Nicholas Salmon; David Saul; Frank Schwach; Phil Seekings; Alison Simms; Matt Sinnott; Shanthi Sivadasan; Bart Siwek; Dale Sizer; Kenneth Skeldon; Jason Skelton; Joanna Slater-Tunstill; Lisa Sloper; Nathalie Smerdon; Chris Smith; Christen Smith; James Smith; Katie Smith; Michelle Smith; Sean Smith; Tina Smith; Leighton Sneade; Carmen Diaz Soria; Catarina Sousa; Emily Souster; Andrew Sparkes; Michael Spencer-Chapman; Janet Squares; Robert Stanley; Claire Steed; Tim Stickland; Ian Still; Mike Stratton; Michelle Strickland; Allen Swann; Agnieszka Swiatkowska; Neil Sycamore; Emma Swift; Edward Symons; Suzanne Szluha; Emma Taluy; Nunu Tao; Katy Taylor; Sam Taylor; Stacey Thompson; Mark Thompson; Mark Thomson; Nicholas Thomson; Scott Thurston; Dee Toombs; Benjamin Topping; Jaime Tovar-Corona; Daniel Ungureanu; James Uphill; Jana Urbanova; Philip Jansen Van; Valerie Vancollie; Paul Voak; Danielle Walker; Matthew Walker; Matt Waller; Gary Ward; Charlie Weatherhogg; Niki Webb; Alan Wells; Eloise Wells; Luke Westwood; Theo Whipp; Thomas Whiteley; Georgia Whitton; Sara Widaa; Mia Williams; Mark Wilson; Sean Wright
Source
Cell Reports, Vol 35, Iss 13, Pp 109292- (2021)
Subject
Language
English
ISSN
2211-1247
Abstract
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.