Recurrent emergence of SARS-CoV-2 spike deletion H69/V70 and its role in the Alpha variant B.1.1.7
Meng B, Kemp SA, Papa G, Datir R, Ferreira IATM, Marelli S, Harvey WT, Lytras S, Mohamed A, Gallo G, Thakur N, Collier DA, Mlcochova P, Robson SC, Loman NJ, Connor TR, Golubchik T, Martinez Nunez RT, Ludden C, Corden S, Johnston I, Bonsall D, Smith CP, Awan AR, Bucca G, Torok ME, Saeed K, Prieto JA, Jackson DK, Hamilton WL, Snell LB, Moore C, Harrison EM, Goncalves S, Fairley DJ, Loose MW, Watkins J, Livett R, Moses S, Amato R, Nicholls S, Bull M, Smith DL, Barrett J, Aanensen DM, Curran MD, Parmar S, Aggarwal D, Shepherd JG, Parker MD, Glaysher S, Bashton M, Underwood AP, Pacchiarini N, Loveson KF, Templeton KE, Langford CF, Sillitoe J, de Silva TI, Wang D, Kwiatkowski D, Rambaut A, O'Grady J, Cottrell S, Holden MTG, Thomson EC, Osman H, Andersson M, Chauhan AJ, Hassan-Ibrahim MO, Lawniczak M, Alderton A, Chand M, Constantinidou C, Unnikrishnan M, Darby AC, Hiscox JA, Paterson S, Martincorena I, Volz EM, Page AJ, Pybus OG, Bassett AR, Ariani CV, Chapman MHS, Li KK, Shah RN, Jesudason NG, Taha Y, McHugh MP, Dewar R, Jahun AS, McMurray C, Pandey S, McKenna JP, Nelson A, Young GR, McCann CM, 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, Hosmillo M, O'Toole Á, Hesketh AR, Stark R, du Plessis L, Ruis C, Adams H, Bourgeois Y, Michell SL, Gramatopoulos D, Edgeworth J, Breuer J, Todd JA, Fraser C, Buck D, John M, Kay GL, Palmer S, Peacock SJ, Heyburn D, Weldon D, Robinson E, McNally A, Muir P, Vipond IB, Boyes J, Sivaprakasam V, Salluja T, Dervisevic S, Meader EJ, Park NR, Oliver K, Jeffries AR, Ott S, da Silva Filipe A, Simpson DA, Williams C, Masoli JAH, Knight BA, Jones CR, Koshy C, Ash A, Casey A, Bosworth A, Ratcliffe L, Xu-McCrae L, Pymont HM, Hutchings S, Berry L, Jones K, Halstead F, Davis T, Holmes C, Iturriza-Gomara M, Lucaci AO, Randell PA, Cox A, Madona P, Harris KA, Brown JR, Mahungu TW, Irish-Tavares D, Haque T, Hart J, Witele E, Fenton ML, Liggett S, Graham C, Swindells E, Collins J, Eltringham G, Campbell S, McClure PC, Clark G, Sloan TJ, Jones C, Lynch J, Warne B, Leonard S, Durham J, Williams T, Haldenby ST, Storey N, Alikhan N-F, Holmes N, Moore C, Carlile M, Perry M, Craine N, Lyons RA, Beckett AH, Goudarzi S, Fearn C, Cook K, Dent H, Paul H, Davies R, Blane B, Girgis ST, Beale MA, Bellis KL, Dorman MJ, Drury E, Kane L, Kay S, McGuigan S, Nelson R, Prestwood L, Rajatileka S, Batra R, Williams RJ, Kristiansen M, Green A, Justice A, Mahanama AIK, Samaraweera B, Hadjirin NF, Quick J, Poplawski R, Kermack LM, Reynolds N, Hall G, Chaudhry Y, Pinckert ML, Georgana I, Moll RJ, Thornton A, Myers R, Stockton J, Williams CA, Yew WC, Trotter AJ, 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 JM, Fina L, Gilbert L, Graham L, Cronin M, Kumziene-Summerhayes S, Taylor S, Jones S, Groves DC, Zhang P, Gallis M, Louka SF, Starinskij I, Jackson C, Gourtovaia M, Tonkin-Hill G, Lewis K, Tovar-Corona JM, James K, Baxter L, Alam MT, Orton RJ, Hughes J, Vattipally S, Ragonnet-Cronin M, Nascimento FF, Jorgensen D, Boyd O, Geidelberg L, Zarebski AE, Raghwani J, Kraemer MUG, Southgate J, Lindsey BB, Freeman TM, Keatley J-P, Singer JB, de Oliveira Martins L, Yeats CA, Abudahab K, Taylor BEW, Menegazzo M, Danesh J, Hogsden W, Eldirdiri S, Kenyon A, Mason J, Robinson TI, Holmes A, Price J, Hartley JA, Curran T, Mather AE, Shankar G, Jones R, Howe R, Morgan S, Wastenge E, Chapman MR, 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 DT, Wyatt T, Beaver C, Foulser L, Palmer S, Churcher CM, Brooks E, Smith KS, Galai K, McManus GM, Bolt F, Coll F, Meadows L, Attwood SW, Davies A, De Lacy E, Downing F, Edwards S, Scarlett GP, Jeremiah S, Smith N, Leek D, Sridhar S, Forrest S, Cormie C, Gill HK, Dias J, Higginson EE, Maes M, Young J, Wantoch M, Jamrozy D, Lo S, Patel M, Hill V, Bewshea CM, 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 MO, Gunson RN, Bradley A, Maclean A, Mollett G, Blacow R, Bird P, Helmer T, Fallon K, Tang J, Hale AD, Macfarlane-Smith LR, Harper KL, Carden H, Machin NW, Jackson KA, Ahmad SSY, George RP, Turtle L, O'Toole E, Watts J, Breen C, Cowell A, Alcolea-Medina A, Charalampous T, Patel A, Levett LJ, Heaney J, Rowan A, Taylor GP, Shah D, Atkinson L, Lee JCD, Westhorpe AP, Jannoo R, Lowe HL, 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 BAI, Burton-Fanning S, Waugh S, Raviprakash V, Sheriff N, Blakey V, Williams L-A, Moore J, Stonehouse S, Smith L, Davidson RK, Bedford L, Coupland L, Wright V, Chappell JG, Tsoleridis T, Ball J, Khakh M, Fleming VM, Lister MM, Howson-Wells HC, Berry L, 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 CS, Cogger BJ, Levene N, Monaghan L, Keeley AJ, Partridge DG, Raza M, Evans C, Johnson K, Betteridge E, Farr BW, Goodwin S, Quail MA, Scott C, Shirley L, Thurston SAJ, Rajan D, Bronner IF, Aigrain L, Redshaw NM, Lensing SV, McCarthy S, Makunin A, Balcazar CE, Gallagher MD, Williamson KA, Stanton TD, Michelsen ML, Warwick-Dugdale J, Manley R, Farbos A, Harrison JW, Sambles CM, Studholme DJ, 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 KA, Allara E, Pearson C, Cheng JKJ, Bridgewater HE, Frost LR, Taylor-Joyce G, Brown PE, Tong L, Broos A, Mair D, Nichols J, Carmichael SN, Smollett KL, Nomikou K, Aranday-Cortes E, Johnson N, Nickbakhsh S, Vamos EE, Hughes M, Rainbow L, Eccles R, Nelson C, Whitehead M, Gregory R, Gemmell M, Wierzbicki C, Webster HJ, Fisher CL, Signell AW, Betancor G, Wilson HD, Nebbia G, Flaviani F, Cerda AC, Merrill TV, Wilson RE, Cotic M, Bayzid N, Thompson T, Acheson E, Rushton S, O'Brien S, Baker DJ, Rudder S, Aydin A, Sang F, Debebe J, Francois S, Vasylyeva TI, Zamudio ME, 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 LR, Parsons PJ, Tucker RM, Brown R, Whiteley M, Bonfield J, Puethe C, Whitwham A, Liddle J, Rowe W, Siveroni I, Le-Viet T, Gaskin A, Johnson R, Abnizova I, Ali M, Allen L, Anderson R, Ariani C, Austin-Guest S, Bala S, Barrett J, Bassett A, Battleday K, Beal J, Beale M, Bellany S, Bellerby T, Bellis K, Berger D, Berriman M, Bevan P, Binley S, Bishop J, Blackburn K, Boughton N, Bowker S, Brendler-Spaeth T, Bronner I, Brooklyn T, Buddenborg SK, Bush R, Caetano C, Cagan A, Carter N, Cartwright J, Monteiro TC, 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, Dorman M, Dougan G, 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, 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 CJ, 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, Lovell J, Mack J, Maddison M, Makunin A, Mamun I, Mansfield J, Marriott N, Martin M, Mayho M, McClintock J, McHugh S, MapcMinn 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 GG, O'Meara S, Ohan V, Olney C, Ormond D, Oszlanczi A, Pang YF, Pardubska B, Park N, Parmar A, Patel G, Payne M, Peacock S, Petersen A, Plowman D, Preston T, Quail M, 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 EM, Roopra D, Rose M, Rudd L, Sadri R, Salmon N, Saul D, Schwach F, Seekings P, Simms A, Sinnott M, Sivadasan S, Siwek B, Sizer D, Skeldon K, Skelton J, Slater-Tunstill J, Sloper L, Smerdon N, Smith C, Smith C, Smith J, Smith K, Smith M, Smith S, Smith T, Sneade L, Soria CD, Sousa C, Souster E, Sparkes A, Spencer-Chapman M, Squares J, Stanley R, 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, Taylor S, Thompson S, Thompson M, Thomson M, Thomson N, Thurston S, Toombs D, Topping B, Tovar-Corona J, Ungureanu D, Uphill J, Urbanova J, Van PJ, 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, Widaa S, Williams M, Wilson M, Wright S, Duncan LM, Carabelli AM, Kenyon JC, Lever AM, De Marco A, Saliba C, Culap K, Cameroni E, Matheson NJ, Piccoli L, Corti D, James LC, Robertson DL, Bailey D, Gupta RK & The COVID-19 Genomics UK (COG-UK) Consortium(2021) Cell Reports 35, 109292.
We report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike ?H69/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 ?H69/V70 itself is not an antibody evasion mechanism, it increases infectivity associated with enhanced incorporation of cleaved spike into virions. ?H69/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 ?H69/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 ?H69/V70. Therefore, as ?H69/V70 compensates for immune escape mutations that impair infectivity, continued surveillance for deletions with functional effects is warranted. © 2021 The Author(s)