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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Recurrent emergence of SARS-CoV-2 spike deletion H69/V70 and its role in the Alpha variant B.1.1.7
Cell Reports, Volume 35, No. 13, Article 109292, Year 2021
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Description
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. © 2021 The Author(s)
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC8185188/bin/mmc1.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC8185188/bin/mmc2.pdf
Authors & Co-Authors
Meng, Bo
United Kingdom, Cambridge
University of Cambridge
Kemp, Steven A.
United Kingdom, Cambridge
University of Cambridge
United Kingdom, London
University College London
Papa, Guido
United Kingdom, Cambridge
The Medical Research Council Laboratory of Molecular Biology
Datir, Rawlings P.
United Kingdom, Cambridge
University of Cambridge
Ferreira, Isabella A.T.M.
United Kingdom, Cambridge
University of Cambridge
Harvey, William T.
United Kingdom, Glasgow
University of Glasgow
United Kingdom, Glasgow
Mrc-university of Glasgow Centre for Virus Research
Lytras, Spyros
United Kingdom, Glasgow
Mrc-university of Glasgow Centre for Virus Research
Collier, Dami Aderonke
United Kingdom, Cambridge
University of Cambridge
United Kingdom, London
University College London
Mlčochová, Petra
United Kingdom, Cambridge
University of Cambridge
Loman, Nicholas James
Unknown Affiliation
Connor, Thomas R.
Unknown Affiliation
Golubchik, Tanya
Unknown Affiliation
Bonsall, David G.
Unknown Affiliation
Török, Mili Estee
Unknown Affiliation
Jackson, David K.
Unknown Affiliation
Hamilton, William L.
Unknown Affiliation
Snell, Luke Blagdon
Unknown Affiliation
Moore, Catherine
Unknown Affiliation
Harrison, Ewan M.
Unknown Affiliation
Gonçalves, Sonia Morgado
Unknown Affiliation
Loose, Matthew W.
Unknown Affiliation
Moses, Samuel E.
Unknown Affiliation
Amato, Roberto
Unknown Affiliation
Nicholls, Sam M.
Unknown Affiliation
Bull, Matthew J.
Unknown Affiliation
Smith, Darren Lee
Unknown Affiliation
Barrett, Jeffrey C.
Unknown Affiliation
Aanensen, David Michael
Unknown Affiliation
Curran, Martin David
Unknown Affiliation
Parmar, Surendra A.
Unknown Affiliation
Aggarwal, Dinesh
Unknown Affiliation
Shepherd, James G.
Unknown Affiliation
Parker, Matthew D.
Unknown Affiliation
Underwood, Anthony P.
Unknown Affiliation
Templeton, Kate E.
Unknown Affiliation
Sillitoe, John
Unknown Affiliation
de Silva, Thushan I.
Unknown Affiliation
Wang, Dennis Y.Q.
Unknown Affiliation
Kwiatkowski, Dominic P.
Unknown Affiliation
Rambaut, Andrew
Unknown Affiliation
O'Grady, Justin
Unknown Affiliation
Cottrell, Simon L.
Unknown Affiliation
Holden, Matthew T.G.
Unknown Affiliation
Thomson, Emma C.
Unknown Affiliation
Osman, Husam Kamal Eldin
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Andersson, Monique I. Ingrid
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Lawniczak, Mara K.N.
Unknown Affiliation
Chand, Meera A.
Unknown Affiliation
Darby, Alistair Charles
Unknown Affiliation
Hiscox, Julian A.
Unknown Affiliation
Paterson, Steve C.
Unknown Affiliation
Martincorena, Iñigo
Unknown Affiliation
Volz, Erik M.
Unknown Affiliation
Page, Andrew J.
Unknown Affiliation
Pybus, Oliver George
Unknown Affiliation
Bassett, Andrew Roger
Unknown Affiliation
Shah, Rajiv N.
Unknown Affiliation
Taha, Yusri A.
Unknown Affiliation
McHugh, Martin P.
Unknown Affiliation
Nelson, Andrew T.
Unknown Affiliation
Young, Gregory R.
Unknown Affiliation
McCann, Clare M.
Unknown Affiliation
Temperton, Ben
Unknown Affiliation
Roy, Sunando
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Price, Anna
Unknown Affiliation
Rooke, Stefan
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de Cesare, Mariateresa
Unknown Affiliation
Hosmillo, Myra D.T.
Unknown Affiliation
O'Toole, Áine Niamh
Unknown Affiliation
Hesketh, Andrew R.
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Plessis, Louis Du
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Ruis, Christopher
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Bourgeois, Yann X.C.
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Edgeworth, Jonathan D.
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Breuer, Judith M.
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Todd, John A.
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Fraser, Christophe
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Buck, David
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Kay, Gemma Louise
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Peacock, Sharon J.
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Robinson, Esther R.
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McNally, Alan
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Muir, Peter
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Dervisevic, Samir
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Meader, Emma Jane
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Park, Naomi R.
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Jeffries, Aaron Richard
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da Silva Filipe, Ana
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Williams, Chris J.A.
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Masoli, Jane A.H.
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Knight, Bridget Ann
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Jones, Christopher R.
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Casey, Anna L.
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Bosworth, Andrew
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Jones, Kate E.
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Halstead, Fenella D.
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Iturriza-Gómara, Miren
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Lucaci, Anita O.
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Cox, Alison
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Harris, Kathryn Ann
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Haque, Tanzina J.
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Warne, Ben
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Tonkin-Hill, Gerry Q.
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Alam, Mohammad Tauqeer
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Orton, Richard J.
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Hughes, Joseph T.
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Vattipally, Sreenu B.
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Ragonnet-Cronin, Manon L.
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Nascimento, Fabrícia F.
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Jorgensen, David
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Geidelberg, Lily
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Zarebski, Alexander Eugene
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Raghwani, Jayna
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Kraemer, Moritz U.G.
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Southgate, Joel Alexander
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Lindsey, Benjamin B.
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de Oliveira Martins, Leonardo
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Ellaby, Nicholas A.F.
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Hartman, Hassan B.
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Ledesma, Juan
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Twohig, Katherine A.
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Brown, Paul E.
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Tong, Lily
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Nichols, Jenna
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Nomikou, Kyriaki
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Rainbow, Lucille
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Wierzbicki, Claudia
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O’Brien, Sarah J.
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Ariani, Cristina Valente
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Bala, Sendu
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Barrett, Jeffrey C.
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Beale, Mathew A.
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Bellis, Katherine L.
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Berger, Duncan J.
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Berriman, Matthew
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Bevan, Paul
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Buddenborg, Sarah Kay
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Cagan, Alex T.J.
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Clapham, Peter
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Corton, Craig H.
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Dabrowska, Monika H.
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Dougan, Gordon J.
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Ellis, Peter D.
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Fraser, Audrey E.
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Gray, Emma K.
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Hernández-Koutoucheva, Anastasia
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Keatley, Jon Paul
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Korlević, Petra
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Langford, Cordelia F.
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Lindsay, Sarah J.
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Maddison, Mark
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Mayho, Matthew
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O'Meara, Sarah
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Ormond, Doug
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Peacock, Sharon J.
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Rance, Richard
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Richardson, Matthew
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Schwach, Frank
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Steed, Claire
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Swiatkowska, Agnieszka
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Thomson, Nicholas Robert
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Thurston, Scott A.J.
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Vancollie, Valerie E.
Unknown Affiliation
Walker, Danielle Carey
Unknown Affiliation
Walker, Matthew R.
Unknown Affiliation
Widaa, Sara
Unknown Affiliation
Carabelli, Alessandro M.
United Kingdom, Cambridge
University of Cambridge
Lever, Andrew Michael Lindsay
United Kingdom, Cambridge
University of Cambridge
Singapore, Singapore City
National University of Singapore
Cameroni, Elisabetta
United States, San Francisco
Vir Biotechnology, Inc.
Matheson, Nicholas J.
United Kingdom, Cambridge
University of Cambridge
United Kingdom, Bristol
Nhs Blood and Transplant
Piccoli, Luca
United States, San Francisco
Vir Biotechnology, Inc.
Corti, Davide
United States, San Francisco
Vir Biotechnology, Inc.
James, Leo C.
United Kingdom, Cambridge
The Medical Research Council Laboratory of Molecular Biology
Robertson, David L.
United Kingdom, Glasgow
Mrc-university of Glasgow Centre for Virus Research
Bailey, Dalan S.
United Kingdom, Surrey
The Pirbright Institute
Gupta, Ravindra K.
United Kingdom, Cambridge
University of Cambridge
South Africa, Durban
Africa Health Research Institute
Statistics
Citations: 331
Authors: 302
Affiliations: 10
Identifiers
Doi:
10.1016/j.celrep.2021.109292
ISSN:
22111247
Research Areas
Covid