Recurrent emergence of SARS-CoV-2 spike deletion H69/V70 and its role in the Alpha variant B.1.1.7

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; 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; Sally Forrest; Adam Westhorpe; Jonathan Ball

doi:10.1016/j.celrep.2021.109292

Recurrent emergence of SARS-CoV-2 spike deletion H69/V70 and its role in the Alpha variant B.1.1.7

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, Samuel C. Robson, Nicholas J. Loman, Thomas R. Connor, Tanya Golubchik, Rocio T. Martinez Nunez, Catherine Ludden, Sally CordenIan 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, Sally Forrest, Adam Westhorpe, Jonathan Ball

Liverpool School of Tropical Medicine

Research output: Contribution to journal › Article › peer-review

397 Citations (Scopus)

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.

Original language	English
Article number	109292
Journal	Cell Reports
Volume	35
Issue number	13
DOIs	https://doi.org/10.1016/j.celrep.2021.109292
Publication status	Published - 29 Jun 2021

Keywords

Alpha variant
antibody escape
B.1.1.7
COVID-19
deletion
infectivity
neutralizing antibodies
resistance
SARS-CoV-2
spike mutation

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Meng, B., Kemp, S. A., Papa, G., Datir, R., Ferreira, I. A. T. M., Marelli, S., Harvey, W. T., Lytras, S., Mohamed, A., Gallo, G., Thakur, N., Collier, D. A., Mlcochova, P., Robson, S. C., Loman, N. J., Connor, T. R., Golubchik, T., Martinez Nunez, R. T., Ludden, C., ... Ball, J. (2021). Recurrent emergence of SARS-CoV-2 spike deletion H69/V70 and its role in the Alpha variant B.1.1.7. Cell Reports, 35(13), Article 109292. https://doi.org/10.1016/j.celrep.2021.109292

@article{1aada54bc0374444898c10e5dffaec04,

title = "Recurrent emergence of SARS-CoV-2 spike deletion H69/V70 and its role in the Alpha variant B.1.1.7",

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.",

keywords = "Alpha variant, antibody escape, B.1.1.7, COVID-19, deletion, infectivity, neutralizing antibodies, resistance, SARS-CoV-2, spike mutation",

author = "Bo Meng and Kemp, \{Steven A.\} and Guido Papa and Rawlings Datir and Ferreira, \{Isabella A.T.M.\} and Sara Marelli and Harvey, \{William T.\} and Spyros Lytras and Ahmed Mohamed and Giulia Gallo and Nazia Thakur and Collier, \{Dami A.\} and Petra Mlcochova and Robson, \{Samuel C.\} and Loman, \{Nicholas J.\} and Connor, \{Thomas R.\} and Tanya Golubchik and \{Martinez Nunez\}, \{Rocio T.\} and Catherine Ludden and Sally Corden and Ian Johnston and David Bonsall and Smith, \{Colin P.\} and Awan, \{Ali R.\} and Giselda Bucca and Torok, \{M. Estee\} and Kordo Saeed and Prieto, \{Jacqui A.\} and Jackson, \{David K.\} and Hamilton, \{William L.\} and Snell, \{Luke B.\} and Catherine Moore and Harrison, \{Ewan M.\} and Sonia Goncalves and Fairley, \{Derek J.\} and Loose, \{Matthew W.\} and Joanne Watkins and Rich Livett and Samuel Moses and Roberto Amato and Sam Nicholls and Matthew Bull and Smith, \{Darren L.\} and Jeff Barrett and Aanensen, \{David M.\} and Curran, \{Martin D.\} and Surendra Parmar and Sally Forrest and Adam Westhorpe and Jonathan Ball",

year = "2021",

month = jun,

day = "29",

doi = "10.1016/j.celrep.2021.109292",

language = "English",

volume = "35",

journal = "Cell Reports",

issn = "2639-1856",

publisher = "Elsevier B.V.",

number = "13",

}

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, Forrest, S, Westhorpe, A & Ball, J 2021, 'Recurrent emergence of SARS-CoV-2 spike deletion H69/V70 and its role in the Alpha variant B.1.1.7', Cell Reports, vol. 35, no. 13, 109292. https://doi.org/10.1016/j.celrep.2021.109292

TY - JOUR

T1 - Recurrent emergence of SARS-CoV-2 spike deletion H69/V70 and its role in the Alpha variant B.1.1.7

AU - Meng, Bo

AU - Kemp, Steven A.

AU - Papa, Guido

AU - Datir, Rawlings

AU - Ferreira, Isabella A.T.M.

AU - Marelli, Sara

AU - Harvey, William T.

AU - Lytras, Spyros

AU - Mohamed, Ahmed

AU - Gallo, Giulia

AU - Thakur, Nazia

AU - Collier, Dami A.

AU - Mlcochova, Petra

AU - Robson, Samuel C.

AU - Loman, Nicholas J.

AU - Connor, Thomas R.

AU - Golubchik, Tanya

AU - Martinez Nunez, Rocio T.

AU - Ludden, Catherine

AU - Corden, Sally

AU - Johnston, Ian

AU - Bonsall, David

AU - Smith, Colin P.

AU - Awan, Ali R.

AU - Bucca, Giselda

AU - Torok, M. Estee

AU - Saeed, Kordo

AU - Prieto, Jacqui A.

AU - Jackson, David K.

AU - Hamilton, William L.

AU - Snell, Luke B.

AU - Moore, Catherine

AU - Harrison, Ewan M.

AU - Goncalves, Sonia

AU - Fairley, Derek J.

AU - Loose, Matthew W.

AU - Watkins, Joanne

AU - Livett, Rich

AU - Moses, Samuel

AU - Amato, Roberto

AU - Nicholls, Sam

AU - Bull, Matthew

AU - Smith, Darren L.

AU - Barrett, Jeff

AU - Aanensen, David M.

AU - Curran, Martin D.

AU - Parmar, Surendra

AU - Forrest, Sally

AU - Westhorpe, Adam

AU - Ball, Jonathan

PY - 2021/6/29

Y1 - 2021/6/29

N2 - 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.

AB - 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.

KW - Alpha variant

KW - antibody escape

KW - B.1.1.7

KW - COVID-19

KW - deletion

KW - infectivity

KW - neutralizing antibodies

KW - resistance

KW - SARS-CoV-2

KW - spike mutation

U2 - 10.1016/j.celrep.2021.109292

DO - 10.1016/j.celrep.2021.109292

M3 - Article

SN - 2639-1856

VL - 35

JO - Cell Reports

JF - Cell Reports

IS - 13

M1 - 109292

ER -

Recurrent emergence of SARS-CoV-2 spike deletion H69/V70 and its role in the Alpha variant B.1.1.7

Abstract

Keywords

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