Details

Autor(en) / Beteiligte

• Curran, Martin D.
• Roy, Sunando
• Shaaban, Sharif
• de Cesare, Mariateresa
• Stark, Richard
• Palmer, Steve
• Jeffries, Aaron R.
• da Silva Filipe, Ana
• Davis, Thomas
• Collins, Jennifer
• Williams, Thomas
• Haldenby, Sam T.
• Cook, Kate
• Davies, Robert
• Kay, Sally
• Poplawski, Radoslaw
• Reynolds, Nicola
• Moll, Robin J.
• Thornton, Alicia
• Gatica-Wilcox, Bree
• Louka, Stavroula F.
• Kraemer, Moritz U.G.
• Freeman, Timothy M.
• Abudahab, Khalil
• Menegazzo, Mirko
• Mason, Jenifer
• Holmes, Alison
• Curran, Tanya
• Mookerjee, Siddharth
• Munn, Robert
• Davies, Alisha
• Smith, Nikki
• Cormie, Claire
• Lo, Stephanie
• Auckland, Cressida
• Mollett, Guy
• Harper, Katherine L.
• Bonner, Stephen
• Padgett, Debra
• Burton-Fanning, Shirelle
• Bedford, Luke
• Coupland, Lindsay
• Wright, Victoria
• Ball, Jonathan
• Boswell, Tim
• Duckworth, Nichola
• Williams, Rebecca
• Cogger, Benjamin J.
• Farr, Ben W.
• Thurston, Scott A.J.
• Bronner, Iraad F.
• Aigrain, Louise
• Gallagher, Michael D.
• Miah, Shahjahan
• Ramsay, Mary
• Schaefer, Ulf
• Manesis, Nikos
• Allara, Elias
• Nichols, Jenna
• Vamos, Edith E.
• Hughes, Margaret
• Wilson, Harry D.
• Wilson, Rebekah E.
• Thompson, Thomas
• O’Brien, Sarah
• Rudder, Steven
• McCluggage, Kathryn
• Bonfield, James
• Liddle, Jennifier
• Rowe, Will
• Bevan, Paul
• Clark, Richard
• Cutts, Tim
• Densem, Aiden
• Dodd, David
• Griffiths, Coline
• Kay, Keely
• Lensing, Stefanie
• Lewis-Wade, Amanah
• Mamun, Irfan
• Martin, Matt
• McClintock, Jo
• Nathwani, Claire
• Nicholson, Jon
• Patel, Gaurang
• Petersen, Arabella
• Reynolds, Joe
• Rudd, Luke
• Sadri, Ramin
• Sizer, Dale
• Soria, Carmen Diaz
• Sousa, Catarina
• Squares, Janet
• Stickland, Tim
• Still, Ian
• Symons, Edward
• Uphill, James
• Van, Philip Jansen
• Voak, Paul
• Corti, Davide

Titel

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

Ist Teil von

• Cell reports (Cambridge), 2021-06, Vol.35 (13), p.109292, Article 109292

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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. [Display omitted] •Spike ΔH69/V70 does not confer escape from antibodies•Spike ΔH69/V70 increases cleaved S2 and spike infectivity•B.1.1.7 requires ΔH69/V70 for efficient cleaved spike incorporation and infectivity•B.1.1.7 spike requires ΔH69/V70 for rapid syncytium formation Meng et al. report that the SARS-CoV-2 spike ΔH69/V70 has arisen multiple times. The deletion increases entry efficiency associated with increased cleaved spike in virions and can compensate for loss of infectivity. The B.1.1.7 spike requires ΔH69/V70 for efficient cell entry and cell-cell fusion activity.